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    Oxazolidinone Antibiotics

    DEA CLASS

    Rx

    DESCRIPTION

    Synthetic oxazolidinone antibiotic
    Indicated for treatment of bacterial pneumonia, skin and skin structure infections, and for vancomycin-resistant enterococcal (VRE) infections, including infections due to susceptible organisms which are complicated by bacteremia
    Inhibits MAO and may cause drug interactions with adrenergic and serotonergic drugs

    COMMON BRAND NAMES

    Zyvox

    HOW SUPPLIED

    Linezolid/Zyvox Intravenous Inj Sol: 1mL, 2mg
    Linezolid/Zyvox Oral Pwd F/Recon: 5mL, 100mg
    Linezolid/Zyvox Oral Tab: 600mg

    DOSAGE & INDICATIONS

    For the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia, and nosocomial pneumonia.
    For the treatment of nosocomial pneumonia.
    Oral dosage
    Adults

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] [61215] Guidelines recommend empiric linezolid use in patients with risk factors for MRSA. Oral therapy is not addressed in guidelines, but de-escalation in general is recommended.[61215]

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for at least 7 days.[28599] [46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days.[28599] [46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response.[28599] [46693]

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] [61215] Guidelines recommend empiric linezolid use in patients with risk factors for MRSA.[61215]

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for at least 7 days.[28599] [46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days.[28599] [46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response.[28599] [46693]

    For the treatment of community-acquired pneumonia (CAP), including cases with concurrent bacteremia.
    Oral dosage
    Adults

    600 mg PO every 12 hours for at least 7 days as part of combination therapy for hospitalized patients with prior respiratory isolation of MRSA or risk factors for MRSA and recent hospitalization with parenteral antibiotic use.[28599] [34362] [46693] [64669]

    Adolescents

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693] In HIV-infected patients, linezolid is recommended as part of combination therapy for patients with risk factors for MRSA.[34362]

    Children 12 years

    600 mg PO every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for at least 7 days. May consider 10 mg/kg/dose PO every 8 hours if suboptimal clinical response.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for at least 7 days as part of combination therapy for hospitalized patients with prior respiratory isolation of MRSA or risk factors for MRSA and recent hospitalization with parenteral antibiotic use.[28599] [34362] [46693] [64669]

    Adolescents

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693] In HIV-infected patients, linezolid is recommended as part of combination therapy for patients with risk factors for MRSA.[34362]

    Children 12 years

    600 mg IV every 12 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for at least 7 days.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    Premature Neonates less than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for at least 7 days. May consider 10 mg/kg/dose IV every 8 hours if suboptimal clinical response.[28599] [46693] Guidelines recommend linezolid as empiric therapy for ICU patients with suspected MRSA or for any patient with documented MRSA.[46693]

    For the treatment of skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, diabetic foot ulcer, leg ulcer, and surgical incision site infections.
    For the treatment of unspecified complicated skin infections.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 7 to 14 days.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 7 to 14 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours for 7 to 14 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 7 to 14 days.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 7 to 14 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for 7 to 14 days. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 7 to 14 days.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 7 to 14 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours for 7 to 14 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for 7 to 14 days.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for 7 to 14 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for 7 to 14 days. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response.

    For the treatment of uncomplicated, nonpurulent skin infections, such as cellulitis and erysipelas.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 5 to 14 days. The FDA-approved dose is 400 mg PO every 12 hours for 10 to 14 days.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 5 to 14 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 to 12 hours for 5 to 14 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 5 to 14 days.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 5 to 14 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours for 5 to 14 days. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.

    Intravenous dosage†
    Adults

    600 mg IV every 12 hours for 5 to 14 days.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 5 to 14 days.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 to 12 hours for 5 to 14 days.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for 5 to 14 days.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for 5 to 14 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours for 5 to 14 days. Consideration may be given to the use of 10 mg/kg/dose IV every 8 hours in those with a sub-optimal clinical response.

    For the treatment of surgical incision site infections.
    Oral dosage
    Adults

    600 mg PO every 12 hours in patients with prior methicillin-resistant S. aureus infection, recent hospitalization, or recent antibiotic exposure.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours in patients with prior methicillin-resistant S. aureus infection, recent hospitalization, or recent antibiotic exposure.

    For the treatment of diabetic foot ulcer.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 7 to 14 days for mild infections in patients at high risk for methicillin-resistant S. aureus (MRSA) or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 7 to 14 days for mild infections in patients at high risk for methicillin-resistant S. aureus (MRSA) or moderate or severe infections in patients with risk factors for MRSA. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

    For the treatment of necrotizing infections of the skin, fascia, and muscle.
    Oral dosage
    Adults

    600 mg PO every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections. Consideration may be given to the use of 10 mg/kg/dose PO every 8 hours in those with a sub-optimal clinical response.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours as a part of broad empiric therapy or in patients with severe penicillin hypersensitivity and S. aureus or Streptococcus infections. Consideration may be given to the use of 10 mg/kg/dose IV every 8 hours in those with a sub-optimal clinical response.

    For the treatment of leg ulcer.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 7 to 14 days.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 7 to 14 days.

    For the treatment of drug-resistant tuberculosis infection as part of combination therapy.
    For the general treatment of drug-resistant tuberculosis infection† in combination with other antitubercular agents.
    Oral dosage
    Adults

    600 mg PO once daily.

    Children and Adolescents 10 to 17 years

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily.

    Children 1 to 9 years weighing more than 23 kg

    10 mg/kg/dose (Max: 600 mg/dose) PO once daily.

    Children 1 to 9 years weighing 10 to 23 kg

    12 mg/kg/dose PO once daily or 10 mg/kg/dose PO twice daily.

    Children 1 to 4 years weighing less than 10 kg

    15 mg/kg/dose PO once daily or 10 mg/kg/dose PO twice daily.

    Infants weighing 10 kg or more

    12 mg/kg/dose PO once daily or 10 mg/kg/dose PO twice daily.

    Infants weighing less than 10 kg

    15 mg/kg/dose PO once daily or 10 mg/kg/dose PO twice daily.

    Intravenous dosage
    Adults

    600 mg IV once daily.

    Children and Adolescents 10 to 17 years

    10 mg/kg/dose (Max: 600 mg/dose) IV once daily.

    Children 1 to 9 years weighing more than 23 kg

    10 mg/kg/dose (Max: 600 mg/dose) IV once daily.

    Children 1 to 9 years weighing 10 to 23 kg

    12 mg/kg/dose IV once daily or 10 mg/kg/dose IV twice daily.

    Children 1 to 4 years weighing less than 10 kg

    15 mg/kg/dose IV once daily or 10 mg/kg/dose IV twice daily.

    Infants weighing 10 kg or more

    12 mg/kg/dose IV once daily or 10 mg/kg/dose IV twice daily.

    Infants weighing less than 10 kg

    15 mg/kg/dose IV once daily or 10 mg/kg/dose IV twice daily.

    For the treatment of pulmonary extensively drug-resistant tuberculosis infection (XDR-TB) or treatment-intolerant or nonresponsive multidrug-resistant tuberculosis infection (MDR-TB) as part of a combination regimen with bedaquiline and pretomanid.

    NOTE: Safety and effectiveness have not been established for use in combination with drugs other than bedaquiline and pretomanid.[64561]
    NOTE: This combination regimen is not indicated for the treatment of drug-sensitive tuberculosis, latent M. tuberculosis infection, extra-pulmonary M. tuberculosis infection, or MDR-TB that is not treatment-intolerant or nonresponsive to standard therapy.[64561]
    Oral dosage
    Adults

    1,200 mg PO once daily for 26 weeks. May extend dosing of the combination regimen beyond 26 weeks if needed. If pretomanid or bedaquiline is discontinued, discontinue the entire combination regimen. If linezolid is permanently discontinued during the initial 4 consecutive weeks of treatment, discontinue the entire combination regimen. If linezolid is discontinued after the initial 4 weeks of consecutive treatment, continue pretomanid and bedaquiline therapy.[64561]

    For the treatment of sepsis† or bacteremia due to vancomycin-resistant enterococci (VRE) or methicillin-resistant Staphylococcus aureus (MRSA)†.
    For the treatment of infections due to vancomycin-resistant enterococci (VRE) (i.e., E. faecium; E. faecalis), including those infections with concurrent bacteremia or sepsis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 14 to 28 days. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Infants and Children 1 to 11 years

    10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose IV every 8 hours for 14 to 28 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.

    Oral dosage
    Adults

    600 mg PO every 12 hours for 14 to 28 days. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Infants and Children 1 to 11 years

    10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours for 14 to 28 days.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    10 mg/kg/dose PO every 8 hours for 14 to 28 days.

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response. The total course of therapy should be 14 to 28 days in length.

    For the treatment of persistent Staphylococcus aureus (MRSA) bacteremia† with vancomycin failure and sepsis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours with high dose daptomycin for at least 2 weeks for persistent bacteremia. If reduced susceptibility to vancomycin and daptomycin are present, linezolid 600 mg IV every 12 hours may be administered as a single agent or in combination with other antibiotics. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Oral dosage
    Adults

    600 mg PO every 12 hours with high dose daptomycin for at least 2 weeks for persistent bacteremia. If reduced susceptibility to vancomycin and daptomycin are present, linezolid 600 mg PO every 12 hours may be administered as a single agent or in combination with other antibiotics. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    For the treatment of neonatal methicillin-resistant Staphylococcus aureus (MRSA) sepsis†.
    Intravenous dosage
    Neonates 34 weeks gestation and older

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose IV every 8 hours.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose IV every 8 hours.[28599]

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose IV every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response.[28599]

    Oral dosage
    Neonates 34 weeks gestation and older

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose PO every 8 hours.[28599] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from the scope of the Surviving Sepsis Campaign guidelines.[64985]

    Premature Neonates younger than 34 weeks gestation and older than 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose PO every 8 hours.[28599]

    Premature Neonates younger than 34 weeks gestation and 0 to 6 days

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends linezolid as an option for patients with non-endovascular infections; however, dosing is not specified as experience with linezolid in MRSA neonatal sepsis is limited.[46693] The dosage used for other indications is 10 mg/kg/dose PO every 12 hours initially. Consideration may be given to the use of 10 mg/kg/dose every 8 hours in those with a sub-optimal clinical response.[28599]

    For the treatment of MRSA-associated bone and joint infections†, including osteomyelitis† and septic/infectious arthritis†, or an orthopedic device-related infection†.
    For the treatment of osteomyelitis†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours. Rifampin 600 mg PO daily or 300 to 450 mg PO twice daily may be added; however, in patients with concurrent bacteremia, rifampin should be added after the clearance of the bacteremia. A minimum duration of 8 weeks is recommended; an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus either sulfamethoxazole/trimethoprim, doxycycline, minocycline, clindamycin, or a fluoroquinolone may be necessary.

    Children and Adolescents 12 to 17 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 4 to 6 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 4 to 6 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 4 to 6 weeks.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours. Rifampin 600 mg PO daily or 300 to 450 mg PO twice daily may be added; however, in patients with concurrent bacteremia, rifampin should be added after the clearance of the bacteremia. A minimum duration of 8 weeks is recommended; an additional 1 to 3 months (or longer for chronic infection or if no debridement performed) of oral rifampin plus either sulfamethoxazole/trimethoprim, doxycycline, minocycline, clindamycin, or a fluoroquinolone may be necessary.

    Children and Adolescents 12 to 17 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 4 to 6 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 4 to 6 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 4 to 6 weeks.

    For the treatment of septic arthritis†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 3 to 4 weeks.

    Children and Adolescents 12 to 17 years

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours for 3 to 4 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) for 3 to 4 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours for 3 to 4 weeks.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 3 to 4 weeks.

    Children and Adolescents 12 to 17 years

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours for 3 to 4 weeks.

    Infants and Children 1 to 11 years

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) for 3 to 4 weeks.

    Neonates

    As an alternative to vancomycin, the Infectious Diseases Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours for 3 to 4 weeks.

    For the treatment of prosthetic joint infections†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours for 2 weeks in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus a fluoroquinolone, sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin) should start after the completion of IV therapy and continue for 3 months for hip infections or for 6 months for knee infections.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours for 2 weeks in patients with early-onset (less than 2 months after surgery) or acute hematogenous prosthetic joint infections involving a stable implant with short duration (3 weeks or less) of symptoms and debridement (but device retention). Additional oral therapy (rifampin plus a fluoroquinolone, sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin) should continue for 3 months for hip infections or for 6 months for knee infections.

    For the treatment of spinal implant infections†.
    Intravenous dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg IV every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy (sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin +/- rifampin, or a fluoroquinolone plus rifampin) should follow parenteral therapy; however, the optimal duration of parenteral and/or oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    Oral dosage
    Adults

    The Infectious Diseases Society of America (IDSA) recommends 600 mg PO every 12 hours plus rifampin 600 mg PO daily or 300 to 450 mg PO every 12 hours in patients with early-onset spinal implant infections (30 days or less after surgery) or implants in an actively infected site. Prolonged oral therapy (sulfamethoxazole; trimethoprim, a tetracycline, or clindamycin +/- rifampin, or a fluoroquinolone plus rifampin) should follow; however, the optimal duration of oral therapy is unclear. Oral therapy should be continued until spine fusion has occurred. Long term oral suppressive therapy may be considered in select cases, especially if device removal is not possible.

    For the treatment of central nervous system infections†, including meningitis†, ventriculitis†, brain abscess†, subdural empyema†, spinal epidural abscess†, and septic thrombosis of the cavernous or dural venous sinus†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours as an alternative to vancomycin is recommended by the Infectious Diseases Society of America (IDSA). The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Children and Adolescents 12 to 17 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg IV every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants and Children 1 to 11 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose IV every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Oral dosage
    Adults

    600 mg PO every 12 hours as an alternative to vancomycin is recommended by the Infectious Diseases Society of America (IDSA). The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Children and Adolescents 12 to 17 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. As an alternative to vancomycin, the Infectious Disease Society of America (IDSA) recommends 600 mg PO every 12 hours. The recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Infants and Children 1 to 11 years

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in several case reports (n = 8) in infants and children with VP shunt infections due to vancomycin-resistant enterococci. In addition, the Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose) as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    Neonates

    The manufacturer warns against use of linezolid for the empiric treatment of CNS infections in pediatric patients. Pediatric patients with ventriculoperitoneal (VP) shunts obtained variable cerebrospinal fluid (CSF) linezolid concentrations, and therapeutic concentrations were not consistently achieved or maintained in the CSF in 2 multiple-dose, pharmacokinetic studies. However, linezolid has been used successfully in a case report in a neonate (6 weeks old, born at 35-weeks gestational age) with VP shunt infection due to vancomycin-resistant enterococci. A higher linezolid dose (12 mg/kg/dose every 8 hours for 2 weeks after 3 weeks of 10 mg/kg/dose every 8 hours) was used with good outcomes; bone marrow suppression was not observed during therapy. The Infectious Disease Society of America (IDSA) recommends 10 mg/kg/dose PO every 8 hours as an alternative to vancomycin. Per IDSA, the recommended duration of treatment is 2 weeks for meningitis and 4 to 6 weeks for brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of the cavernous or dural venous sinus.

    For the treatment of febrile neutropenia†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours has been studied. Guidelines suggest linezolid as an option in patients with MRSA or VRE. In a double-blind, randomized controlled trial, IV linezolid was equivalent to vancomyin in patients with suspected or confirmed gram-positive infection.

    Oral dosage
    Adults

    600 mg PO every 12 hours. Guidelines suggest linezolid as an option in patients with MRSA or VRE. In a double-blind, randomized controlled trial, IV linezolid was equivalent to vancomyin in patients with suspected or confirmed gram-positive infection.

    For the treatment of infective endocarditis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours for more than 6 weeks for endocarditis caused by Enterococcus sp. resistant to penicillin, aminoglycosides, and vancomycin.

    Children and Adolescents 12 to 17 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg IV every 12 hours.

    Infants and Children 1 to 11 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose).

    Neonates

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with endocarditis. Previous guidelines recommended 10 mg/kg/dose IV every 8 hours.

    Oral dosage
    Adults

    600 mg PO every 12 hours for more than 6 weeks for endocarditis caused by Enterococcus sp. resistant to penicillin, aminoglycosides, and vancomycin.

    Children and Adolescents 12 to 17 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 600 mg PO every 12 hours.

    Infants and Children 1 to 11 years

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for pediatric patients with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose).

    Neonates

    Current guidelines do not provide a linezolid dose and recommend infectious disease consultation as the standard of care for neonates with enterococcal endocarditis. Previous guidelines recommended 10 mg/kg/dose PO every 8 hours.

    For the treatment of systemic anthrax† infection.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is a preferred therapy in systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Children and Adolescents 12 to 17 years

    15 mg/kg/dose IV every 12 hours (Max: 600 mg/dose) in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam/glycopeptide (i.e., meropenem, imipenem; cilastatin, vancomycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Infants and Children 1 to 11 years

    10 mg/kg/dose IV every 8 hours (Max: 600 mg/dose) in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam/glycopeptide (i.e., meropenem, imipenem; cilastatin, vancomycin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Neonates 35 weeks gestation and older

    10 mg/kg/dose IV every 8 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Premature Neonates 32 to 34 weeks gestation and older than 7 days

    10 mg/kg/dose IV every 8 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Premature Neonates 32 to 34 weeks gestation and 0 to 7 days of age

    10 mg/kg/dose IV every 12 hours in combination with appropriate antimicrobial therapy. Linezolid, in combination with a fluoroquinolone and beta lactam (i.e., meropenem, imipenem; cilastatin), is the preferred therapy for the treatment of systemic anthrax in which meningitis cannot be excluded. Linezolid, in combination with a bactericidal antimicrobial (i.e., ciprofloxacin, meropenem), is an alternative therapy for systemic anthrax infection without CNS involvement. For systemic infection in which meningitis cannot be excluded, treatment should continue for at least 2 to 3 weeks or until clinical criteria for improvement are met. For systemic infection without CNS involvement, treatment should continue for at least 14 days or until clinical criteria for improvement are met. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.

    Oral dosage
    Children and Adolescents 12 to 17 years

    15 mg/kg/dose PO every 12 hours (Max: 600 mg/dose). Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Infants and Children 1 to 11 years

    10 mg/kg/dose PO every 8 hours (Max: 600 mg/dose). Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Neonates 35 weeks gestation and older

    10 mg/kg/dose PO every 8 hours. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Premature Neonates 32 to 34 weeks gestation and older than 7 days

    10 mg/kg/dose PO every 8 hours. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    Premature Neonates 32 to 34 weeks gestation and 0 to 7 days of age

    10 mg/kg/dose PO every 12 hours in combination with a fluoroquinolone. Linezolid, in combination with a fluoroquinolone, is recommended as an alternative oral follow-up combination therapy for severe anthrax (non-CNS infection). Treatment should be continued to complete a course of at least 14 days. Prophylaxis to complete an antimicrobial course of up to 60 days may be required.

    For the treatment of intraabdominal infections†, including peritonitis†, appendicitis, intraabdominal abscess†, spontaneous bacterial peritonitis†, peritoneal dialysis-related peritonitis†, and peritoneal dialysis catheter-related infection†.
    For the treatment of complicated healthcare-acquired or hospital-acquired intraabdominal infections† with adequate source control.
    Oral dosage
    Adults

    600 mg PO every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 400 mg/dose) PO every 8 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days.

    Premature Neonates younger than 34 weeks gestation and older than 7 days

    10 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days.

    Premature Neonates less than 34 weeks gestation and 0 to 7 days

    10 mg/kg/dose PO every 12 hours as part of combination therapy for 7 to 10 days.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Infants and Children 1 to 11 years

    10 mg/kg/dose (Max: 400 mg/dose) IV every 8 hours as part of combination therapy for 3 to 7 days as an alternative. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Neonates 34 weeks gestation and older

    10 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days.

    Premature Neonates younger than 34 weeks gestation and older than 7 days

    10 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days.

    Premature Neonates less than 34 weeks gestation and 0 to 7 days

    10 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days.

    For the treatment of spontaneous bacterial peritonitis†.
    Intravenous dosage
    Adults

    600 mg IV every 12 hours as part of combination therapy for at least 5 to 7 days.

    For the treatment of peritoneal dialysis-related peritonitis†.
    Oral dosage
    Adults

    600 mg PO every 12 hours for 21 days.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for 14 to 21 days.

    Children 5 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for 14 to 21 days.

    Infants and Children 1 month to 4 years

    10 mg/kg/dose PO every 8 hours for 14 to 21 days.

    Intravenous dosage
    Adults

    600 mg IV every 12 hours for 21 days.

    Children and Adolescents 12 to 17 years

    600 mg IV every 12 hours for 14 to 21 days.

    Children 5 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) IV every 12 hours for 14 to 21 days.

    Infants and Children 1 month to 4 years

    10 mg/kg/dose IV every 8 hours for 14 to 21 days.

    For the treatment of peritoneal dialysis catheter-related infection†.
    Oral dosage
    Adults

    600 mg PO every 12 hours for at least 14 to 21 days.

    Children and Adolescents 12 to 17 years

    600 mg PO every 12 hours for at least 14 to 28 days.

    Children 5 to 11 years

    10 mg/kg/dose (Max: 600 mg/dose) PO every 12 hours for at least 14 to 28 days.

    Infants and Children 1 month to 4 years

    10 mg/kg/dose PO every 8 hours for at least 14 to 28 days.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    1,200 mg/day PO or IV.

    Geriatric

    1,200 mg/day PO or IV.

    Adolescents

    1,200 mg/day PO or IV.

    Children

    12 years: 1,200 mg/day PO or IV.
    1 to 11 years: 10 mg/kg/dose PO or IV every 8 hours (Max: 600 mg/dose).

    Infants

    10 mg/kg/dose PO or IV every 8 hours.

    Neonates

    10 mg/kg/dose PO or IV every 8 hours.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is recommended in mild to moderate hepatic insufficiency (Child-Pugh class A or B). Linezolid has not been studied in severe hepatic dysfunction, but dosage adjustments are probably not needed. Linezolid and its inactive metabolites are not metabolized via the liver.

    Renal Impairment

    Similar plasma concentrations are achieved regardless of the degree of renal impairment, no dosage adjustment is needed (manufacturer's recommendations). Follow normal dosage.
     
    Intermittent hemodialysis
    Linezolid and its metabolites are removed by hemodialysis. Roughly 30% of a linezolid dose is eliminated in a 3-hour hemodialysis session. Timing of dosage should allow for administration of a normally scheduled dose after a hemodialysis session (manufacturer's recommendation). For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.
     
    Peritoneal dialysis
    No dosage adjustment is necessary in adults and pediatric patients receiving the adult dosage. For pediatric patients younger than 12 years receiving 10 mg/kg/dose IV every 8 hours, reduce the dose to 10 mg/kg/dose IV every 12 hours.
     
    Continuous hemodialysis (CAVH, CVVH)
    Linezolid is significantly removed by CVVHD. The standard dose of at least 600 mg PO/IV twice daily is predicted to cover approximately 93% of organisms with an MIC up to 2 mg/L; higher doses may be required for organisms with an MIC up to 4 mg/L.

    ADMINISTRATION

    Oral Administration

    Administer without regard to food.[28599]
     
    When used for pulmonary extensively drug-resistant tuberculosis infection (XDR-TB) or treatment-intolerant or nonresponsive multidrug-resistant tuberculosis infection (MDR-TB) as part of a combination regimen with bedaquiline and pretomanid:
    Administer by directly observed therapy (DOT).
    Emphasize the need for compliance with the full course of therapy to patients.
    If the combination regimen is interrupted by a healthcare provider for safety reasons, missed doses can be made up at the end of treatment; do not make up doses of linezolid alone missed due to linezolid adverse reactions.
    If pretomanid or bedaquiline is discontinued, discontinue the entire combination regimen. If linezolid is permanently discontinued during the initial 4 consecutive weeks of treatment, discontinue the entire combination regimen. If linezolid is discontinued after the initial 4 weeks of consecutive treatment, continue pretomanid and bedaquiline therapy.[64561]

    Oral Liquid Formulations

    Before using, gently mix the constituted suspension well by turning the bottle gently upside down 3 or 5 times; do not shake the bottle before administration.
    Administer using a calibrated measuring device.[28599]
     
    Reconstitution of the oral suspension
    Review the manufacturer's reconstitution instructions for the particular product and package size; the amount of water to be used for reconstitution may vary between manufacturers.
    Prior to reconstitution, tap the bottle several times to loosen the powder.
    Add approximately half of the total amount of water needed and shake well. Add the remaining water and shake well.
    Storage: The prepared oral suspension may be kept at controlled room temperature, protected from light, for 21 days without significant loss of potency. Discard any unused suspension after 21 days.[28599]

    Injectable Administration

    Visually inspect parenteral products for leaks, particulate matter and discoloration prior to administration whenever solution and container permit. A yellow color may intensify over time but does not affect the potency of linezolid.

    Intravenous Administration

    Linezolid IV infusion is available in a concentration of 2 mg/mL as a pre-mixed sterile IV infusion in ready-to-use plastic infusion bags; no further dilution is required.
     
    Intermittent IV infusion
    Do not use the infusion bag in series connections. Do not introduce additives into the linezolid infusion solution.
    Linezolid is physically and chemically incompatible with several drugs during simultaneous Y-site administration. If the same intravenous line is used for the sequential infusion of several medications, the line should be flushed before and after the linezolid infusion.
    Compatible intravenous solutions for line flushing include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer's Injection.
    Keep the linezolid dose in the overwrap protected from light until ready to use.
    Infuse the ordered linezolid dosage IV over 30 to 120 minutes.

    STORAGE

    Zyvox:
    - Protect from light
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Phenylketonuria

    Linezolid is contraindicated in patients who have known hypersensitivity to linezolid or any of the other product components. Linezolid oral suspension contains phenylalanine, a component of aspartame. Before prescribing linezolid oral suspension to a patient with phenylketonuria, consider the combined daily amount of phenylalanine from all sources, including linezolid oral suspension. Other linezolid formulations do not contain phenylalanine.

    Bone marrow suppression

    Monitor complete blood counts weekly in patients who receive linezolid, particularly in those who receive linezolid for longer than 2 weeks, those with pre-existing bone marrow suppression, those receiving concomitant drugs that produce bone marrow suppression, or those with chronic infection who have received previous or concomitant antibacterial drug therapy. Consider discontinuing linezolid in patients who develop or have worsening myelosuppression. Myelosuppression has been reported in patients receiving linezolid. In cases where the outcome is known, when linezolid was discontinued, the affected hematologic parameters have risen toward pretreatment concentrations.[28599] In patients receiving linezolid as part of a combination regimen for tuberculosis, monitor complete blood counts at a minimum at baseline, at 2 weeks, and then monthly. Consider decreasing or interrupting linezolid dosing in patients who develop or have worsening myelosuppression during tuberculosis therapy.[64561]

    Hypertension, pheochromocytoma, thyrotoxicosis

    Unless patients are monitored for potential increases in blood pressure, do not administer linezolid to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, and/or patients taking directly and indirectly acting sympathomimetic agents, vasopressive agents, or dopaminergic agents. Unless clinically appropriate and patients are carefully observed for signs and/or symptoms of serotonin syndrome or neuroleptic malignant syndrome-like (NMS-like) reactions, do not administer linezolid to patients with carcinoid syndrome and/or patients taking serotonin re-uptake inhibitors, tricyclic antidepressants, bupropion, buspirone, serotonin 5-HT1 receptor agonists (triptans), or opioids.

    MAOI therapy

    Linezolid is a reversible, nonselective monoamine oxidase inhibitor (MAOI) and is contraindicated in patients receiving MAOI therapy or who have received an MAOI within the previous 14 days.

    C. difficile-associated diarrhea, diarrhea, pseudomembranous colitis

    Consider pseudomembranous colitis in patients presenting with diarrhea after antibacterial use. Careful medical history is necessary as pseudomembranous colitis has been reported to occur over 2 months after the administration of antibacterial agents. Almost all antibacterial agents, including linezolid, have been associated with pseudomembranous colitis or C. difficile-associated diarrhea (CDAD) which may range in severity from mild to life-threatening. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.[28599]

    Alcoholism, human immunodeficiency virus (HIV) infection, malnutrition, renal failure

    Monitor visual function in all patients taking linezolid for extended periods (3 months or more), in all patients reporting new visual symptoms regardless of length of linezolid therapy, and in all patients receiving linezolid as part of combination therapy for tuberculosis. Peripheral and optic neuropathies have been reported in patients treated with linezolid, primarily in those patients treated for longer than the maximum recommended duration of 28 days. In cases of optic neuropathy that progressed to loss of vision, patients were treated for extended periods beyond the maximum recommended duration.[28599] [64561] Persons living with human immunodeficiency virus (HIV) infection, as well as those with diabetes, alcoholism, malnutrition, chronic renal failure, and advanced age, may be predisposed to developing neuropathy. Concomitant pyridoxine is recommended in any patient receiving linezolid for tuberculosis and at risk for peripheral neuropathy.

    Diabetes mellitus

    While a causal relationship between linezolid and hypoglycemia has not been established, caution patients with diabetes mellitus of potential hypoglycemic reactions when treated with linezolid. Postmarketing cases of symptomatic hypoglycemia have been reported in patients with diabetes mellitus receiving insulin or oral hypoglycemic agents when treated with linezolid, a reversible, nonselective monoamine oxidase inhibitor (MAOI). Some MAOIs have been associated with hypoglycemic episodes in diabetic patients receiving insulin or hypoglycemic agents. Patients with diabetes mellitus may be predisposed to developing neuropathy. Concomitant pyridoxine is recommended in any patient receiving linezolid for tuberculosis and at risk for peripheral neuropathy.

    Seizure disorder, seizures

    Convulsions have been reported in patients when treated with linezolid. In some of these cases, a history of seizure disorder or risk factors for seizures was reported.

    Hyponatremia

    Monitor serum sodium concentrations regularly in patients at risk for hyponatremia and/or syndrome of inappropriate antidiuretic hormone secretion (SIADH), including the elderly and those taking diuretics during linezolid therapy. Postmarketing cases of hyponatremia and/or SIADH have been observed in patients treated with linezolid.

    Geriatric

    The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents (e.g., geriatric adults) of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions. Geriatric patients may be predisposed to developing neuropathy. Concomitant pyridoxine is recommended in any patient receiving linezolid for tuberculosis and at risk for peripheral neuropathy.

    Pregnancy

    Available data from published and postmarketing case reports with linezolid use during human pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered to pregnant animals during organogenesis, linezolid did not cause malformations at maternal exposures up to 6.5 times the clinical therapeutic exposure based on AUCs. However, embryofetal lethality was observed at 6.5 times the estimated human exposure.[28599]

    Breast-feeding

    Linezolid is present in breast milk. Based on available data, the daily dose of linezolid that the infant would receive from breast milk would be approximately 6% to 9% of the recommended therapeutic infant dose (10 mg/kg every 8 hours). There is no information on the effects of linezolid on the breast-fed infant; however, diarrhea and vomiting were the most common adverse reactions reported in clinical trials in infants receiving linezolid therapeutically. Advise breast-feeding women receiving linezolid to monitor the infant for diarrhea and vomiting. There is no information on the effects of linezolid on milk production. Consider the developmental and health benefits of breast-feeding along with the monther's clinical need for linezolid and any potential adverse effects on the breast-fed child from linezolid or the underlying maternal condition. Vancomycin, daptomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. Site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Alternative antimicrobials that previous American Academy of Pediatrics (AAP) recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.

    Infertility, reproductive risk

    Linezolid may be associated with reproductive risk. Based on findings in animal studies, linezolid may reversibly impair fertility in male patients. In male rats, linezolid contributed to infertility, possibly via epithelial cell hypertrophy in the epididymis, which affected proper maturation of sperm. In male dogs, decreased sperm motility was noted. No fertility changes occurred in female animals. Histologic pathological changes were not noted; decreased fertility was reversible on drug discontinuation.[28599]

    ADVERSE REACTIONS

    Severe

    C. difficile-associated diarrhea / Delayed / Incidence not known
    pancytopenia / Delayed / Incidence not known
    sideroblastic anemia / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    optic neuritis / Delayed / Incidence not known
    neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known
    serotonin syndrome / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    lactic acidosis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    vasculitis / Delayed / Incidence not known
    SIADH / Delayed / Incidence not known

    Moderate

    thrombocytopenia / Delayed / 0-12.9
    anemia / Delayed / 0-5.6
    eosinophilia / Delayed / 0.4-1.9
    candidiasis / Delayed / 0-1.8
    elevated hepatic enzymes / Delayed / 0.4-1.6
    hypoglycemia / Early / 0-1.0
    hypertension / Early / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    blurred vision / Early / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    bullous rash / Early / Incidence not known
    hyponatremia / Delayed / Incidence not known

    Mild

    diarrhea / Early / 8.0-11.0
    vomiting / Early / 2.0-9.4
    headache / Early / 0.9-8.8
    nausea / Early / 1.9-6.6
    dizziness / Early / 1.8-2.6
    abdominal pain / Early / 0.5-2.4
    rash / Early / 1.0-2.0
    dysgeusia / Early / 1.0-1.8
    pruritus / Rapid / 0.8-1.4
    tongue discoloration / Delayed / 0.3-1.3
    vertigo / Early / 0-1.2
    tooth discoloration / Delayed / Incidence not known
    vitamin B6 deficiency / Delayed / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Dihydrocodeine: (Contraindicated) Dihydrocodeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Acetaminophen; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Linezolid may enhance the hypertensive effect of isometheptene. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as isometheptene.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Acetaminophen; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Acetaminophen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Acetaminophen; Pentazocine: (Major) Avoid concomitant use of pentazocine in patients receiving linezolid due to the risk of serotonin syndrome. If coadministration or administration of pentazocine within 14 days of linezolid is warranted, carefully monitor patients, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use may also cause CNS excitation or hypertension.
    Acetaminophen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Acetohexamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Aclidinium; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Acrivastine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Albiglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Albuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Alfentanil: (Major) Avoid concomitant use of alfentanil in patients receiving linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If coadministration or administration of alfentanil within 14 days of linezolid is warranted, monitor patients for hypertension and serotonin syndrome. Ensure ready availability of vasodilators and beta-blockers for the treatment of hypertension, as needed. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Alogliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Alogliptin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Alogliptin; Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Amitriptyline: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Amoxapine: (Moderate) Amoxapine should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
    Amphetamines: (Contraindicated) Amphetamines should not be administered during or within 14 days after the use of linezolid. Linezolid possesses MAO-inhibiting activity and can prolong and intensify the cardiac stimulation and vasopressor effects of the amphetamines, potentially resulting in hypertensive crisis. Linezolid also has the potential to interact with serotonergic agents, such as amphetamines, which may increase the risk for serotonin syndrome. Serotonin syndrome is characterized by mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), and in rare instances, death. If serotonin syndrome occurs, discontinue serotonergic drugs and institute appropriate medical management.
    Arformoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Armodafinil: (Moderate) Use caution during coadministration of armodafinil with MAO inhibitors. Armodafinil has not been evaluated for drug interactions with monoamine oxidase inhibitors (MAOIs), including drugs with MAO inhibiting activity (e.g., linezolid). Other CNS stimulants may induce severe cardiovascular and cerebrovascular responses if administered in combination with drugs with MAO inhibitor activity.
    Articaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Contraindicated) Dihydrocodeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Aspirin, ASA; Carisoprodol; Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Aspirin, ASA; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Atenolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Atenolol; Chlorthalidone: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Atomoxetine: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Atomoxetine should not be taken with any MAOI, or within 2 weeks after discontinuing a MAOI and vice versa. Atomoxetine, a selective norepinephrine reuptake inhibitor, is contraindicated with the use of any MAOI due to the potential for serious reactions. Clinically, the potential for interaction between linezolid and atomoxetine has not been studied.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Atropine; Difenoxin: (Moderate) Linezolid may enhance the hypertensive effect of diphenoxylate. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate with MAOIs may, in theory, precipitate hypertensive crisis.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids. (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Bendroflumethiazide; Nadolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Benzhydrocodone; Acetaminophen: (Major) The use of benzhydrocodone is not recommended in patients who have received a monoamine oxidase inhibitor (MAOI) within 14 days. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of benzhydrocodone with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as benzhydrocodone.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Beta-adrenergic blockers: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Beta-agonists: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Betaxolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Bisoprolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Brimonidine: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Brinzolamide: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Brimonidine; Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers. (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
    Bromocriptine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Brompheniramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Brompheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Budesonide; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Bupivacaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Buprenorphine: (Major) Avoid concomitant use of buprenorphine in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Buprenorphine; Naloxone: (Major) Avoid concomitant use of buprenorphine in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Bupropion: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid.
    Bupropion; Naltrexone: (Contraindicated) Due to an increased risk of hypertensive reactions, treatment initiation with bupropion is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than bupropion (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving bupropion and requiring urgent treatment with linezolid, bupropion should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for hypertensive reactions for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Bupropion may be re-initiated 24 hours after the last dose of linezolid.
    Buspirone: (Contraindicated) Due to an increased risk of serotonin syndrome, treatment initiation with buspirone is contraindicated in patients currently receiving linezolid, an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. If urgent psychiatric treatment is required, interventions other than buspirone (e.g., alternative medication, hospitalization) should be considered. In patients receiving buspirone and requiring urgent treatment with linezolid, buspirone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Buspirone may be re-initiated 24 hours after the last dose of linezolid.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Butorphanol: (Major) Avoid concomitant use of butorphanol with linezolid due to the risk of serotonin syndrome. If concomitant use is warranted, carefully monitor the patient, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of any MAOI.
    Caffeine; Sodium Benzoate: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Canagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Capsaicin; Metaxalone: (Moderate) Concomitant use of linezolid and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
    Carbamazepine: (Major) Carbamazepine is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if carbamazepine could cause decreases in linezolid exposure if coadministered. Additionally, linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor; therefore, linezolid has the potential for interaction with carbamazepine. Carbamazepine, a dibenazepine-related drug, should not be coadministered with MAO inhibitors. Hypertensive crises, seizures, coma, or circulatory collapse may occur in patients receiving this combination. MAOIs should be discontinued for a minimum of 14 days or longer if the clinical situation permits, before administering carbamazepine.
    Carbetapentane; Chlorpheniramine: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine. (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbetapentane; Pyrilamine: (Minor) Carbetapentane should be avoided in patients receiving MAOIs, and should not be used within 14 days of discontinuation of an MAOI. Carbetapentane has similar pharmacologic properties to dextromethorphan, and can block neuronal uptake of serotonin. Excessive concentrations of serotonin in the CNS may occur if carbetapentane is combined with MAOIs, including drugs with MAO-inhibiting activity. A serotonin syndrome, consisting of nausea, hypotension, excitation, hyperpyrexia, and coma is possible.
    Carbidopa; Levodopa: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Carbidopa; Levodopa; Entacapone: (Major) Avoid the concomitant use of COMT inhibitors in combination with linezoid, which has non-selective monoamine oxidase (MAO) inhibitor activity. Typically, at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Consider an alternative to linezolid if possible. Monoamine oxidase and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the coadministration of a COMT inhibitor with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity. (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carbinoxamine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Carbinoxamine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Carteolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Carvedilol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Celecoxib; Tramadol: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Cetirizine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlordiazepoxide; Amitriptyline: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Chlorpheniramine; Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Chlorpheniramine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Contraindicated) Dihydrocodeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Contraindicated) Dihydrocodeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpheniramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Chlorpheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Chlorpropamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Citalopram: (Contraindicated) According to the manufacturer of citalopram, treatment initiation with citalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than citalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving citalopram and requiring urgent treatment with linezolid, citalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Citalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with citalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Clomipramine: (Contraindicated) According to the manufacturer of clomipramine, treatment initiation with clomipramine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than clomipramine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving clomipramine and requiring urgent treatment with linezolid, clomipramine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Clomipramine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with clomipramine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Cocaine: (Major) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of an indirect-acting sympathomimetic, like cocaine, to patients receiving a MAOI may invoke a hypertensive reaction. In general, traditional MAO inhibitors should be discontinued for 10 days prior to elective surgery with general anesthetics or spinal anesthesia if possible.
    Codeine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Guaifenesin: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Codeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Codeine; Phenylephrine; Promethazine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Codeine; Promethazine: (Contraindicated) Codeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    COMT inhibitors: (Major) Avoid the concomitant use of COMT inhibitors in combination with linezoid, which has non-selective monoamine oxidase (MAO) inhibitor activity. Typically, at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Consider an alternative to linezolid if possible. Monoamine oxidase and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the coadministration of a COMT inhibitor with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity.
    Cyclobenzaprine: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Hypertensive crises, severe convulsive seizures, coma, or circulatory collapse may occur in patients receiving cyclobenzaprine concomitantly.
    Dapagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Dapagliflozin; Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Desipramine: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Desloratadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Desogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Desvenlafaxine: (Contraindicated) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as desvenlafaxine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving desvenlafaxine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, desvenlafaxine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with desvenlafaxine may be resumed 24 hours after the last dose of linezolid.
    Dexbrompheniramine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dextromethorphan; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine. (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dextromethorphan; Quinidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Dienogest; Estradiol valerate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Diethylpropion: (Major) Linezolid can prolong and intensify the cardiac stimulation and vasopressor effects of diethylpropion. Diethylpropion should not be administered during, or within 14 days following the use of MAOIs, or drugs with MAO-inhibiting activity.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Contraindicated) Dihydrocodeine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Dihydroergotamine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Diphenhydramine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Diphenoxylate; Atropine: (Moderate) Linezolid may enhance the hypertensive effect of diphenoxylate. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate with MAOIs may, in theory, precipitate hypertensive crisis.
    Dobutamine: (Major) Linezolid may enhance the hypertensive effect of dobutamine. Initial doses of dobutamine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as dobutamine.
    Dolasetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Dopamine: (Major) Linezolid may enhance the hypertensive effect of dopamine. Initial doses of dopamine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as dopamine.
    Dorzolamide; Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Doxapram: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor; therefore, linezolid has the potential for interaction with doxapram. Hypertension and other adverse CNS or cardiovascular effects can occur. At least 2 weeks should elapse between discontinuation of one agent and initiation of therapy with the other.
    Doxepin: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than a TCA (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with doxepin or other TCAs can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Drospirenone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estetrol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Droxidopa: (Major) Avoid concurrent use of droxidopa and linezolid, a non-selective MAOI, as there is a potential for increased blood pressure when taken together.
    Dulaglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Duloxetine: (Contraindicated) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as duloxetine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving duloxetine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, duloxetine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with duloxetine may be resumed 24 hours after the last dose of linezolid.
    Elagolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Empagliflozin; Linagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Empagliflozin; Linagliptin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Empagliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Entacapone: (Major) Avoid the concomitant use of COMT inhibitors in combination with linezoid, which has non-selective monoamine oxidase (MAO) inhibitor activity. Typically, at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Consider an alternative to linezolid if possible. Monoamine oxidase and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the coadministration of a COMT inhibitor with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity.
    Ephedrine: (Moderate) Linezolid may enhance the hypertensive effect of ephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as ephedrine.
    Ephedrine; Guaifenesin: (Moderate) Linezolid may enhance the hypertensive effect of ephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as ephedrine.
    Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Ergoloid Mesylates: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergonovine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergot alkaloids: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergotamine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ergotamine; Caffeine: (Moderate) Caffeine use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs. (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Ertugliflozin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Ertugliflozin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Escitalopram: (Contraindicated) According to the manufacturer of escitalopram, treatment initiation with escitalopram is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than escitalopram (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving escitalopram and requiring urgent treatment with linezolid, escitalopram should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Escitalopram may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with escitalopram can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Esmolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethanol: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Some alcohol-based products also contain tyramine including some beers; wines; sherry; hard liquor; or liqueurs and should be avoided.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Exenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Fenfluramine: (Contraindicated) Coadministration of fenfluramine with monoamine oxidase inhibitors (MAOIs), such as linezolid, or within 14 days after discontinuation of treatment with linezolid is contraindicated due to the risk of serotonin syndrome.
    Fentanyl: (Major) Avoid concomitant use of fentanyl in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Fexofenadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Fluoxetine: (Contraindicated) According to the manufacturer of fluoxetine, treatment initiation with fluoxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluoxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluoxetine and requiring urgent treatment with linezolid, fluoxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluoxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluoxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Fluticasone; Salmeterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fluvoxamine: (Contraindicated) According to the manufacturer of fluvoxamine, treatment initiation with fluvoxamine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluvoxamine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluvoxamine and requiring urgent treatment with linezolid, fluvoxamine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluvoxamine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluvoxamine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Food: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. Foods containing tyramine should be avoided.
    Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Formoterol; Mometasone: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Fosphenytoin: (Minor) Coadministration of linezolid and fosphenytoin, which is metabolized by the CYP2C9 isoenzyme, does not substantially alter the pharmacokinetics of phenytoin. No change in the fosphenytoin dosage regimen is necessary. Also, phenytoin is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if fosphenytoin could cause decreases in linezolid exposure if coadministered.
    Ginseng, Panax ginseng: (Major) There have been two reports in the literature describing a possible, but not definitive, interaction between ginseng, panax ginseng and phenelzine; it is not clear if other MAOIs or drugs that possess MAOI-like activity, such as linezolid, would interact, but caution is warranted. In one case, headache and tremulousness were reported in a 64-year old when ginseng was added to phenelzine. A second patient suffered from irritability, headache, and vague visual hallucinations during combined use of ginseng and phenelzine. Some of these effects have been reported with the use of phenelzine alone.
    Glimepiride: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glimepiride; Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glipizide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glipizide; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glyburide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glyburide; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Glycopyrrolate; Formoterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Granisetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Green Tea: (Moderate) Green tea use should be minimized or avoided during and for 1 to 2 weeks after discontinuation of linezolid. Green tea catechins inhibit Catechol-O-methyltransferase (COMT) in animals. Monoamine oxidase (MAO) and COMT are the two major enzymes involved in the metabolism of catecholamines. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). In addition, some green tea products contain caffeine; caffeine interacts with MAOIs. Dangerous cardiac arrhythmias or severe hypertension can occur because of the potentiation of caffeine's sympathomimetic effects by MAOIs.
    Guaifenesin; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Guaifenesin; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Guaifenesin; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Guanabenz: (Major) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Guanabenz withdrawal can result in an increase in serum catecholamine levels. Thus, drugs that alter the metabolism or uptake of catecholamines, such as monoamine oxidase inhibitors (MAOIs), should be used cautiously in patients who are undergoing guanabenz withdrawal.
    Homatropine; Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Hydrocodone: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of hydrocodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Hydromorphone: (Major) Avoid concomitant use of hydromorphone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Ibuprofen; Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Ibuprofen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Imipramine: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Incretin Mimetics: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Indacaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Insulin Degludec; Liraglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Insulin Glargine; Lixisenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Insulins: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Iobenguane I 131: (Major) Discontinue linezolid for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart linezolid until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as linezolid, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy.
    Iohexol: (Major) Discontinue linezolid at least 48 hours before myelography with iohexol and do not resume for at least 24 hours post procedure due to increased seizure risk. In non-elective procedures in patients on these drugs, consider prophylactic use of anticonvulsants.
    Iopamidol: (Major) Discontinue linezolid at least 48 hours before myelography with iopamidol and do not resume for at least 24 hours post procedure due to increased seizure risk. In non-elective procedures in patients on these drugs, consider prophylactic use of anticonvulsants.
    Ipratropium; Albuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Isocarboxazid: (Contraindicated) Concomitant use of linezolid with monoamine oxidase inhibitors (MAOIs) or use of linezolid within 2 weeks of taking an MAOI is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Isoniazid, INH: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI. (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Isoniazid, INH; Rifampin: (Major) In theory, concurrent use of isoniazid, INH with other drugs that possess MAO-inhibiting activity, such as linezolid, may result in hypertensive crises, fever, delirium, circulatory collapse, seizures, coma, or death. Similar severe adverse events have occurred after combining other MAOIs. The manufacturer of linezolid contraindicates use of linezolid with any monoamine oxidase inhibitor (MAOI) or within two weeks of taking an MAOI. Monoamine oxidase (MAO) is an enzyme system which contributes to the degradation of neurotransmitters such as dopamine, serotonin, and norepinephrine. Isoniazid has weak MAOI properties and is chemically-related to iproniazid, a drug that was known to possess MAO-inhibiting activity. Linezolid is an antibiotic that is also a non-selective MAOI. (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Isoproterenol: (Major) Linezolid may enhance the hypertensive effect of isoproterenol. Initial doses of isoproterenol should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as isoproterenol.
    Labetalol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and linezolid. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
    Leuprolide; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levalbuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Levobetaxolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Levobunolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Levodopa: (Major) Concomitant use of levodopa (including carbidopa; levodopa and carbidopa; levodopa; entacapone) and drugs with monoamine oxidase inhibitor (MAOI) activity, such as linezolid, can result in hypertensive crisis. Simultaneous use of these agents should be avoided if possible.
    Levomilnacipran: (Contraindicated) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as levomilnacipran is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving levomilnacipran may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, levomilnacipran should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with levomilnacipran may be resumed 24 hours after the last dose of linezolid.
    Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levonorgestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Levorphanol: (Major) Avoid concomitant use of levorphanol with linezolid due to the risk of serotonin syndrome. If concomitant use is warranted, carefully monitor the patient, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Lidocaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Linagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Linagliptin; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Liraglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Lithium: (Major) There is an increased risk of serotonin syndrome during concurrent use of drugs with central serotonergic properties such as lithium and linezolid. Signs and symptoms of serotonin syndrome include autonomic instability (e.g., labile blood pressure, tachycardia, diaphoresis, dizziness, hyperthermia), mental status changes (e.g., delirium, confusion, coma), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), gastrointestinal effects (e.g., nausea, vomiting, diarrhea), seizures, and in rare cases, death. If concurrent use is necessary, monitor for the emergence of serotonin syndrome and inform patients of the increased risk. If serotonin syndrome is suspected, serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Lixisenatide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Loratadine; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Lorcaserin: (Major) Based on the mechanism of action of lorcaserin and the theoretical potential for serotonin syndrome, use with extreme caution in combination with other drugs that may affect the serotonergic neurotransmitter systems, including linezolid, an antibiotic that is also a reversible, non-selective MAO inhibitor. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent clinical use of linezolid and medications that enhance central serotonergic activity.
    Maprotiline: (Moderate) Maprotiline should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Maprotiline is a selective norepinephrine reuptake inhibitor. Therefore, the potential for serotonin syndrome during coadministration of maprotiline and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
    Meglitinides: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Meperidine: (Contraindicated) Meperidine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or precipitation of other unpredictable, severe, and occasionally fatal reactions, possibly related to preexisting hyperphenylalaninemia.
    Meperidine; Promethazine: (Contraindicated) Meperidine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or precipitation of other unpredictable, severe, and occasionally fatal reactions, possibly related to preexisting hyperphenylalaninemia.
    Mestranol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Metaproterenol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Metaxalone: (Moderate) Concomitant use of linezolid and metaxalone may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
    Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Repaglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Metformin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Methadone: (Major) Avoid concomitant use of methadone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methyldopa: (Contraindicated) Methyldopa is contraindicated for use with monoamine oxidase inhibitors (MAOIs). Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Administration of MAOIs with methyldopa has resulted in headaches, severe hypertension, and hallucinations, although data describing the interaction between MAOIs and methyldopa are limited.
    Methylene Blue: (Major) Concurrent use of methylene blue and medications with serotonergic effects, such as linezolid, should be avoided if possible. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin in the brain (MAO-A) and linezolid is an antibiotic with reversible, non-selective MAO inhibitor activity. Since MAO type A deaminates serotonin, administration of linezolid concurrently with another agent with MAO-A inhibiting activity can potentially increase serotonin. Cases of serotonin syndrome have been reported, primarily following administration of standard infusions of methylene blue (1 to 8 mg/kg) as a visualizing agent in parathyroid surgery, in patients receiving selective serotonergic agents. It is not known if patients receiving intravenous methylene blue with linezolid are at a comparable risk. Serotonin syndrome is characterized by rapid development of various symptoms such as hyperthermia, hypertension, myoclonus, rigidity, hyperhidrosis, incoordination, diarrhea, mental status changes (e.g., confusion, delirium, or coma), and in rare cases, death.
    Methylergonovine: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Methylphenidate Derivatives: (Major) Psychostimulants, such as methylphenidate derivatives, exhibit sympathomimetic actions and should be avoided with other drugs, such as linezolid, that enhance the pressor response of sympathomimetic agents. A clinically significant rise in systolic blood pressure is possible. In addition, serotonin syndrome has been reported during the concurrent use of linezolid, a non-selective monoamine oxidase inhibitor (MAOI), and medications that enhance central serotonergic activity. Monoamine oxidase (MAO) is the enzyme responsible for the degradation of norepinephrine, dopamine, and serotonin. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Patients receiving this combination should be monitored for the emergence of serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical management should be implemented.
    Methysergide: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Metoclopramide: (Major) Because metoclopramide causes release of catecholamines in patients with essential hypertension, it should be administered cautiously to patients receiving MAOIs or drugs that possess MAOI-like activity, such as linezolid.
    Metoprolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Midodrine: (Major) Avoid the concomitant use of linezolid with midodrine. Linezolid may enhance the hypertensive effect of midodrine. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as midodrine.
    Milnacipran: (Contraindicated) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as milnacipran is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving milnacipran may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, milnacipran should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 5 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with milnacipran may be resumed 24 hours after the last dose of linezolid.
    Mirtazapine: (Contraindicated) Concurrent use of linezolid and mirtazapine is contraindicated due to an increased risk of serotonin syndrome. Mirtazapine is a serotonergic antidepressant and linezolid is a nonselective inhibitor of monoamine oxidase which increases central serotonin levels. If urgent psychiatric treatment is required, interventions other than mirtazapine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving mirtazapine and requiring urgent treatment with linezolid, mirtazapine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Mirtazapine may be resumed 24 hours after the last dose of linezolid.
    Modafinil: (Moderate) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of modafinil to patients receiving linezolid may invoke a hypertensive reaction. Such drugs should be avoided during and for up to 2 weeks following the discontinuation of linezolid.
    Monoamine oxidase inhibitors: (Contraindicated) Concomitant use of linezolid with monoamine oxidase inhibitors (MAOIs) or use of linezolid within 2 weeks of taking an MAOI is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Morphine: (Contraindicated) Morphine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity.
    Morphine; Naltrexone: (Contraindicated) Morphine use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity.
    Nadolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Nalbuphine: (Major) Avoid concomitant use of nalbuphine in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Naproxen; Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Nateglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Nebivolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Nebivolol; Valsartan: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Nefazodone: (Major) Linezolid should generally not be administered to patients taking serotonergic agents, such as nefazodone, due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of nefazodone; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Netupitant, Fosnetupitant; Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Norepinephrine: (Major) Linezolid may enhance the hypertensive effect of norepinephrine. Initial doses of norepinephrine should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as norepinephrine.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestimate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Nortriptyline: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Olanzapine; Fluoxetine: (Contraindicated) According to the manufacturer of fluoxetine, treatment initiation with fluoxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than fluoxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving fluoxetine and requiring urgent treatment with linezolid, fluoxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for five weeks or until 24 hours after the last dose of linezolid, whichever comes first. Fluoxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with fluoxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Oliceridine: (Major) Avoid concomitant use of oliceridine with linezolid due to the risk of serotonin syndrome. If concomitant use is warranted, carefully monitor the patient, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Olodaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Ondansetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering ondansetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue ondansetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Opicapone: (Major) Avoid the concomitant use of COMT inhibitors in combination with linezoid, which has non-selective monoamine oxidase (MAO) inhibitor activity. Typically, at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Consider an alternative to linezolid if possible. Monoamine oxidase and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the coadministration of a COMT inhibitor with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Oxycodone: (Major) Avoid concomitant use of oxycodone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Oxymorphone: (Major) Avoid concomitant use of oxymorphone in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Ozanimod: (Contraindicated) Coadministration of ozanimod with monoamine oxidase (MAO) inhibitors, like linezolid, is contraindicated. Allow at least 14 days between discontinuation of ozanimod and initiation of treatment with linezolid. Metabolites of ozanimod may inhibit MAO. The potential for a clinical interaction with MAO inhibitors has not been studied; however, the increased risk of nonselective MAO inhibition may lead to a hypertensive crisis.
    Palonosetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering palonosetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue palonosetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Paroxetine: (Contraindicated) According to the manufacturer of paroxetine, treatment initiation with paroxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than paroxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving paroxetine and requiring urgent treatment with linezolid, paroxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Paroxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with paroxetine can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Penbutolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Pentazocine: (Major) Avoid concomitant use of pentazocine in patients receiving linezolid due to the risk of serotonin syndrome. If coadministration or administration of pentazocine within 14 days of linezolid is warranted, carefully monitor patients, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use may also cause CNS excitation or hypertension.
    Pentazocine; Naloxone: (Major) Avoid concomitant use of pentazocine in patients receiving linezolid due to the risk of serotonin syndrome. If coadministration or administration of pentazocine within 14 days of linezolid is warranted, carefully monitor patients, especially during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use may also cause CNS excitation or hypertension.
    Pergolide: (Moderate) Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity; therefore, caution is warranted with concomitant use of other agents with serotonergic activity, including ergot alkaloids.
    Perphenazine; Amitriptyline: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Phendimetrazine: (Moderate) Linezolid may enhance the hypertensive effect of phendimetrazine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phendimetrazine.
    Phenelzine: (Contraindicated) Concomitant use of linezolid with monoamine oxidase inhibitors (MAOIs) or use of linezolid within 2 weeks of taking an MAOI is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Phenobarbital: (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) Phenobarbital is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenobarbital could cause decreases in linezolid exposure if these drugs are coadministered.
    Phentermine: (Major) Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction. Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome.
    Phentermine; Topiramate: (Major) Phentermine should not be administered during or within 14 days following the use of linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Drugs that possess MAO-inhibiting activity, such as linezolid, can prolong and intensify the cardiac stimulation and vasopressor effects of phentermine which may invoke a hypertensive reaction. Additonally, phentermine has a weak ability to dose-dependently raise serotonin levels. Linezolid has the potential for interaction with serotonergic agents, which may increase the risk for serotonin syndrome. If coadministration is necessary, closely monitor for increased blood pressure and signs of serotonin syndrome.
    Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Phenytoin: (Minor) Coadministration of linezolid and phenytoin, which is metabolized by the CYP2C9 isoenzyme, does not substantially alter the pharmacokinetics of phenytoin. No changes in the phenytoin dosage regimen is necessary. Also, phenytoin is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if phenytoin could cause decreases in linezolid exposure if coadministered.
    Pindolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Pioglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Pioglitazone; Glimepiride: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Pioglitazone; Metformin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Pirbuterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Pramlintide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Prilocaine; Epinephrine: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine.
    Primidone: (Minor) Primidone is metabolized to phenobarbital, which is a strong inducer of the CYP450 enzyme system. The AUC and Cmax of linezolid were decreased when coadministered with another strong CYP450 inducer, rifampin. It is unknown if primidone could cause decreases in linezolid exposure if these drugs are coadministered.
    Procarbazine: (Contraindicated) Concurrent use of linezolid with procarbazine or use of linezolid within 2 weeks of taking procarbazine is contraindicated due to the risk of severe hypertensive crisis. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Linezolid should not be used concurrently with other drugs that possess MAOI-like activity, such as procarbazine.
    Promethazine; Dextromethorphan: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering linezolid with dextromethorphan. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor and has potential to interact with serotonergic agents. Dextromethorphan has serotonergic activity. However, the potential for interaction has been studied. Subjects were administered dextromethorphan (two 20-mg doses given 4 hours apart) with or without linezolid. No serotonin syndrome effects (confusion, delirium, restlessness, tremors, blushing, diaphoresis, hyperpyrexia) have been observed in normal subjects receiving linezolid and dextromethorphan.
    Promethazine; Phenylephrine: (Major) Linezolid may enhance the hypertensive effect of phenylephrine. Initial doses of phenylephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as phenylephrine.
    Propranolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Protriptyline: (Contraindicated) Concurrent use of drugs with MAO-inhibiting activity, such as linezolid, with tricyclic antidepressants (TCAs) can cause hyperpyrexia, hypertension, or seizures. The combination should be avoided whenever possible. In general, linezolid should generally not be administered to patients taking serotonergic agents due to the potential for serious CNS reactions, such as serotonin syndrome. Serotonin syndrome has been reported when linezolid has been administerd with certain serotonergic agents. In theory, serotonin syndome could occur with the concomitant use of TCAs; however, the FDA states that it is unclear if concomitant use of linezolid and agents with lesser degrees of serotonergic activity would pose a comparable risk. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Pseudoephedrine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Pseudoephedrine; Triprolidine: (Moderate) Linezolid may enhance the hypertensive effect of pseudoephedrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as pseudoephedrine.
    Racepinephrine: (Moderate) Linezolid may enhance the hypertensive effect of racepinephrine. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as racepinephrine.
    Rasagiline: (Contraindicated) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Concurrent use of linezolid with medications that inhibit either monoamine oxidase A or B or use of linezolid within 2 weeks of taking monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of severe hypertensive crisis and possibly serotonin syndrome. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including agents like MAOIs, which can potentiate serotonin.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Remifentanil: (Major) Avoid concomitant use of remifentanil in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Repaglinide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Reserpine: (Moderate) Concomitant use of linezolid and reserpine can cause hypertension and increased excitation. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Reserpine depletes intracellular catecholamines by initially causing their release from bound stores, so the acute administration of reserpine to patients currently taking an MAOI can lead to hypertensive crisis.
    Rifampin: (Minor) In a study of healthy volunteers (n=16), coadministration of rifampin (600 mg daily administered for 8 days) with oral linezolid (600 mg twice daily administered for 5 days) resulted in a 21% decrease in linezolid Cmax (90% CI, 15-27%) and a 32% decrease in linezolid AUC (90% CI, 27-37%). The clinical significance of this interaction is unknown and the mechanism is not fully understood, but it may be related to the induction of hepatic enzymes. Caution may be warranted if linezolid and rifampin are coadministered.
    Ritodrine: (Major) Linezolid is an antibiotic which is a reversible, non-selective inhibitor of MAO. Administration of ritodrine to patients receiving linezolid may invoke a hypertensive reaction. Such drugs should be avoided during and for up to 2 weeks following the discontinuation of linezolid.
    Rosiglitazone: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Safinamide: (Contraindicated) Concurrent use of linezolid with safinamide, a monoamine oxidase inhibitor type B, or use of linezolid within 2 weeks of taking safinamide is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including monoamine oxidase inhibitors (MAOIs), which can potentiate central serotonin levels.
    Salmeterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Saxagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Segesterone Acetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Selegiline: (Contraindicated) Concurrent use of linezolid with selegiline, a monoamine oxidase inhibitor type B (MAO-B inhibitor), or use of linezolid within 2 weeks of taking selegiline is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Semaglutide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Serotonin-Receptor Agonists: (Major) Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO and should not be administered with serotonin-receptor agonists. The monoamine oxidase type A enzyme metabolizes serotonin. Non-selective MAO inhibitors increase the plasma concentrations of these drugs and some of their active metabolites, thus increasing levels of serotonin. This interaction could lead to serotonin syndrome. The manufacturers of serotonin agonists contraindicate the administration of their drugs to patients receiving non-selective MAO inhibitors like linezolid or within 2 weeks of discontinuation of a MAO inhibitor.
    Sertraline: (Contraindicated) According to the manufacturer of sertraline, treatment initiation with sertraline is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than sertraline (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving sertraline and requiring urgent treatment with linezolid, sertraline should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Sertraline may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with sertraline can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. Serotonin syndrome has been reported in patients receiving either citalopram, escitalopram, fluoxetine, or paroxetine in combination with linezolid.
    Sibutramine: (Major) Linezolid possesses weak non-selective MAO-inhibiting activity and concurrent use of any of these agents with sibutramine should be avoided if possible. The concomitant use of sibutramine with MAOIs is contraindicated. Sibutramine is a serotonin reuptake inhibitor. Since serotonin is deaminated by monoamine oxidase-A, concurrent administration of sibutramine with drugs that inhibit this enzyme such as MAOIs can lead to serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. There should be at least a 2-week interval between discontinuation of MAOI therapy and initiation of sibutramine therapy. Similarly, there should be at least a 2-week interval after stopping sibutramine therapy and the start of MAOI therapy.
    Simvastatin; Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Sitagliptin: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    St. John's Wort, Hypericum perforatum: (Contraindicated) Linezolid should generally not be administered to patients taking serotonergic agents, such as St. John's wort, Hypericum perforatum, due to the potential for serious CNS reactions, such as serotonin syndrome. The FDA recommends that if linezolid must be administered to patients already taking serotonergic agents due to life-threatening conditions, the serotonergic agent should be discontinued immediately and the patient should be monitored for emergence of symptoms of CNS toxicity for two weeks, or until 24 hours after the last dose of linezolid, whichever comes first. For non-emergent situations, most serotonergic drugs should be stopped at least 2 weeks prior to instituting linezolid therapy. Treatment with serotonergic agents may resume 24 hours after the discontinuation of linezolid. Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Sufentanil: (Major) Avoid concomitant use of sufentanil in patients receiving linezolid or within 14 days of stopping treatment with linezolid due to the risk of serotonin syndrome or opioid toxicity, including respiratory depression.
    Sulfonylureas: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tapentadol: (Contraindicated) Tapentadol use in patients taking linezolid or within 14 days of stopping such treatment is contraindicated due to the risk of serotonin syndrome or opioid toxicity. If urgent use of an opioid is necessary, use test doses and frequent titration of small doses of another opioid to treat pain while closely monitoring blood pressure and signs and symptoms of CNS and respiratory depression.
    Terbutaline: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Tetrahydrozoline: (Moderate) Linezolid may enhance the hypertensive effect of tetrahydrozoline. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as tetrahydrozoline.
    Thiazolidinediones: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Timolol: (Moderate) Linezolid is an antibiotic that is also a reversible, non-selective MAO inhibitor. Bradycardia may be worsened when MAO-inhibitors are co-administered to patients receiving beta-blockers. Use linezolid cautiously in patients receiving beta-blockers.
    Tiotropium; Olodaterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Tolazamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tolbutamide: (Moderate) Hypoglycemia, including symptomatic episodes, has been noted in post-marketing reports with linezolid in patients with diabetes mellitus receiving therapy with antidiabetic agents, such as insulin and oral hypoglycemic agents. Diabetic patients should be monitored for potential hypoglycemic reactions while on linezolid. If hypoglycemia occurs, discontinue or decrease the dose of the antidiabetic agent or discontinue the linezolid therapy. Linezolid is a reversible, nonselective MAO inhibitor and other MAO inhibitors have been associated with hypoglycemic episodes in diabetic patients receiving insulin or oral hypoglycemic agents.
    Tolcapone: (Major) Avoid the concomitant use of COMT inhibitors in combination with linezoid, which has non-selective monoamine oxidase (MAO) inhibitor activity. Typically, at least 14 days should elapse between the discontinuation of a non-selective MAOI and the use of a COMT inhibitor to avoid potential interactions. Consider an alternative to linezolid if possible. Monoamine oxidase and catechol-O-methyltransferase (COMT) are the two major enzymes involved in the metabolism of catecholamines. It is theoretically possible that the coadministration of a COMT inhibitor with linezolid would result in inhibition of normal catecholamine metabolism and possible toxicity.
    Tramadol: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Tramadol; Acetaminophen: (Contraindicated) Tramadol use is contraindicated in patients who are receiving or who have received monoamine oxidase inhibitors (MAOIs) within the previous 14 days. Linezolid is a reversible, non-selective inhibitor of MAO. Concomitant use of tramadol with other serotonergic drugs such as MAOIs may result in serious adverse effects including serotonin syndrome or seizures. MAOIs may cause additive CNS depression, respiratory depression, drowsiness, dizziness, or hypotension when used with opiate agonists such as tramadol.
    Tranylcypromine: (Contraindicated) Concomitant use of linezolid with monoamine oxidase inhibitors (MAOIs) or use of linezolid within 2 weeks of taking an MAOI is contraindicated due to the risk of increased blood pressure, including hypertensive crisis. Linezolid is an antibiotic that is also a potent inhibitor of monoamine oxidase. Serotonin syndrome has also been reported when linezolid is given with serotonergic agents, including MAOIs, which can potentiate central serotonin levels.
    Trazodone: (Contraindicated) Concurrent use of linezolid and trazodone is contraindicated due to an increased risk of serotonin syndrome. Trazodone is a serotonergic antidepressant and linezolid is a nonselective inhibitor of monoamine oxidase which increases central serotonin levels. If urgent psychiatric treatment is required, interventions other than trazodone (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving trazodone and requiring urgent treatment with linezolid, trazodone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid, whichever comes first. Trazodone may be resumed 24 hours after the last dose of linezolid.
    Trimipramine: (Contraindicated) Treatment with tricyclic antidepressants (TCAs) is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than tricyclic antidepressant therapy (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving a TCA and requiring urgent treatment with linezolid, the TCA should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. The TCA may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with a TCA can lead to serious reactions including serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Tryptophan, 5-Hydroxytryptophan: (Major) Avoid use of dietary supplements containing tryptophan in patients taking linezolid. Coadministration may increase the risk for serotonin syndrome. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of monoamine oxidase (MAOI). Tryptophan is a serotonin precursor. Serious CNS reactions, such as serotonin syndrome, have been reported during the concurrent use of linezolid and psychiatric medications that enhance central serotonergic activity.
    Umeclidinium; Vilanterol: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Valerian, Valeriana officinalis: (Major) Any substances that act on the CNS may theoretically interact with valerian, Valeriana officinalis. The valerian derivative, dihydrovaltrate, binds at barbiturate binding sites; valerenic acid has been shown to inhibit enzyme-induced breakdown of GABA in the brain; the non-volatile monoterpenes (valepotriates) have sedative activity. Patients taking MAOIs or drugs that possess MAOI-like activity, such as linezolid, should discuss the use of herbal supplements with their health care professional prior to consuming valerian; combinations should be approached with caution in the absence of clinical data.
    Venlafaxine: (Contraindicated) The use of linezolid with serotonin norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine is contraindicated due to the potential for serotonin syndrome. Linezolid is an antibiotic that also possesses weak non-selective MAO-inhibiting activity which could have additive effects with SNRIs on central serotonin activity. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. In a patient who requires urgent treatment of a psychiatric condition, interventions other than an SNRI, including hospitalization, should be considered. In some cases, a patient already receiving venlafaxine may require urgent treatment with linezolid. If acceptable alternatives to linezolid are not available and the potential benefits of linezolid are determined to outweigh the risks of serotonin syndrome in an individual patient, venlafaxine should be stopped promptly, and linezolid can be administered. The patient should be monitored for symptoms of serotonin syndrome for 7 days or until 24 hours after the last dose of linezolid, whichever comes first. Therapy with venlafaxine may be resumed 24 hours after the last dose of linezolid.
    Vilazodone: (Contraindicated) According to the manufacturer of vilazodone, treatment initiation with vilazodone is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than vilazodone (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving vilazodone and requiring urgent treatment with linezolid, vilazodone should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for two weeks or until 24 hours after the last dose of linezolid, whichever comes first. Vilazodone may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with vilazodone can lead to serotonin syndrome. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
    Vortioxetine: (Contraindicated) Treatment initiation with vortioxetine is contraindicated in patients currently receiving linezolid due to an increased risk of serotonin syndrome. If urgent psychiatric treatment is required, interventions other than vortioxetine (e.g., alternative medication, hospitalization) should be considered. Conversely, in patients receiving vortioxetine and requiring urgent treatment with linezolid, vortioxetine should be discontinued immediately and linezolid therapy initiated only if acceptable alternatives are not available and the potential benefits of linezolid outweigh the risks. The patient should be monitored for serotonin syndrome for 21 days or until 24 hours after the last dose of linezolid, whichever comes first. Vortioxetine may be re-initiated 24 hours after the last dose of linezolid. Linezolid is an antibiotic that is also a non-selective monoamine oxidase (MAO) inhibitor. Since monoamine oxidase type A deaminates serotonin, administration of a non-selective MAO inhibitor concurrently with vortioxetine can lead to serious reactions including serotonin syndrome. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    Yohimbine: (Major) Avoid yohimbine during linezolid therapy and for 2 weeks after the discontinuation of linezolid. Linezolid is a reversible, non-selective monoamine oxidase inhibitor (MAOI). At high doses, yohimbine may nonselectively inhibit MAO and also, at normal doses, activates the sympathetic nervous system via selective central alpha 2-adrenoceptor antagonism. Some experts have cautioned against the combination of yohimbine with MAOIs and drugs with MAOI activity, since the activity of yohimbine might result in increased blood pressure or other serious side effects.

    PREGNANCY AND LACTATION

    Pregnancy

    Available data from published and postmarketing case reports with linezolid use during human pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. When administered to pregnant animals during organogenesis, linezolid did not cause malformations at maternal exposures up to 6.5 times the clinical therapeutic exposure based on AUCs. However, embryofetal lethality was observed at 6.5 times the estimated human exposure.[28599]

    Linezolid is present in breast milk. Based on available data, the daily dose of linezolid that the infant would receive from breast milk would be approximately 6% to 9% of the recommended therapeutic infant dose (10 mg/kg every 8 hours). There is no information on the effects of linezolid on the breast-fed infant; however, diarrhea and vomiting were the most common adverse reactions reported in clinical trials in infants receiving linezolid therapeutically. Advise breast-feeding women receiving linezolid to monitor the infant for diarrhea and vomiting. There is no information on the effects of linezolid on milk production. Consider the developmental and health benefits of breast-feeding along with the monther's clinical need for linezolid and any potential adverse effects on the breast-fed child from linezolid or the underlying maternal condition. Vancomycin, daptomycin, clindamycin, and sulfamethoxazole; trimethoprim may be potential alternatives to consider during breast-feeding. Site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Alternative antimicrobials that previous American Academy of Pediatrics (AAP) recommendations considered as usually compatible with breast-feeding include clindamycin and sulfamethoxazole; trimethoprim.

    MECHANISM OF ACTION

    Oxazolidinones exhibit a mechanism of action that is different from other antimicrobial classes. Linezolid inhibits bacterial protein synthesis by interfering with translation. Linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit; this action prevents the formation of a functional 70S initiation complex, an essential step in the bacterial translation process. Without proper protein production, susceptible bacteria cannot multiply. The action of linezolid is considered to be bacteriostatic against staphylococci and enterococci. Linezolid appears to be bactericidal against the majority of streptococcal strains tested. The predominant activity of linezolid is against aerobic gram-positive organisms. Linezolid exhibits little activity against aerobic gram-negative organisms or anaerobes in vitro; combination with other antimicrobial therapies may be clinically indicated if presumptive or documented pathogens include gram-negative or anaerobic bacteria.[28599] [51976] [51978]
     
    The susceptibility interpretive criteria for linezolid are delineated by pathogen. The MICs are defined for Staphylococcus sp. as susceptible at 4 mcg/mL or less and resistant at 8 mcg/mL or more. The MICs are defined for Enterococcus sp. as susceptible at 2 mcg/mL or less, intermediate at 4 mcg/mL (based on the known ability of linezolid to concentrate in the urine), and resistant at 8 mcg/mL or more. The MICs are defined for S. pneumoniae, beta-hemolytic Streptococcus sp., and S. viridans group as susceptible at 2 mcg/mL or less.[63320] [63321]
     
    Linezolid is also a reversible, non-selective inhibitor of monoamine oxidase (MAO).[28599]

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