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  • CLASSES

    Glycopeptide Antibiotics
    Intestinal Antibiotics
    Ophthalmological Anti-infectives

    DEA CLASS

    Rx

    DESCRIPTION

    Glycopeptide antibiotic; only effective for gram-positive bacteria; poorly absorbed orally; however, used orally to treat GI infections such as pseudomembranous colitis; serum concentration monitoring with systemic use.

    COMMON BRAND NAMES

    First-Vancomycin, FIRVANQ, Vancocin, VANCOSOL

    HOW SUPPLIED

    First-Vancomycin/FIRVANQ/Vancocin/Vancomycin/Vancomycin Hydrochloride Oral Pwd F/Recon: 3.8g, 3.84g, 5mL, 7.69g, 7.7g, 10.76g, 15.38g, 15.4g, 250mg
    Vancocin/Vancomycin/Vancomycin Hydrochloride Intravenous Inj Pwd F/Sol: 1g, 1.25g, 1.5g, 5g, 10g, 250mg, 500mg, 750mg
    Vancocin/Vancomycin/Vancomycin Hydrochloride Oral Cap: 125mg, 250mg
    Vancomycin/Vancomycin Hydrochloride Intraocular Sol: 1mL, 10mg
    Vancomycin/Vancomycin Hydrochloride Ophthalmic Sol: 1mL, 10mg
    Vancomycin/Vancomycin Hydrochloride/Vancomycin Hydrochloride, Dextrose/Vancomycin Hydrochloride, Sodium Chloride/Vancomycin, Dextrose/Vancomycin, Sodium Chloride Intravenous Inj Sol: 1mL, 5mg, 1-0.9%, 1-5%, 500-0.9%, 500-5%, 750-0.9%, 750-5%
    Vancomycin/Vancomycin Hydrochloride/VANCOSOL Intravenous Inj Pwd: 1g

    DOSAGE & INDICATIONS

    For the treatment of infective endocarditis.
    Intravenous dosage
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] [60294] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours.[40956] Adjust dose based on serum concentrations. Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL.[35013] [46693] Guidelines recommend vancomycin monotherapy for 4 weeks for native valve endocarditis (NVE) due to highly penicillin-susceptible Viridans group streptococci (VGS) and S. gallolyticus (bovis) infections or relatively penicillin-resistant VGS for patients unable to tolerate penicillins or ceftriaxone as well as penicillin-resistant VGS infections. Treat prosthetic valve endocarditis (PVE) caused by VGS for 6 weeks. Vancomycin may be used for 4 weeks for NVE and for 6 weeks for PVE caused by S. pneumoniae for patients intolerant of beta-lactams. Consider adding vancomycin and rifampin to cefotaxime or ceftriaxone for infections due to cefotaxime-resistant S. pneumoniae. Vancomycin for 4 to 6 weeks is an alternative for infections due to S. pyogenes in patients intolerant to beta-lactams. Vancomycin is also recommended for 6 weeks for NVE due to staphylococci for patients with anaphylactoid-type hypersensitivity reactions to beta-lactams or methicillin-resistant strains. Vancomycin plus rifampin for at least 6 weeks and gentamicin for 2 weeks is recommended for PVE caused by methicillin-resistant staphylococci. Use vancomycin plus gentamicin for 6 weeks for NVE or PVE due to penicillin-resistant Enterococcus in patients unable to tolerate a beta-lactam. For patients with acute (days) culture-negative NVE, vancomycin plus cefepime could be reasonable empiric therapy, and for patients with subacute (weeks) culture-negative NVE, vancomycin plus ampicillin; sulbactam could be reasonable empiric therapy. For patients with early (less than 1 year after surgery) culture-negative PVE, vancomycin plus cefepime, rifampin, and gentamicin could be reasonable empiric therapy, and for late culture-negative PVE, an initial treatment option could include ceftriaxone and vancomycin. Treat culture-negative endocarditis for 4 to 6 weeks.[60294]

    Children and Adolescents

    40 to 60 mg/kg/day IV divided every 6 to 12 hours is recommended by guidelines. Adjust dosage based on serum concentrations.[46693] [60295] A loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients.[46693] The FDA-approved dosage for pediatric patients is 40 mg/kg/day IV divided every 6 hours.[40937] Guidelines recommend gentamicin plus ampicillin; sulbactam with or without vancomycin for culture-negative, community-acquired native valve endocarditis (NVE) or late (more than 1 year after surgery) prosthetic valve endocarditis (PVE); alternately, vancomycin plus gentamicin may be used. Treat for 4 to 6 weeks for NVE and for 6 weeks with rifampin for PVE. Vancomycin plus gentamicin, cefepime, and rifampin (if prosthetic material is present) is recommended for culture-negative nosocomial endocarditis associated with vascular cannulae or early (less than 1 year after surgery) PVE; treat for 4 to 6 weeks, with a longer course for PVE. For endocarditis due to relatively penicillin-resistant streptococci, including enterococci, vancomycin, in combination with gentamicin for the first 2 weeks or the entire course for enterococci, is recommended as an alternative; vancomycin is also an alternative for streptococcal endocarditis highly susceptible to penicillin. For streptococcal endocarditis, treat for 4 weeks for NVE and 6 weeks for PVE; treat for 6 weeks for NVE and PVE due to enterococci. Vancomycin, with or without gentamicin for the first 3 to 5 days, is recommended for methicillin-resistant S. aureus endocarditis; vancomycin, with or without gentamicin for the first 3 to 5 days, is an alternative for staphylococcal endocarditis susceptible to or resistant to penicillin G. Add rifampin (for the entire course) plus gentamicin (for the first 2 weeks of therapy) for staphylococcal PVE. For native valve staphylococcal endocarditis susceptible to oxacillin, treat for 4 to 6 weeks. For native valve staphylococcal endocarditis resistant to oxacillin or prosthetic valve staphylococcal endocarditis, treat for at least 6 weeks.[60295]

    Infants

    60 mg/kg/day IV divided every 6 hours in combination with appropriate antimicrobial therapy depending on causative microorganism is recommended by guidelines. A loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients. Adjust dosage based on serum concentrations.[46693] The FDA-approved dosage for pediatric patients is 40 mg/kg/day IV divided every 6 hours.[40937]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    For the treatment of pseudomembranous colitis due to C. difficile infection.
    For the treatment of initial episode of pseudomembranous colitis due to C. difficile infection and first recurrence in patients previously treated with metronidazole.
    Oral dosage
    Adults

    125 mg PO 4 times daily for 10 days as a first-line therapy.[28468] [62844] [62877]

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 125 mg/dose) PO 4 times daily for 10 days as a first line therapy. The FDA-approved dose is 40 mg/kg/day (Max: 2 g/day) PO divided 3 to 4 times daily for 7 to 10 days.

    For the treatment of fulminant pseudomembranous colitis due to C. difficile infection.
    Oral dosage
    Adults

    500 mg PO or via nasogastric tube 4 times daily with IV metronidazole. If clinical improvement after 48 to 72 hours, consider decreasing the dose to 125 mg PO every 6 hours for 10 days. If an ileus is present, consider adding vancomycin as a retention enema.[62877]

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO 4 times daily for 10 days; consider adding metronidazole IV.

    Rectal dosage†
    Adults

    500 mg in 100 mL of 0.9% Sodium Chloride Injection per rectum every 6 hours as adjunctive therapy if ileus present. Other dosing regimens have been described in case reports including 500 mg every 4 hours and 1 g every 8 to 12 hours. Volumes of 250 to 500 mL of 0.9% Sodium Chloride Injection have also been described. Decompression of the megacolon may also be beneficial.

    Infants, Children, and Adolescents

    Rectal vancomycin is suggested as adjunctive therapy; however, very limited dosing data are available.  A case report in a 4-year-old boy with toxic megacolon due to C. difficile infection describes the use of rectal vancomycin 125 mg in 25 mL of 0.9% Sodium Chloride Injection 4 times daily for 1 month. Decompression of the megacolon may also be beneficial.  A rectal vancomycin dose of 500 mg in 100 mL of 0.9% Sodium Chloride Injection every 6 hours is recommended in adults. Other dosing regimens have been described in case reports in adults including 500 mg every 4 hours and 1 g every 8 to 12 hours. These doses/volume (i.e., 500 mg in 100 mL of 0.9% Sodium Chloride Injection) may be acceptable for older children and adolescents of appropriate weight.

    For the treatment of first recurrence of pseudomembranous colitis due to C. difficile infection in patients initially treated with vancomycin, metronidazole, or fidaxomicin.
    Oral dosage
    Adults

    125 mg PO 4 times daily for 10 to 14 days, then 125 mg PO 2 times daily for 1 week, then 125 mg PO once daily for 1 week, then 125 mg PO every 2 to 3 days for 2 to 8 weeks, or alternately, 125 mg PO 4 times daily for 10 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 125 mg/dose) PO 4 times daily for 10 days.

    For the treatment of second/subsequent episodes of pseudomembranous colitis due to C. difficile infection.
    Oral dosage
    Adults

    125 mg PO 4 times daily for 10 days followed by rifaximin for 20 days, or 125 mg PO 4 times daily for 10 to 14 days, then 125 mg PO 2 times daily for 1 week, then 125 mg PO once daily for 1 week, then 125 mg PO every 2 to 3 days for 2 to 8 weeks.[62877] A 6-week tapered regimen has also been successful; 125 mg PO 4 times daily for 1 week, then 125 mg PO twice daily for 1 week, then 125 mg PO once daily for 1 week, then 125 mg PO every other day for 1 week, then 125 mg PO every 3 days for 2 weeks.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO 4 times daily for 10 days followed by rifaximin for 20 days, or 10 mg/kg/dose (Max: 125 mg/dose) PO 4 times daily for 10 to 14 days, then 10 mg/kg/dose (Max: 125 mg/dose) PO 2 times daily for 1 week, then 10 mg/kg/dose (Max: 125 mg/dose) PO once daily for 1 week, then 10 mg/kg/dose (Max: 125 mg/dose) PO every 2 to 3 days for 2 to 8 weeks.

    For the treatment of third/subsequent episodes of pseudomembranous colitis due to C. difficile infection prior to fecal microbiota transplantation.
    Oral dosage
    Adults

    125 mg PO 4 times daily for 10 days.

    For the treatment of pseudomembranous colitis due to C. difficile infection in patients with inflammatory bowel disease (IBD).
    Oral dosage
    Adults

    125 mg PO 4 times daily for at least 14 days.

    For secondary C. difficile infection prophylaxis (i.e., long-term suppressive therapy)†.
    Oral dosage
    Adults

    125 mg PO once daily. May increase dose to 125 mg PO 2 or 3 times daily if patients continue to experience loose stools at lower doses. Secondary prophylaxis may be considered in patients who are not candidates for fecal microbiota transplantation, relapsed after fecal microbiota transplantation, require ongoing or frequent antibiotic courses, or are at high risk of recurrence during systemic antibiotic use.

    For the treatment of enterocolitis due to S. aureus.
    Oral dosage
    Adults

    500 mg to 2 g/day PO divided 3 to 4 times daily for 7 to 10 days.

    Infants, Children, and Adolescents

    40 mg/kg/day (Max: 2 g/day) PO divided 3 to 4 times daily for 7 to 10 days.

    For the treatment of bacteremia and sepsis.
    Intravenous dosage (Intermittent IV Infusion)
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines. The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose. Start within 1 hour of recognition as part of empiric multi-drug therapy. Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations. 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 MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia. The addition of gentamicin or rifampin is not recommended for bacteremia.

    Infants, Children, and Adolescents

    60 mg/kg/day IV divided every 6 hours is recommended by the Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg may be considered in seriously ill patients.[46693] Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV divided every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy.[40937] [41051] [41052] [41053] [41054] Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.[54911] 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] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] 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] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] 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] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] 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] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 2 weeks for uncomplicated bacteremia and 4 to 6 weeks for complicated bacteremia.[46693]

    Intravenous dosage (Continuous IV Infusion)†

    NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

    Infants, Children, and Adolescents

    A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

    Neonates

    A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations.

    For the treatment of serious gram-positive infections, including skin and skin structure infections, such as cellulitis.
    Intravenous dosage (Intermittent IV Infusion)
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose.[40956] Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations.[35013] [46693] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Infants, Children, and Adolescents

    60 mg/kg/day IV divided every 6 hours is recommended by the Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients.[46693] Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV divided every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy.[40937] [41051] [41052] [41053] [41054] Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.[54911] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for 7 to 14 days for complicated skin and skin structure infections.[46693]

    Intravenous dosage (Continuous IV Infusion)†

    NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

    Infants, Children, and Adolescents

    A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

    Neonates

    A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

    For the treatment of mastitis.
    Intravenous dosage
    Adults

    15 mg/kg/dose IV every 12 hours for 10 to 14 days.

    For the treatment of neonatal mastitis.
    Intravenous dosage
    Infants 1 to 2 months

    40 to 60 mg/kg/day IV divided every 6 hours. [57437] [63245] [64275]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours.[57437] [63245] [64275]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours.[57437] [63245] [64275]

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours.[57437] [63245] [64275]

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours.[57437] [63245] [64275]

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours.[57437] [63245] [64275]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours.[57437] [63245] [64275]

    For the treatment of serious gram-positive infections, including lower respiratory tract infections (LRTIs) such as community-acquired pneumonia (CAP), nosocomial pneumonia, and pleural empyema†.
    For the treatment of nonspecific lower respiratory tract infections (LRTIs).
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. The FDA-approved dose is 500 mg IV every 6 hours or 1 g IV every 12 hours.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. The FDA-approved dose is 500 mg IV every 6 hours or 1 g IV every 12 hours.

    Children and Adolescents 12 to 17 years

    60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients. The FDA-approved dose is 40 mg/kg/day IV divided every 6 hours.

    Obese Children and Adolescents 12 to 17 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. The FDA-approved dose is 40 mg/kg/day IV divided every 6 hours.

    Infants and Children 3 months to 11 years

    60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg IV in critically ill patients. The FDA-approved dose is 40 mg/kg/day IV divided every 6 hours.

    Obese Infants and Children 3 months to 11 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. The FDA-approved dose is 40 mg/kg/day IV divided every 6 hours.

    Infants 1 to 2 months

    45 to 60 mg/kg/day IV divided every 6 to 8 hours; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients. The FDA-approved dose is 40 mg/kg/day IV divided every 6 hours.

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter.[63245] The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter.[63245] The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter.[63245] The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] 

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter.[63245] The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter.[63245] The FDA-approved dose is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[63969] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587]

    Continuous Intravenous Infusion dosage†

    NOTE: Guidelines recommend that continuous infusion regimens may be a reasonable alternative when the AUC target cannot be achieved with conventional intermittent infusion dosing.[65262]

    Adults

    15 to 20 mg/kg/dose IV loading dose, followed by 30 to 60 mg/kg/day continuous IV infusion to achieve a steady-state concentration of 20 to 25 mg/L.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose IV loading dose, followed by continuous IV infusion of 30 to 60 mg/kg/day IV to achieve a steady-state concentration of 15 to 25 mcg/mL. Pediatric patients younger than 8 years have been shown to require higher doses than older patients to achieve target vancomycin serum concentrations. In a study in 240 pediatric patients (age 31 days and older) converted to a continuous infusion regimen, the mean doses required to achieve a vancomycin serum concentration of 15 to 20 mg/L were approximately 50 mg/kg/day IV in patients 8 years and younger and approximately 45 mg/kg/day IV in patients older than 8 years.

    Neonates

    10 to 15 mg/kg/dose IV loading dose, followed by 15 to 40 mg/kg/day continuous IV infusion, based on postmenstrual age and renal function, to achieve a steady-state concentration of 15 to 25 mcg/mL. Study data have shown that continuous infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations.

    For the treatment of community-acquired pneumonia (CAP).
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat 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. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat 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. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Children and Adolescents 12 to 17 years

    60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Children and Adolescents 12 to 17 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants and Children 3 months to 11 years

    60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Infants and Children 3 months to 11 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants 1 to 2 months

    45 to 60 mg/kg/day IV divided every 6 to 8 hours; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Continuous Intravenous Infusion dosage†

    NOTE: Guidelines recommend that continuous infusion regimens may be a reasonable alternative when the AUC target cannot be achieved with conventional intermittent infusion dosing.

    Adults

    15 to 20 mg/kg/dose IV loading dose, followed by 30 to 60 mg/kg/day continuous IV infusion to achieve a steady-state concentration of 20 to 25 mg/L. Treat 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. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose IV loading dose, followed by continuous IV infusion of 30 to 60 mg/kg/day IV to achieve a steady-state concentration of 15 to 25 mcg/mL. Pediatric patients younger than 8 years have been shown to require higher doses than older patients to achieve target vancomycin serum concentrations. In a study in 240 pediatric patients (age 31 days and older) converted to a continuous infusion regimen, the mean doses required to achieve a vancomycin serum concentration of 15 to 20 mg/L were approximately 50 mg/kg/day IV in patients 8 years and younger and approximately 45 mg/kg/day IV in patients older than 8 years. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates

    10 to 15 mg/kg/dose IV loading dose, followed by 15 to 40 mg/kg/day continuous IV infusion, based on postmenstrual age and renal function, to achieve a steady-state concentration of 15 to 25 mcg/mL. Study data have shown that continuous infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    For the treatment of nosocomial pneumonia.
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for 7 days as part of combination therapy. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for 7 days as part of combination therapy. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Children and Adolescents 12 to 17 years

    60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Children and Adolescents 12 to 17 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants and Children 3 months to 11 years

    60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Obese Infants and Children 3 months to 11 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants 1 to 2 months

    45 to 60 mg/kg/day IV divided every 6 to 8 hours; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Continuous Intravenous Infusion dosage†

    NOTE: Guidelines recommend that continuous infusion regimens may be a reasonable alternative when the AUC target cannot be achieved with conventional intermittent infusion dosing.

    Adults

    15 to 20 mg/kg/dose IV loading dose, followed by 30 to 60 mg/kg/day continuous IV infusion to achieve a steady-state concentration of 20 to 25 mg/L. Treat for 7 days as part of combination therapy. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Infants, Children, and Adolescents

    10 to 20 mg/kg/dose IV loading dose, followed by continuous IV infusion of 30 to 60 mg/kg/day IV to achieve a steady-state concentration of 15 to 25 mcg/mL. Pediatric patients younger than 8 years have been shown to require higher doses than older patients to achieve target vancomycin serum concentrations. In a study in 240 pediatric patients (age 31 days and older) converted to a continuous infusion regimen, the mean doses required to achieve a vancomycin serum concentration of 15 to 20 mg/L were approximately 50 mg/kg/day IV in patients 8 years and younger and approximately 45 mg/kg/day IV in patients older than 8 years. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    Neonates

    10 to 15 mg/kg/dose IV loading dose, followed by 15 to 40 mg/kg/day continuous IV infusion, based on postmenstrual age and renal function, to achieve a steady-state concentration of 15 to 25 mcg/mL. Study data have shown that continuous infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations. MRSA guidelines recommend a treatment duration of 7 to 21 days.

    For the treatment of hospital-acquired or postprocedural pleural empyema†.
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for a minimum of 2 weeks after drainage and defervescence as part of combination therapy.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for a minimum of 2 weeks after drainage and defervescence as part of combination therapy.

    Continuous Intravenous Infusion dosage†

    NOTE: Guidelines recommend that continuous infusion regimens may be a reasonable alternative when the AUC target cannot be achieved with conventional intermittent infusion dosing.

    Adults

    15 to 20 mg/kg/dose IV loading dose, followed by 30 to 60 mg/kg/day continuous IV infusion to achieve a steady-state concentration of 20 to 25 mg/L. Treat for a minimum of 2 weeks after drainage and defervescence as part of combination therapy.

    For surgical infection prophylaxis†.
    Intravenous dosage
    Adults

    15 mg/kg/dose IV as a single dose within 120 minutes prior to the surgical incision. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Vancomycin is recommended as alternate therapy for patients with beta-lactam allergy undergoing cardiothoracic, hernia repair, neurosurgical, orthopedic, clean urologic, vascular, heart or lung transplantation, and plastic surgery procedures. Vancomycin is also recommended in combination with another appropriate antimicrobial (i.e., aminoglycoside, aztreonam, or fluoroquinolone) as alternate therapy for patients with beta-lactam allergy undergoing gastroduodenal, biliary tract, hysterectomy, urologic with prosthesis, and abdominal transplantation procedures.

    Infants, Children, and Adolescents

    15 mg/kg/dose IV as a single dose within 120 minutes prior to the surgical incision. No intraoperative redosing and a duration of prophylaxis less than 24 hours for most procedures are recommended. A longer prophylaxis duration of 48 hours for certain cardiothoracic procedures is controversial. Vancomycin is recommended as alternate therapy for patients with beta-lactam allergy undergoing cardiothoracic, hernia repair, neurosurgical, orthopedic, clean urologic, vascular, heart or lung transplantation, and plastic surgery procedures. Vancomycin is also recommended in combination with another appropriate antimicrobial (i.e., aminoglycoside, aztreonam, or fluoroquinolone) as alternate therapy for patients with beta-lactam allergy undergoing gastroduodenal, biliary tract, urologic with prosthesis, and abdominal transplantation procedures.

    For the treatment of CNS infections†, including meningitis†, ventriculitis† (including shunt-related infections), brain abscess†, subdural empyema†, spinal epidural abscess†, and septic thrombosis of the cavernous or dural venous sinus†.
    Intravenous dosage
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours. Adjust doses based on serum concentrations.[38764] [46693] Doses should be aggressive due to the relatively poor penetration of vancomycin into cerebral spinal fluid (CSF). Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat with or without rifampin for 10 to 14 days depending on causative microorganism and clinical response.[32690] [46693] [61814] For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.[46693]

    Infants, Children, and Adolescents

    15 mg/kg/dose IV every 6 hours; adjust dosage based on serum concentrations. A loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients. Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response.[32690] [46693] [61814] For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.[46693] Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years), the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.[54911]

    Neonates 8 days and older weighing more than 2 kg

    15 mg/kg/dose IV every 6 to 8 hours. A loading dose of 20 mg/kg IV may be used prior to the maintenance dose. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response. For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.

    Neonates 8 days and older weighing 1.2 to 2 kg

    15 mg/kg/dose IV every 8 to 12 hours. A loading dose of 20 mg/kg IV may be used prior to the maintenance dose. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response. For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.

    Neonates 8 days and older weighing less than 1.2 kg

    15 mg/kg/dose IV every 24 hours.[51871] A loading dose of 20 mg/kg IV may be used prior to the maintenance dose.[63245] Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response.[32690] [46693] [61814] For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.[46693]

    Neonates 0 to 7 days weighing more than 2 kg

    15 mg/kg/dose IV every 8 to 12 hours. A loading dose of 20 mg/kg IV may be used prior to the maintenance dose. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response. For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.

    Neonates 0 to 7 days weighing 1.2 to 2 kg

    15 mg/kg/dose IV every 12 to 18 hours. A loading dose of 20 mg/kg IV may be used prior to the maintenance dose. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin- and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response. For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.

    Neonates 0 to 7 days weighing less than 1.2 kg

    15 mg/kg/dose IV every 24 hours.[51871] A loading dose of 20 mg/kg IV may be used prior to the maintenance dose.[63245] Guidelines recommend vancomycin in combination with appropriate antimicrobial therapy for CNS infections due to highly penicillin and cephalosporin-resistant Streptococcus pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and Enterococcus species. For meningitis, treat for 10 to 14 days depending on causative microorganism and clinical response.[32690] [46693] [61814] For other MRSA-associated CNS infections (i.e., brain abscess, subdural empyema, spinal epidural abscess, and septic thrombosis of cavernous or dural venous sinus), treat for 4 to 6 weeks.[46693]

    Intrathecal or Intraventricular dosage (preservative-free formulations only)
    Adults

    5 to 20 mg/day intrathecally or intraventricularly is recommended; however, most studies have used a 10 mg or 20 mg dose. Use in addition to systemic vancomycin therapy. For intraventricular administration, dosage and frequency may vary depending on ventricle size and external ventricular output. Dosage may also be adjusted as necessary based on vancomycin CSF concentrations and MIC of the organism.

    Infants, Children, and Adolescents

    5 to 20 mg/day intrathecally or intraventricularly is recommended; however, most studies have used a 10 mg or 20 mg dose.[32690] [61814] Use in addition to systemic vancomycin therapy. Adjust dose as necessary based on vancomycin CSF concentrations, MIC of the organism, ventricular size, and output from ventricular drain.[61814]

    For vancomycin desensitization† in patients with vancomycin hypersensitivity who require vancomycin therapy.
    NOTE: Several vancomycin desensitization protocols have been reported in the literature and are based on case reports or small case series.[27463] A couple of methods are described below.
    For rapid vancomycin desensitization† (Lerner and Dwyer protocol).
    Intravenous dosage
    Adults

    Administer 5 infusions in succession at an initial rate of 30 mL/hour and increase by 30 mL/hour as tolerated every 5 minutes (Max: 300 mL/hour). Infusion 1: 0.02 mg/100 mL IV; Infusion 2: 0.2 mg/100 mL IV; Infusion 3: 2 mg/100 mL IV; Infusion 4: 20 mg/100mL IV; Infusion 5: 500 mg/250 mL IV. Immediately administer the required vancomycin dose after Infusion 5. If the patient does not tolerate an infusion, stop the infusion and reinfuse at the previously tolerated infusion at the highest tolerated rate; may repeat this step up to 3 times for any given concentration.[27461] [27463]

    For slow vancomycin desensitization† (Lin protocol).
    Intravenous dosage
    Adults

    Administer 1 infusion on 6 consecutive days at a rate of 100 mL/hour. Infusion 1: 0.5 mg/500 mL IV; Infusion 2: 5 mg/500 mL IV; Infusion 3: 50 mg/500 mL IV; Infusion 4: 50 mg/500 mL IV; Infusion 5: 250 mg/500 mL IV; Infusion 6: 500 mg/500 mL IV. Administer the required vancomycin dose on day 7.

    For perinatal Group B streptococcal infection prophylaxis† in patients allergic to penicillins and cephalosporins.
    Intravenous dosage
    Pregnant Females

    20 mg/kg/dose (Max: 2 g/dose) IV every 8 hours intrapartum as an alternative in patients with a high-risk penicillin allergy infected with a clindamycin-resistant Group B Streptococcus isolate.[64407]

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

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose.[40956] Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations.[35013] [46693] For MRSA, IDSA suggests that 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; however, 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.[46693]

    Infants, Children, and Adolescents

    60 mg/kg/day IV divided every 6 hours is recommended by the Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients.[46693] Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV divided every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy.[40937] [41051] [41052] [41053] [41054] Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.[54911] For MRSA, treat for at least 4 to 6 weeks.[46693]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 4 to 6 weeks.[46693]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 4 to 6 weeks.

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 4 to 6 weeks.

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 4 to 6 weeks.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 4 to 6 weeks.

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 4 to 6 weeks.[46693]

    Intravenous dosage (Continuous IV Infusion)†

    NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

    Infants, Children, and Adolescents

    A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

    Neonates

    A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

    For the treatment of septic arthritis.
    Intravenous dosage
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose.[40956] Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations.[35013] [46693] For MRSA, treat for at least 3 to 4 weeks.[46693]

    Infants, Children, and Adolescents

    60 mg/kg/day IV divided every 6 hours is recommended by the Infectious Diseases Society of America (IDSA) for infections caused by methicillin-resistant Staphylococcus aureus (MRSA); a loading dose of 20 to 25 mg/kg IV may be considered in seriously ill patients.[46693] Monitor serum concentrations and adjust dosage accordingly. The FDA-approved dosage is 40 mg/kg/day IV divided every 6 hours; however, this dose may provide subtherapeutic concentrations in many pediatric patients. In general, higher doses may be required for certain at risk populations such as ICU patients, patients with invasive MRSA infections, and those with malignancy.[40937] [41051] [41052] [41053] [41054] Based on the results of a pharmacokinetic study (n = 702, age 3 months to 21 years) the following age-based doses were required to attain a target AUC/MIC of at least 400 (recommended for empiric therapy of serious MRSA infections) in 75% of non-obese pediatric patients with normal renal function: 3 months to 1 year: 70 mg/kg/day IV divided every 6 hours; 2 years and older: 60 mg/kg/day IV divided every 6 hours; consider 70 mg/kg/day if SCr is less than 0.45 mg/dL or if more than 30% MRSA isolates have MICs of 1.5 mcg/mL or higher. Clinical outcomes were not assessed in this study.[54911] For MRSA, treat for at least 3 to 4 weeks.[46693]

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 3 to 4 weeks.[46693]

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 3 to 4 weeks.

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 3 to 4 weeks.

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours is recommended by the American Academy of Pediatrics (AAP). The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours. The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. For MRSA, treat for at least 3 to 4 weeks.

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 3 to 4 weeks.[46693]

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours is recommended by the American Academy of Pediatrics (AAP).[63245] The FDA-approved dosage is 15 mg/kg/dose IV initially, then 10 mg/kg/dose IV every 12 hours for the first week of life, then increase to every 8 hours.[40937] The dosing interval of vancomycin may need to be extended in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] For MRSA, treat for at least 3 to 4 weeks.[46693]

    Intravenous dosage (Continuous IV Infusion)†

    NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions in adult patients; the role of continuous infusion administration in pediatric patients is unclear.

    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients.

    Infants, Children, and Adolescents

    A standard continuous infusion (CI) dosing regimen has not been established and data are limited in pediatric patients. Doses of 30 to 60 mg/kg/day IV infused continuously over 24 hours have been used in limited case reports and studies. For infants and adolescents, a CI dose of 40 mg/kg/day IV may be optimal compared to higher doses (55 to 60 mg/kg/day) in children; although empiric initial doses less than 40 mg/kg/day IV may be needed in adolescents. Doses of 30 to 40 mg/kg/day IV by continuous infusion have been used in studies in adults. Pediatric patients (older than 6 months, n = 16) converted to a vancomycin CI regimen at 55 to 60 mg/kg/day IV had a mean initial plateau serum vancomycin concentration (SVC) of 20.2 mg/L within 24 to 48 hours after conversion; mean of all SVCs was 19.1 mg/L. The range of doses necessary to achieve a target plateau SVC of 15 mg/L was 23.8 to 65.4 mg/kg/day with a mean dose of 44.3 +/- 12. 8 mg/kg/day and median dose of 41 mg/kg/day. No patients developed nephrotoxicity during the study.

    Neonates

    A standard continuous infusion dosing regimen has not been established. Loading doses of 7 to 15 mg/kg/dose IV administered over 1 to 2 hours followed by initial continuous infusions of 10 to 50 mg/kg/day IV based on weight, postconceptional age, gestational age, and/or serum creatinine have been studied. Doses were adjusted to maintain serum vancomycin concentrations of 10 to 30 mcg/mL at steady-state. Study data have shown that continuous vancomycin infusions are well tolerated in neonates and they may also result in improved achievement of optimal target concentrations.

    For the treatment of prosthetic joint infections.
    Intravenous dosage
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose.[40956] Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations.[35013] [46693] For MRSA, the IDSA recommends the addition of 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.[46693]

    Intravenous dosage (Continuous IV Infusion)†
    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients. NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions.

    For the treatment of spinal implant infections.
    Intravenous dosage
    Adults

    25 to 30 mg/kg (actual body weight) IV loading dose for seriously-ill patients, then 15 to 20 mg/kg/dose (actual body weight) IV every 8 to 12 hours per guidelines.[35013] [46693] The FDA-approved dosage is 500 mg IV every 6 hours or 1 g IV every 12 hours. Patient factors, such as age or obesity, may call for modification of the usual daily dose.[40956] Doses are not likely to achieve successful outcomes if S. aureus MICs are more than 1 mcg/mL. Adjust dose based on serum concentrations.[35013] [46693] For MRSA, the IDSA recommends the addition of 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 with or without 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.[46693]

    Intravenous dosage (Continuous IV Infusion)†
    Adults

    There is no standard continuous infusion dose. Two studies used a loading dose of 15 mg/kg IV infused over 60 minutes, adjusted based on baseline serum creatinine, then 30 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 15 to 25 mg/L. Changes in doses were made in 500 mg increments. One additional study used a loading dose of 20 mg/kg IV infused over 60 minutes, then 40 mg/kg IV infused continuously over 24 hours. Serum concentrations were obtained to guide dosage adjustments to achieve plateau concentrations of 20 to 25 mg/L for bone infections. Changes in doses were made in 500 mg increments. Pea and colleagues have further developed their standard 30 mg/kg/day IV infusion into 2 distinct nomograms based on creatinine clearance to achieve either a 15 mg/L or 20 mg/L plateau concentration in critically ill patients. NOTE: ASHP, IDSA, and SIDP state that continuous infusion vancomycin holds no advantage over intermittent infusions.

    For the empiric treatment of febrile neutropenia†.
    Intravenous dosage
    Adults

    500 mg to 1,000 mg IV every 8 to 12 hours or 15 mg/kg IV every 12 hours has been studied. Guidelines suggest 15 to 20 mg/kg (based on actual body weight) IV every 8 to 12 hours in patients with normal renal function. Doses should be adjusted based on serum concentrations. Febrile neutropenia guidelines suggest vancomycin should be added in patients at increased risk for MRSA or enterococcal infections.

    For the treatment of intraabdominal infections†, including peritonitis†, appendicitis†, intraabdominal abscess†, biliary tract infections†, neonatal necrotizing enterocolitis†, spontaneous bacterial peritonitis†, and peritoneal dialysis-related peritonitis†.
    For the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections† with adequate source control.
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Children and Adolescents 12 to 17 years

    60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Obese Children and Adolescents 12 to 17 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Infants and Children 3 months to 11 years

    60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg IV in critically ill patients. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Obese Infants and Children 3 months to 11 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day); adjust dose based on target PK/PD parameter. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Infants 1 to 2 months

    45 to 60 mg/kg/day IV divided every 6 to 8 hours; adjust dose based on target PK/PD parameter. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Neonates older than 28 weeks gestation and SCr less than 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Neonates older than 28 weeks gestation and SCr 0.7 to 0.9 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Neonates older than 28 weeks gestation and SCr 1 to 1.2 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Neonates 28 weeks gestation and younger and SCr less than 0.5 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 12 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Neonates 28 weeks gestation and younger and SCr 0.5 to 0.7 mg/dL

    20 mg/kg/dose IV loading dose, followed by 20 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Neonates 28 weeks gestation and younger and SCr 0.8 to 1 mg/dL

    20 mg/kg/dose IV loading dose, followed by 15 mg/kg/dose IV every 24 hours; adjust dose based on target PK/PD parameter. The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

    Continuous Intravenous Infusion dosage

    NOTE: Guidelines recommend that continuous infusion regimens may be a reasonable alternative when the AUC target cannot be achieved with conventional intermittent infusion dosing.

    Adults

    15 to 20 mg/kg/dose IV loading dose, followed by 30 to 60 mg/kg/day continuous IV infusion to achieve a steady-state concentration of 20 to 25 mg/L. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Infants, Children, and Adolescents

    10 to 15 mg/kg/dose (20 mg/kg/dose in critically ill patients) IV loading dose, followed by continuous IV infusion of 30 to 60 mg/kg/day IV to achieve a steady-state concentration of 15 to 25 mcg/mL. Pediatric patients younger than 8 years have been shown to require higher doses than older patients to achieve target vancomycin serum concentrations. In a study in 240 pediatric patients (aged 31 days and older) converted to a continuous infusion regimen, the mean doses required to achieve a vancomycin serum concentration of 15 to 20 mg/L were approximately 50 mg/kg/day IV in patients 8 years and younger and approximately 45 mg/kg/day IV in patients older than 8 years. Treat for 3 to 7 days as part of combination therapy. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

    Neonates

    10 to 15 mg/kg/dose IV loading dose, followed by 15 to 40 mg/kg/day continuous IV infusion, based on postmenstrual age and renal function, to achieve a steady-state concentration of 15 to 25 mcg/mL. Study data have shown that continuous infusions are well tolerated in neonates and may also result in improved achievement of optimal target concentrations. Treat for 7 to 10 days as part of combination therapy. Vancomycin is an option for necrotizing enterocolitis.

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

    15 to 30 mg/kg/dose intraperitoneally every 5 to 7 days; adjust dose based on serum concentration target of more than 15 mcg/mL. Supplemental doses may be needed for automated PD. Treat for 14 to 21 days.

    Infants, Children, and Adolescents

    30 mg/kg/dose intraperitoneally once, followed by 15 mg/kg/dose every 3 to 5 days; adjust dose based on serum concentration and redose when less than 15 mcg/mL. Treat for 14 to 21 days.

    Continuous Intraperitoneal dosage†
    Adults

    30 mg/kg/bag intraperitoneal loading dose, followed by 1.5 mg/kg/bag in each dialysate exchange. Treat for 14 to 21 days.

    Infants, Children, and Adolescents

    1,000 mg/L intraperitoneal loading dose, followed by 25 mg/L in each dialysate exchange. Treat for 14 to 21 days.

    For the treatment of uncomplicated intraabdominal infections†.
    Intravenous dosage
    Adults

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours. Consider loading dose in critically ill patients. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day). Consider loading dose in critically ill patients. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Children and Adolescents 12 to 17 years

    60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day). Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg (Max: 3,000 mg/dose) IV in critically ill patients. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Obese Children and Adolescents 12 to 17 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 70 mg/kg/day IV divided every 6 to 8 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day). Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Infants and Children 3 months to 11 years

    60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day). Data are insufficient to recommend a loading dose in nonobese pediatric patients; however, based on adult studies, consider loading dose of 20 to 35 mg/kg IV in critically ill patients. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Obese Infants and Children 3 months to 11 years

    20 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 60 to 80 mg/kg/day IV divided every 6 hours (Usual Max: 3,000 mg/day; may require up to 3,600 mg/day). Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Infants 1 to 2 months

    45 to 60 mg/kg/day IV divided every 6 to 8 hours. Consider loading dose of 20 to 35 mg/kg IV in critically ill patients. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

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

    20 to 35 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours; adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for at least 5 to 7 days.

    Obese Adults

    20 to 25 mg/kg/dose (Max: 3,000 mg/dose) IV loading dose, followed by 15 to 20 mg/kg/dose IV every 8 to 12 hours (Usual Max: 4,500 mg/day); adjust dose based on target PK/PD parameter. Consider loading dose in critically ill patients. Treat for at least 5 to 7 days.

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

    60 mg/kg/day IV divided every 8 hours. Maintain vancomycin serum trough concentrations of 15 to 20 mg/L. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in adults. 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.

    Infants, Children, and Adolescents

    60 mg/kg/day IV divided every 8 hours. Adjust dose based on target PK/PD parameter. Vancomycin, in combination with appropriate antimicrobial therapy, is an alternative therapy for the treatment of systemic anthrax infection. For systemic infection without CNS involvement, dual combination IV therapy with vancomycin and a protein synthesis inhibitor (i.e., clindamycin, linezolid) is recommended. For documented or suspected CNS infection, triple IV therapy with vancomycin, a fluoroquinolone, and a protein synthesis inhibitor is recommended. For systemic infection in which meningitis can be excluded, treatment should continue for at least 14 days or until clinical criteria for improvement are met. 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. Prophylaxis to complete an antimicrobial course of up to 60 days will be required in both cases.[57108]

    Neonates 32 weeks gestation and older and SCr less than 0.7 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 12 hours.[57108] [63245] The dosing of vancomycin may need to be adjusted in neonatal patients on ECMO; doses of 20 mg/kg/dose IV every 18 to 24 hours have been suggested.[51586] [51587] Adjust dose based on target PK/PD parameter. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in neonates. 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.[57108]

    Neonates 32 weeks gestation and older and SCr 0.7 to 0.9 mg/dL

    20 mg/kg IV loading dose, followed by 20 mg/kg/dose IV every 24 hours.[57108] [63245] Adjust dose based on target PK/PD parameter. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in neonates. 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.[57108]

    Neonates 32 weeks gestation and older and SCr 1 to 1.2 mg/dL

    20 mg/kg IV loading dose, followed by 15 mg/kg/dose IV every 24 hours.[57108] [63245] Adjust dose based on target PK/PD parameter. Vancomycin, in combination with a protein synthesis inhibitor (i.e., clindamycin, linezolid), is an alternative therapy for the treatment of systemic anthrax infection without CNS involvement in neonates. 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.[57108]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2 g/day IV/PO per FDA-approved labeling; individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

    Geriatric

    2 g/day IV/PO per FDA-approved labeling; individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

    Adolescents

    40 mg/kg/day IV and 2 g/day PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

    Children

    40 mg/kg/day IV and 2 g/day PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

    Infants

    40 mg/kg/day IV/PO per FDA-approved product labeling; however, initial doses up to 60 mg/kg/day IV are recommended off-label for severe infections. Individualize IV dosage to patient age, weight, indication for use, and serum drug concentration monitoring.

    Neonates

    8 days and older: 30 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.
    0 to 7 days: 20 mg/kg/day IV per FDA-approved product labeling; however, doses should be individualized based on patient age, weight, indication for use, and serum drug concentration monitoring.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Oral dosing
    Specific guidelines for dosage adjustments of the oral formulation in renal impairment are not available; it appears no dosage adjustment is needed.[28468] [62844]
     
    Intravenous dosing
    The manufacturer's renal adjustment recommendations and conventional IV dosing nomograms will likely not lead to an appropriate AUC/MIC target of 400 to 600 mg x hour/L as defined by guidelines. Individualize IV dosage based on patient-specific factors and modify based on therapeutic drug monitoring.[65262]
     
    Adult patients† [65347] [65348] [65349]
    CrCl more than 65 mL/min per 70 kg: No dosage adjustment necessary.
    CrCl 40 to 65 mL/min per 70 kg: Extend IV dosing interval to every 12 hours.
    CrCl 20 to 39 mL/min per 70 kg: Extend IV dosing interval to every 24 hours.
    CrCl 10 to 20 mL/min per 70 kg: Extend IV dosing interval to every 48 hours.
     
    Infants, Children, and Adolescents† [32569]
    GFR more than 50 mL/minute/1.73 m2: No initial adjustment; monitor serum concentrations.
    GFR 30 to 50 mL/minute/1.73 m2: Extend IV dosing interval to every 12 hours
    GFR 10 to 29 mL/minute/1.73 m2: Extend IV dosing interval to every 18 to 24 hours.
    GFR less than 10 mL/minute/1.73 m2: Dose as needed per serum concentration monitoring.
    Neonates older than 28 weeks gestation† [63245]
    SCr less than 0.7 mg/dL: 15 mg/kg/dose IV every 12 hours.
    SCr 0.7 to 0.9 mg/dL: 20 mg/kg/dose IV every 24 hours.
    SCr 1 to 1.2 mg/dL: 15 mg/kg/dose IV every 24 hours.
    SCr 1.3 to 1.6 mg/dL: 10 mg/kg/dose IV every 24 hours.
    SCr more than 1.6 mg/dL: 15 mg/kg/dose IV every 48 hours.
     
    Neonates 28 weeks gestation and younger† [63245]
    SCr less than 0.5 mg/dL: 15 mg/kg/dose IV every 12 hours.
    SCr 0.5 to 0.7 mg/dL: 20 mg/kg/dose IV every 24 hours.
    SCr 0.8 to 1 mg/dL: 15 mg/kg/dose IV every 24 hours.
    SCr 1.1 to 1.4 mg/dL: 10 mg/kg/dose IV every 24 hours.
    SCr more than 1.4 mg/dL: 15 mg/kg/dose IV every 48 hours.
     
    Intermittent hemodialysis
    For IV dosing, maintaining predialysis serum vancomycin concentrations between 15 and 20 mg/L is likely to attain the AUC target of 400 to 600 mg x hour/L in the previous 24 hours with higher AUC/MIC values occurring on days prior. Predialysis serum concentration monitoring should be performed at least weekly and should drive subsequent dosing. Loading and maintenance doses should be based on the timing of the dose and dialyzer permeability. Vancomycin dosing data are limited in pediatric patients receiving hemodialysis; therefore, recommendations are based on guideline recommendations for adult patients.[65262]
     
    Adult and Pediatric patients - dosing after dialysis ends† [65262]
    Low permeability dialyzer: 25 mg/kg/dose (actual body weight) IV loading dose; 7.5 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
    High permeability dialyzer: 25 mg/kg/dose (actual body weight) IV loading dose; 10 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
     
    Adult and Pediatric patients - intradialytic dosing† [65262]
    Low permeability dialyzer: 30 mg/kg/dose (actual body weight) IV loading dose; 7.5 to 10 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
    High permeability dialyzer: 35 mg/kg/dose (actual body weight) IV loading dose; 10 to 15 mg/kg/dose (actual body weight) IV maintenance dose (generally 3 times per week).
     
    Peritoneal dialysis†
    Adult and Pediatric patients
    Serum concentrations above 15 mcg/mL are recommended when administered intraperitoneally. Clearance of vancomycin by intermittent peritoneal dialysis is highly variable.[53190] [61676]
     
    Continuous renal replacement therapy (CRRT)†
    NOTE: Various CRRT modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), continuous venovenous hemodiafiltration (CVVHDF), continuous venovenous high-flux hemodialysis (CVVHFD), continuous arteriovenous hemofiltration (CAVH), continuous arteriovenous hemodialysis (CAVHD), and continuous arteriovenous hemodiafiltration (CAVHDF). Dosing should take into consideration patient-specific factors (e.g. intrinsic renal function), type of infection, the duration of renal replacement therapy, the effluent flow rate, and the replacement solution administered.[42303] For CRRT operating in an uninterrupted fashion, vancomycin clearance is relatively constant over the dosing interval, although clearance may decline as the hemodiafilter clogs over time. Vancomycin clearance is related closely to the rate of ultrafiltrate/dialysate flow.[65262] Definitive dosage recommendations have not been established in pediatric patients; therefore, recommendations are based on guideline recommendations for adult patients.[24879] [41118] [41119] [41120] [42303]
     
    Adult and Pediatric patients
    Loading doses of 20 to 25 mg/kg/dose (actual body weight) IV should be used in patients receiving CRRT at conventional, KDIGO-recommended effluent rates of 20 to 25 mL/kg/h. Initial maintenance doses with these effluent rates should be 7.5 to 10 mg/kg/dose (actual body weight) IV every 12 hours. Further maintenance dosing should be based on serum concentration monitoring conducted within the first 24 hours. In fluid overloaded patients, doses may be reduced as patients become euvolemic and drug Vd decreases. Continuous infusion vancomycin may be considered in these patients, especially when high CRRT ultrafiltrate/dialysate flow rates are employed.[65262]
     
    Hybrid hemodialysis†
    NOTE: Hybrid treatments include prolonged intermittent renal replacement therapy (PIRRT), sustained low-efficiency dialysis (SLED), slow extended daily dialysis/diafiltration (SLEDD-f), and extended daily dialysis (EDD). Dosing should take into consideration patient-specific factors (e.g. intrinsic renal function), the type of infection, the duration of renal replacement therapy, the ultrafiltration rate, the dialysis flow rate, and how often dialysis sessions occur.[65397]
     
    Adult and Pediatric patients
    NOTE: Vancomycin dosing data are limited in pediatric patients receiving hybrid hemodialysis; therefore, recommendations are based on guideline recommendations for adult patients.[65262]
     
    Loading doses of 20 to 25 mg/kg/dose (actual body weight) IV and initial doses should not be delayed until the end of the dialysis session. Maintenance doses of 15 mg/kg/dose (actual body weight) IV should be administered after the dialysis session ends or during the final 60 to 90 minutes of dialysis. Concentration monitoring should guide further maintenance doses. Serum concentrations obtained 2 hours after the vancomycin infusion and immediately prior to PIRRT can be used to calculate the AUC for dosing modifications.[65262]

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    May be administered with or without food. Swallow whole; do not crush or chew.

    Oral Liquid Formulations

    Powder for oral solution
    Shake well before each administration.
    Measure dosage with a calibrated spoon, cup, or oral syringe.[62844]
     
    Reconstitution
    Available as a compounding kit containing 1 bottle of vancomycin powder and 1 bottle of grape-flavored diluent.
    Various bottle sizes are available, which, when reconstituted, produce either a 25 or 50 mg/mL vancomycin oral solution. Select the appropriate bottle size/concentration for the individual patient.
    Remove the cap from the bottle containing the vancomycin powder. Tap the top of the induction seal to loosen the powder. Slowly peel back the foil seal.
    Shake the bottle containing grape-flavored diluent for a few seconds before removing the cap.
    Open the diluent bottle and empty about half of the contents into the vancomycin powder bottle.
    Replace the cap and shake the mixture vertically for approximately 45 seconds.
    Add the remaining diluent into the vancomycin powder bottle.
    Replace the cap and shake the bottle for approximately 30 seconds.
    Storage: Store under refrigeration at 2 to 8 degrees C (36 to 46 degrees F); do not freeze. Discard any unused solution after 14 days. Keep container tightly closed and protect from light.[62844]

    Extemporaneous Compounding-Oral

    If a commercial oral product is not available, vancomycin powder for injection (not including ADD-Vantage vials) may be used for enteral administration. Dilute the appropriate dose in 1 ounce of water. Common flavoring syrups may be added to the solution to improve palatability. Prepare the solution just before administration. Administer orally or via a nasogastric tube.[40937]

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Intermittent Intravenous (IV) Infusion
    Powder vials for injection
    Reconstitution
    Reconstitute vials with Sterile Water for Injection to yield a 50 mg/mL solution.
    Reconstitute the 250 mg vial with 5 mL of Sterile Water for Injection.
    Reconstitute the 500 mg vial with 10 mL of Sterile Water for Injection.
    Reconstitute the 750 mg vial with 15 mL of Sterile Water for Injection.
    Reconstitute the 1,000 mg vial with 20 mL of Sterile Water for Injection.
    Reconstitute the 1,250 mg vial with 25 mL of Sterile Water for Injection.
    Reconstitute the 1,500 mg vial with 30 mL of Sterile Water for Injection.
    FURTHER DILUTION IS REQUIRED BEFORE ADMINISTRATION.
    Storage: Reconstituted vials may be stored in the refrigerator for up to 14 days.[40937] [63969]
     
    Dilution
    Further dilute the reconstituted solution with a compatible IV solution to a final concentration of 5 mg/mL.
    Dilute the 250 mg reconstituted vial with 50 mL of infusion solution.
    Dilute the 500 mg reconstituted vial with 100 mL of infusion solution.
    Dilute the 750 mg reconstituted vial with 150 mL of infusion solution.
    Dilute the 1,000 mg reconstituted vial with 200 mL of infusion solution.
    Dilute the 1,250 mg reconstituted vial with 250 mL of infusion solution.
    Dilute the 1,500 mg reconstituted vial with 300 mL of infusion solution.
    A final concentration of 5 mg/mL is recommended for administration; however, a concentration of up to 10 mg/mL may be used in patients in need of fluid restriction. Higher concentrations may increase the risk of infusion-related reactions.[40937] [63969]
    Institute for Safe Medication Practices (ISMP)/Vermont Oxford Network (VON) Recommended Standard Concentration for Neonatal Administration: 5 mg/mL [51889]
    Storage: Solutions diluted with 5% Dextrose Injection or 0.9% Sodium Chloride Injection may be stored in the refrigerator for up to 14 days. Solutions diluted with 5% Dextrose Injection and 0.9% Sodium Chloride Injection, Lactated Ringer's Injection, Lactated Ringer's and 5% Dextrose Injection, Normosol-M and 5% Dextrose Injection, or Isolyte E may be stored in the refrigerator for up to 96 hours.[40937] [63969]
     
    Bulk vials for injection
    Reconstitution
    Reconstitute vials with Sterile Water for Injection.
    Reconstitute the 5 g vial with 100 mL of Sterile Water for Injection to yield a 500 mg/10 mL (50 mg/mL) solution.
    Reconstitute the 10 g vial with 95 mL of Sterile Water for Injection to yield a 500 mg/5 mL (100 mg/mL) solution.
    Penetrate the bulk vial once with a suitable sterile dispensing set that allows measured distribution of the contents. Use the entire contents of the bulk vial during reconstitution.
    FURTHER DILUTION IS REQUIRED BEFORE ADMINISTRATION.
    Storage: Once penetration of the bulk vial has occurred with the sterile dispensing set, withdraw contents promptly. A maximum of 4 hours from initial penetration may be allowed to complete fluid aliquoting/transferring operations before discarding the container.[40953] [40955]
     
    Dilution
    Further dilute the reconstituted solution with a compatible IV solution to a final concentration of 5 mg/mL. Concentrations of up to 10 mg/mL may be used in patients in need of fluid restriction; higher concentrations may increase the risk of infusion-related reactions.
    Institute for Safe Medication Practices (ISMP)/Vermont Oxford Network (VON) Recommended Standard Concentration for Neonatal Administration: 5 mg/mL [51889]
    Compatible fluids include 5% Dextrose Injection, 0.9% Sodium Chloride Injection, 5% Dextrose Injection and 0.9% Sodium Chloride Injection, Lactated Ringer's Injection, Lactated Ringer's and 5% Dextrose Injection, Normosol-M and 5% Dextrose Injection, or Isolyte E.
    Storage: Specific storage instructions after dilution are not provided in the FDA-approved labeling for bulk products. Use compounded admixtures as soon as feasible.[40953] [40955] Product labeling for the vancomycin 1 g vials product states that solutions diluted in 5% Dextrose Injection or 0.9% Sodium Chloride Injection are stable for 96 hours under refrigeration.[40937]
     
    ADD-Vantage IV solution
    Reconstitution
    Reconstitute only with 0.9% Sodium Chloride Injection or 5% Dextrose Injection in the appropriate flexible diluent container provided. For 500 mg vials, use at least a 100 mL diluent container and for 750 mg and 1 g vials, use only the 250 mL diluent container.
    Remove the protective covers from the top of the vial and vial port. Remove vial cap (do not access with a syringe) and vial port cover. Screw the vial into the vial port until it will go no further to assure a seal. Once vial is sealed to the port, do not remove. To activate the contents of the vial, squeeze the bottom of the diluent container gently to inflate the portion of the container surrounding the end of the drug vial. With the other hand, push the drug vial down into the container telescoping walls of the container and grasp the inner cap of the vial through the walls of the container. Pull the inner cap from the drug vial. Verify the rubber stopper has been pulled out, allowing the drug and diluent to mix. Mix the container contents thoroughly.
    Storage: The admixture solution may be stored for up to 24 hours at room temperature or in the refrigerator for up to 14 days.
    Do not use in series connections with flexible containers.[40957]
     
    Pre-mixed Galaxy IV solution
    Preparation
    Thaw frozen containers at room temperature (25 degrees C or 77 degrees F) or under refrigeration (5 degrees C or 41 degrees F). Do not force thaw by immersion in water baths or by microwave irradiation. Check for leaks by squeezing bag firmly.
    Do not add supplementary medication.
    Contents of the solution may precipitate in the frozen state and should dissolve with little or no agitation once the solution has reached room temperature.
    Storage: The thawed solution is stable for 72 hours at room temperature or 30 days under refrigeration. Do not refreeze thawed product.
    Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.[40956]
     
    Flexible bag IV solution
    Preparation
    Remove the flexible bag from the aluminum overpouch. Check for leaks by squeezing bag firmly.
    Do not add supplementary medication.
    Storage: The solution is stable for 28 days at room temperature (up to 25 degrees C or 77 degrees F) after removal from the aluminum overpouch.
    Do not use flexible bags in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.[63968]
     
    Intermittent IV infusion
    Infuse over at least 1 hour to reduce the risk of infusion-related reactions. Larger loading doses may require extended infusion times (at least 2 to 3 hours).
    Infusion rates of 10 to 15 mg/minute are recommended.[40937] [40953] [40955] [40957] [65262]
     
    Plasmapheresis
    Administer dose after plasmapheresis.[33359]
     
    Continuous Intravenous (IV) Infusion†
    NOTE: Vancomycin is not FDA-approved to be administered by continuous IV infusion.
    Reconstitution
    Reconstitution for continuous infusion is not specifically discussed in the literature. Follow manufacturer instructions.[40937] [40953] [40955] [63969]
     
    Dilution
    A study in 12 adults used 1 or 2 g of vancomycin diluted in 1,000 mL of 0.9% Sodium Chloride Injection and infused over 24 hours. Doses were reconstituted less than 12 hours before infusion and refrigerated at 4 degrees C until administration.[40974]
    A study in 10 adults used 2 g of vancomycin diluted in 250 mL of 5% Dextrose Injection and infused over 24 hours.[40975]
    A study in 75 adults used 15 to 60 mg/kg/day, rounded to the nearest 250 mg dose, diluted in 500 mL of unspecified fluid and infused over 24 hours.[65316]
    A study in 94 adults used 10 g of vancomycin diluted in 1,000 mL of 5% Dextrose Injection and infused over 24 to 48 hours.[65317] [65320]
    A study in 60 adults used 40 to 60 mg/kg/day of vancomycin diluted in 50 mL of 5% Dextrose Injection and infused over 12 hours twice daily.[65318]
    A study in 76 adults used 1 g of vancomycin diluted in 50 mL of unspecified fluid and infused 2 g at a rate of 4.2 mL/hour, 1 g at a rate of 2.1 mL/hour, and 500 mg at a rate of 1 mL/hour.[65319]
    Stability:
    A study used 10 g of vancomycin diluted in 1,000 mL of 5% Dextrose Injection.[65320]
    Doses were stored at 4 degrees C until approximately 15 minutes before use. Doses were infused at room temperature for 24 to 48 hours. The concentration of vancomycin in the remaining fluid of the infusion sets was approximately equivalent to the inital concentration (10 g/L).
    Additionally, samples of concentrated solutions (up to 83 g/L) were incubated at increasing temperatures up to 50 degrees C for up to 72 hours. Samples degraded less than 5% when kept for 72 hours at up to 37 degrees C. Samples exposed to 50 degrees C showed more than 7% degradation.
     
    Continuous IV infusion
    Continuous infusion regimens usually start after an initial loading dose.[65262]
    Doses have been administered over 12 to 48 hours.[40974] [40975] [65316] [65317] [65318] [65319] [65320]
     
    Intravenous (IV) Vancomycin Desensitization†
    NOTE: Vancomycin is not FDA-approved for desensitization.
    NOTE: Once the desensitization process is complete, do not miss scheduled vancomycin doses to avoid drug-free periods, or the desensitization process will have to be repeated. Desensitization is required before any subsequent vancomycin use in hypersensitive patients as desensitization does not extend beyond the time frame that vancomycin has been stopped.[27463]
    NOTE: Concomitant use of medications that may induce histamine response may lead to unsuccessful desensitization, and the use of these medications should be temporarily withheld, changed to an alternative, or given in restricted amounts. Medications that are potential histamine inducers included ciprofloxacin, barbiturates, opioids (fentanyl rarely induces histamine), neuromuscular antagonists (succinylcholine and benzylisoquinolinium compounds, not steroidal compounds), propofol, plasma expanders (dextran, polygeline), and radiocontrast agents.[27463]
     
    Preparation and administration of infusions for rapid vancomycin desensitization (Lerner and Dwyer protocol) [27461]
    Dilution
    Prepare the standard solution by diluting 500 mg vancomycin in 250 mL of 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Label as "Infusion 5: vancomycin 2 mg/mL".
    Draw 10 mL of the standard vancomycin 2 mg/mL solution and place in 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Label as "Infusion 4: vancomycin 0.2 mg/mL".
    Draw 10 mL of the vancomycin 0.2 mg/mL solution and place in 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Label as "Infusion 3: vancomycin 0.02 mg/mL".
    Draw 10 mL of the vancomycin 0.02 mg/mL solution and place in 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Label as "Infusion 2: vancomycin 0.002 mg/mL".
    Draw 10 mL of the standard vancomycin 0.002 mg/mL solution and place in 100 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection.
    Label as "Infusion 1: vancomycin 0.0002 mg/mL".
     
    Intermittent IV infusion
    Give diphenhydramine and a corticosteroid 15 minutes before initiating the protocol, then every 6 hours throughout the protocol.
    Administer the 5 infusions in succession at an initial rate of 30 mL/hour and increase by 30 mL/hour as tolerated every 5 minutes up to a maximum rate of 300 mL/hour.
    If pruritus, hypotension, rash, or difficulty breathing occurs, stop the infusion and reinfuse the previously tolerated infusion at the highest tolerated rate. This step may be repeated up to 3 times for any given concentration.
    Upon completion of Infusion 5, immediately administer the required dose of vancomycin over 2 hours. Decrease rate if the patient becomes symptomatic, or alternatively, increase rate if the patient tolerates dose.
    Administer diphenhydramine 60 minutes before each subsequent dose.
     
    Preparation and administration of infusions for slow vancomycin desensitization (Lin protocol) [27462]
    Dilution
    Day 1: 0.5 mg in 500 mL 0.9% Sodium Chloride Injection (0.001 mg/mL) IV infusion.
    Day 2: 5 mg in 500 mL 0.9% Sodium Chloride Injection (0.01 mg/mL) IV infusion.
    Day 3: 50 mg in 500 mL 0.9% Sodium Chloride Injection (0.1 mg/mL) IV infusion.
    Day 4: 50 mg in 500 mL 0.9% Sodium Chloride Injection (0.1 mg/mL) IV infusion.
    Day 5: 250 mg in 500 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection (0.5 mg/mL) IV infusion.
    Day 6: 500 mg in 500 mL 0.9% Sodium Chloride Injection or 5% Dextrose Injection (1 mg/mL) IV.
     
    Intermittent IV infusion
    Concurrently start diphenhydramine and an H2-blocker with the first vancomycin dose, and continue at regular dosing intervals throughout the desensitization protocol.
    Administer 1 infusion on 6 consecutive days at a rate of 100 mL/hour.
    Administer the required vancomycin dose on day 7. Consider discontinuation of diphenhydramine and the H2-blocker.

    Other Injectable Administration

    Intraventricular Administration†
    NOTE: Vancomycin is not FDA-approved for intraventricular administration.
    Use preservative-free product.[61814]
    Concentrations of 10 mg in 1 to 10 mL of 0.9% Sodium Chloride Injection have been used.[65335] [65336]
    Reports describe varying amounts of CSF aspirated into the syringe containing the vancomycin dose for instillation and potentially followed by a 2 mL flush of 0.9% Sodium Chloride Injection.[65334] [65335] [65337]
    When administered through a ventricular drain, the drain should be clamped for 15 to 60 minutes to allow the antimicrobial solution to equilibrate in the CSF before opening the drain.[61814]

    Rectal Administration
    Extemporaneous Compounding-Rectal

    Retention Enema (using powder for injection)
    Doses of 500 mg to 1 g diluted in volumes of 100 to 500 mL of 0.9% Sodium Chloride Injection have been utilized.[56690] [56692] [56693] [62877]
    While no specific dilution instructions have been described, preparation of the enema per the instructions associated with each specific powder for injection product would seem warranted.
    Stability should coincide with specific powder for injection product labeling.[40937] [40953] [40955] [63969]
     
    Instillation
    While guidelines do not provide specific instillation recommendations, a method of instilling the dose over 15 minutes with clamping of the tube for 1 to 2 hours has been described.[56692] Specific patient circumstances will likely dictate the duration of the dwell.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Discard unused product 28 days after first opening the pouch
    - Store below 77 degrees F
    - Store in original container
    First-Vancomycin:
    - After compounding, store product in the refrigerator (between 36 to 46 degrees F)
    - Prior to compounding, store at room temperature (between 59 to 86 degrees F)
    - Protect from freezing
    - Protect from light
    FIRVANQ:
    - Discard any unused reconstituted product after 14 days
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from freezing
    - Protect from light
    - Store between 36 to 46 degrees F
    Vancocin:
    - Discard unused portion 4 hours after initial entry of container
    - Store in original container
    - Store unreconstituted product at 68 to 77 degrees F
    VANCOSOL:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Corn hypersensitivity, vancomycin hypersensitivity

    Vancomycin is contraindicated in patients who have a history of vancomycin hypersensitivity. Vancomycin solutions containing dextrose may be contraindicated in patients with history of corn hypersensitivity or corn product hypersensitivity.

    Viral infection

    This drug does not treat viral infection (e.g., common cold). Prescribing vancomycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria. Patients should be told to complete the full course of treatment, even if they feel better earlier.

    Nephrotoxicity, renal disease, renal failure, renal impairment

    Vancomycin should be used with caution in patients with renal impairment because it can accumulate. Doses should be adjusted in patients with renal dysfunction. Vancomycin serum concentrations and renal-function tests should be performed during therapy, especially when concurrent nephrotoxic agents, such as aminoglycosides, are used. Nephrotoxicity (renal failure), principally manifested by azotemia (increased BUN) or increased serum creatinine, has been rarely reported with vancomycin. The risk for nephrotoxicity is increased in patients receiving large doses of vancomycin, in those receiving other nephrotoxic drugs such as aminoglycosides, or those who had preexisting renal disease or impairment. Historically, nephrotoxicity may be associated with product impurity. As monotherapy, nephrotoxicity associated with vancomycin in the literature is reported to be 5 to 7% or less. Vancomycin does potentiate the nephrotoxic effects of aminoglycosides and may increase that potential by 3- to 4-fold. Vancomycin exposure to renal proximal tubule epithelial cells results in increased oxygen consumption and ATP concentrations. Toxicity is not limited to the proximal tubules, but may also involve the medullary regions (loop of Henle and collecting duct) of the nephron. Vancomycin toxicity resulting in the destruction of glomeruli and proximal tubule necrosis may be due to oxidative stress. Nephrotoxicity due to vancomycin monotherapy is usually reversible. Higher doses have been associated with nephrotoxicity in some studies; however, concomitant nephrotoxic agents, severity of illness, patient hemodynamics, and the use of pressors may all complicate the interpretation of nephrotoxicity in these patients. Additionally, it is often difficult to determine if higher vancomycin concentrations preceded nephrotoxicity or were a result of worsening renal impairment.

    Extravasation, infusion-related reactions, intracameral administration, intramuscular administration, intrathecal administration, intravitreal administration, ocular surgery

    Administer each intravenous vancomycin dose over at least 60 minutes. Larger loading doses may require extended infusion times of at least 2 to 3 hours. Infusion rates of 10 to 15 mg/minute are recommended. Too-rapid administration can lead to infusion-related reactions such as 'red man syndrome'. The frequency of infusion-related events may be higher with the concomitant administration of anesthetic agents. In addition, care must be taken to avoid extravasation because vancomycin is extremely irritating to tissues. Avoid intramuscular administration due to severe pain at the injection site. The safety and efficacy of intrathecal administration (intralumbar or intraventricular), intraperitoneal administration, intracameral administration, or intravitreal administration have not been established. Intraperitoneal administration of vancomycin has been associated with peritonitis. Hemorrhagic occlusive retinal vasculitis (HORV), including permanent loss of vision, has occurred in patients receiving intracameral or intravitreal administration of vancomycin during or after cataract surgery (ocular surgery).[40955] [40956] [62413] [65262]

    Hearing impairment, ototoxicity, tinnitus

    Vancomycin administration is associated with a risk for ototoxicity. Vancomycin should be used with caution in patients with underlying hearing impairment or tinnitus. The manufacturer recommends serial auditory function tests while patients receive vancomycin. Ototoxicity (hearing impairment or loss) has been reported with vancomycin therapy and may be transient or permanent. Factors that may increase the risk of developing ototoxicity include: excessive dose, underlying hearing loss, renal dysfunction, or multiple ototoxic drugs. The true incidence of ototoxicity is controversial. Early studies indicate a range of 1% to 9%; however, this rate may be inflated due to impurities associated with older formulations. The risk of ototoxicity from vancomycin monotherapy is low (without concurrent ototoxic agents). Severe ototoxicity is characterized by auditory nerve damage that initially affects high-frequency sensory hairs in the cochlea and then middle- and low-frequency hairs that can lead to total hearing loss. High-tone deafness occurs before low-tone deafness and is permanent. Reversible ototoxicity, such as tinnitus, can occur with or without high-tone deafness. Early studies attributed hearing loss to high vancomycin concentrations, but subsequent data suggest that there may be a lack of correlation between serum concentrations and ototoxicity.

    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 vancomycin, 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.

    Neonates, premature neonates

    The clearance of vancomycin in neonates decreases as postconceptional age decreases, therefore, longer dosing intervals may be necessary in premature neonates.

    Pregnancy

    There are no available data on vancomycin use in pregnant women to assess a risk of major birth defects or miscarriage. Available published data on intravenous vancomycin use in pregnancy during the second and third trimesters have not shown an association with adverse maternal or fetal outcomes.[28468] [63969] The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low.[27016] [33052] Certain formulations of injectable vancomycin contain excipients, such as polyethylene glycol (PEG) 400 and N-acetyl-D-alanine (NADA), which have caused fetal malformations in animal reproductive studies. If vancomycin use is needed during pregnancy, utilize other available formulations.[63968] Systemic absorption of vancomycin is low after oral administration; however, absorption may vary depending on various factors.[28468] [63969] Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood concentrations in 1 newborn were about 76% of the mother's serum concentrations after the mother received vancomycin 1 g IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted.[33051] Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 g IV every 12 hours for at least 1 week.[33052] In a study evaluating hearing loss and nephrotoxicity in infants of 10 pregnant women treated with IV vancomycin in the second or third trimester, no infant had abnormal sensorineural hearing at 3 months or nephrotoxicity. In a study of 55 pregnant women who received IV vancomycin at the time of delivery, no major adverse reactions were noted in the newborns or the mothers, including no sensorineural hearing loss. Neonatal renal function was not examined.[28468] [63969] Animal data do not demonstrate any risk of teratogenic or toxic effects on the fetus.[28468] [33050] [33054] [28468] [33053]

    Breast-feeding

    There is insufficient data on the presence of vancomycin in human milk. There are no data on the effects of vancomycin on the breast-fed infant or milk production. Systemic absorption of vancomycin is low after oral administration; therefore, it is unlikely to result in clinically relevant exposure in nursing infants.[28468] [62844] [63969] In 1 woman treated with intravenous vancomycin 1 g every 12 hours, a single breast-milk concentration of 12.7 mcg/mL was measured at 4 hours after infusion. Her peak and trough serum vancomycin concentrations were 36.1 mcg/mL and12.5 mcg/mL, respectively.[33052] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for vancomycin and any potential adverse effects on the breast-fed infant from vancomycin or the underlying maternal condition.[28468] [62844] [63969]

    Geriatric

    Geriatric patients may need monitoring and/or initial dosage adjustments because of a higher risk of toxicity and drug accumulation secondary to age-related decrease in renal function. Clinical studies with oral vancomycin demonstrated that geriatric patients are at an increased risk of nephrotoxicity during or after completion of therapy for pseudomembranous colitis. Additionally, patients older than 65 years of age may take longer to respond to therapy for Clostridium difficile; therefore, it is important for clinicians to be aware of the appropriate duration of therapy to avoid discontinuation or switching to alternative therapy prematurely. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral vancomycin must be accompanied by monitoring of renal function tests, including a baseline value, and serum vancomycin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. 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.

    Heart failure, sodium restriction

    Due to the sodium content, avoid certain vancomycin products in patients with heart failure, requiring sodium restriction, and the elderly. Consult specific product labeling for precise sodium content.

    Serious rash

    Serious rash events, including toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome (SJS), drug reaction with eosinophilia and systemic symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and linear IgA bullous dermatosis (LABD), have been reported with vancomycin therapy. Cutaneous signs or symptoms reported include skin rash, mucosal lesions, and blisters. Discontinue vancomycin at the first appearance of signs and symptoms of severe skin reaction.

    ADVERSE REACTIONS

    Severe

    renal failure (unspecified) / Delayed / 0-7.0
    hearing loss / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    interstitial nephritis / Delayed / Incidence not known
    cardiac arrest / Early / Incidence not known
    vasculitis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    exfoliative dermatitis / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
    C. difficile-associated diarrhea / Delayed / Incidence not known
    hemorrhagic occlusive retinal vasculitis / Delayed / Incidence not known
    visual impairment / Early / Incidence not known

    Moderate

    hypokalemia / Delayed / 13.0-13.0
    neutropenia / Delayed / 2.0-12.0
    peripheral edema / Delayed / 6.0-6.0
    vancomycin infusion reaction / Rapid / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    hypotension / Rapid / Incidence not known
    dyspnea / Early / Incidence not known
    erythema / Early / Incidence not known
    phlebitis / Rapid / Incidence not known
    wheezing / Rapid / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    constipation / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    depression / Delayed / Incidence not known

    Mild

    nausea / Early / 17.0-17.0
    abdominal pain / Early / 15.0-15.0
    fever / Early / 9.0-9.0
    diarrhea / Early / 9.0-9.0
    vomiting / Early / 9.0-9.0
    flatulence / Early / 8.0-8.0
    infection / Delayed / 8.0-8.0
    headache / Early / 7.0-7.0
    back pain / Delayed / 6.0-6.0
    fatigue / Early / 5.0-5.0
    tinnitus / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    dizziness / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    flushing / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    paresthesias / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    rash / Early / Incidence not known
    chills / Rapid / Incidence not known
    insomnia / Early / Incidence not known

    DRUG INTERACTIONS

    Acyclovir: (Moderate) Closely monitor renal function if concomitant use with acyclovir and vancomycin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
    Adefovir: (Moderate) Adefovir is eliminated renally by a combination of glomerular filtration and active tubular secretion; coadministration of adefovir dipivoxil with drugs that reduce renal function or compete for active tubular secretion, such as parenteral vancomycin, may decrease adefovir elimination by competing for common renal tubular transport systems, thereby increasing serum concentrations of adefovir and/or vancomycin. Additionally, chronic coadministration of adefovir with nephrotoxic drugs, such as vancomycin, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Aldesleukin, IL-2: (Moderate) Aldesleukin may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects with Aldesleukin, such as vancomycin, may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
    Alfentanil: (Moderate) The concurrent administration of vancomycin and anesthetics, like alfentanil, has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Amikacin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Aminoglycosides: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Amlodipine; Celecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as Amphotericin B, can lead to additive nephrotoxicity. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as vancomycin, as the risk of renal impairment may be increased.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Azelastine; Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bacitracin: (Moderate) Additive nephrotoxicity may occur with concurrent use of systemic bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations if these drugs must be used together.
    Beclomethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Benzonatate: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Beractant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants, such as beractant should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
    Betamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bleomycin: (Minor) Previous treatment with nephrotoxic agents, like vancomycin, may result in decreased bleomycin clearance if renal function has been impaired. Monitor for signs/symptoms of bleomycin toxicity in patients with concomittant or prior vancomycin therapy.
    Budesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Budesonide; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Budesonide; Glycopyrrolate; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bupivacaine; Meloxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Calfactant: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
    Capreomycin: (Major) Since capreomycin is eliminated by the kidney, coadministration of with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. Theoretically, the chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered.
    Celecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Cholestyramine: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 to 6 hours after cholestyramine (or as great an interval as possible). Cholestyramine can bind other drugs, such as oral vancomycin, when given concurrently.
    Ciclesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cidofovir: (Contraindicated) The administration of cidofovir other potentially nephrotoxic agents, such as IV vancomycin, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Cisplatin: (Moderate) Closely monitor renal function and audiometric testing if concomitant use with cisplatin and vancomycin is necessary. Both cisplatin and vancomycin can cause nephrotoxicity and ototoxicity, which may be additive when used together.
    Clindamycin: (Moderate) Concomitant use of vancomycin and clindamycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Colesevelam: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 4 hours before colesevelam. Colesevelam can bind other drugs, such as oral vancomycin, when given concurrently.
    Colestipol: (Major) The concurrent use of anion-exchange resins and oral vancomycin is contraindicated by clinical practice guidelines. Per FDA-approved labeling, administer other drugs at least 1 hour before or 4 hours after colestipol (or as great an interval as possible). Colestipol can bind other drugs, such as oral vancomycin, when given concurrently.
    Colistimethate, Colistin, Polymyxin E: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered.
    Colistin: (Major) Since colistimethate sodium is eliminated by the kidney, coadministration with other potentially nephrotoxic drugs, including vancomycin, may increase serum concentrations of either drug. The chronic coadministration of these drugs may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs must be coadministered.
    Corticosteroids: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cyclosporine: (Minor) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as vancomycin. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including vancomycin, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
    Deflazacort: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    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.
    Dexamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Diclofenac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Diclofenac; Misoprostol: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    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.
    Diflunisal: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Diphenhydramine; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Diphenhydramine; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Donepezil; Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate.
    Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    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.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    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.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Entecavir: (Moderate) Vancomycin and entecavir both undergo renal tubular secretion. Monitor patients closely for adverse events when these drugs are coadministered. Elevated serum concentrations of either drug may occur.
    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.
    Ethacrynic Acid: (Major) Vancomycin should be used cautiously with other ototoxic drugs such as ethacrynic acid.
    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.
    Etodolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    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.
    Famotidine; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Fenoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Fentanyl: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions. Infusion-related events may be minimized by the administration of vancomycin as a 60-minute infusion prior to anesthetic induction.
    Fludrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Flunisolide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Flurbiprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Salmeterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Formoterol; Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as parenteral vancomycin. Nephrotoxicity is also possible in patients receiving oral vancomycin for pseudomembranous colitis, should systemic absorption occur through significantly altered GI mucosa. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Furosemide: (Moderate) Vancomycin should be used cautiously with other ototoxic drugs such as furosemide.
    Gallium Ga 68 Dotatate: (Major) Avoid use of mannitol and vancomycin, if possible. Concomitant administration of nephrotoxic drugs, such as vancomycin, increases the risk of renal failure after administration of mannitol.
    Gallium: (Contraindicated) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as vancomycin, may increase the risk for developing severe renal insufficiency. If use of vancomycin is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of vancomycin is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with ganciclovir should be done cautiously to avoid additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    General anesthetics: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Gentamicin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Gold: (Minor) Both vancomycin and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Hydrocodone; Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Hydrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like vancomycin may increase the risk of developing nephrotoxicity.
    Ibuprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Ibuprofen; Oxycodone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Ibuprofen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune Globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like vancomycin. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Also, closely monitor renal function.
    Indomethacin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Inotersen: (Moderate) Use caution with concomitant use of inotersen and vancomycin due to the risk of glomerulonephritis and nephrotoxicity.
    Kanamycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Ketoprofen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Ketorolac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Lansoprazole; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    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.
    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.
    Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
    Lorazepam: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Mannitol: (Major) Avoid use of mannitol and vancomycin, if possible. Concomitant administration of nephrotoxic drugs, such as vancomycin, increases the risk of renal failure after administration of mannitol.
    Meclofenamate Sodium: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Mefenamic Acid: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Meloxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Memantine: (Moderate) Cationic drugs that are eliminated by renal tubular secretion, such as vancomycin, may compete with memantine for common renal tubular transport systems, thus possibly decreasing the elimination of one of the drugs. Although theoretical, careful patient monitoring of response to memantine and/or vancomycin is recommended to assess for needed dosage adjustments. In selected individuals, vancomycin serum concentration monitoring may be appropriate.
    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.
    Methohexital: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Methotrexate: (Major) Avoid concomitant use of methotrexate with vancomycin due to the risk of additive nephrotoxicity as well as an increased risk of severe methotrexate-related adverse reactions. Recent exposure to vancomycin, in the absence of overt renal impairment, may also adversely affect methotrexate excretion and increase risk of toxicity. If concomitant use is unavoidable, closely monitor for adverse reactions. Vancomycin and methotrexate are both nephrotoxic drugs; methotrexate is also renally eliminated. Coadministration of methotrexate with vancomycin may result in decreased renal function as well as increased methotrexate plasma concentrations. In a case report, two patients who had received a methotrexate-containing chemotherapy regimen initially displayed appropriate methotrexate clearance. However, administration of vancomycin in between chemotherapy treatment cycles appears to have caused markedly prolonged methotrexate clearance (i.e., 170 to 231 hours to reach serum methotrexate concentrations of less than 0.2 micro-M). Subclinical renal impairment was documented in both cases following vancomycin administration, which eventually resolved; subsequent methotrexate cycles, of the same dose, showed appropriate clearance.
    Methylprednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Nabumetone: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Naproxen; Esomeprazole: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Naproxen; Pseudoephedrine: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nonsteroidal antiinflammatory drugs: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    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.
    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.
    Oxaliplatin: (Major) Avoid coadministration of oxaliplatin with vancomycin due to the risk of increased oxaliplatin-related adverse reactions. Vancomycin is known to be potentially nephrotoxic; because platinum-containing drugs like oxaliplatin are eliminated primarily through the kidney, oxaliplatin clearance may be decreased by coadministration with nephrotoxic agents.
    Oxaprozin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, like vancomycin, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Paromomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Pentamidine: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as systemic pentamidine, can lead to additive nephrotoxicity. Renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations.
    Piperacillin: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended.
    Piperacillin; Tazobactam: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended.
    Piroxicam: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Plazomicin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Polymyxin B: (Major) Systemic polymyxin B should not be used concurrently or sequentially with other drugs that have the potential for nephrotoxicity or neurotoxicity such as vancomycin. Topical products containing polymyxin B, especially when they are applied over a large body surface area, should be used cautiously with any of the above drugs. If concurrent systemic use is necessary, renal function should be monitored closely and vancomycin doses should be adjusted according to vancomycin serum concentrations. Diminishing urine output and a rising BUN are indications to discontinue systemic polymyxin B therapy.
    Poractant Alfa: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.
    Prednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Prednisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    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: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rofecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents, such as vancomycin, may lead to additive nephrotoxicity.
    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.
    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.
    Streptomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Streptozocin: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drug, such as streptozocin, can lead to additive nephrotoxicity.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sufentanil: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Sulindac: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Sumatriptan; Naproxen: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Tacrolimus: (Moderate) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as tacrolimus, can lead to additive nephrotoxicity. Monitor renal function closely and adjust vancomycin or tacrolimus doses according to serum concentrations.
    Telbivudine: (Moderate) Drugs that alter renal function such as vancomycin may alter telbivudine plasma concentrations because telbivudine is eliminated primarily by renal excretion. Monitor renal function before and during telbivudine treatment.
    Tenofovir Alafenamide: (Moderate) Tenofovir-containing products should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: (Moderate) Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent, such as vancomycin. Patients receiving these drugs together should be carefully monitored for changes in serum creatinine and phosphorus. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir; a majority of cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents.
    Thiopental: (Moderate) The concurrent administration of vancomycin and anesthetics has been associated with erythema, histamine-like flushing, and anaphylactoid reactions.
    Tobramycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Tolmetin: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
    Triamcinolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Trospium: (Moderate) Both trospium and vancomycin are eliminated by active renal tubular secretion; coadministration has the potential to increase serum concentrations of trospium or vancomycin due to competition for the drug elimination pathway. Careful patient monitoring and dosage adjustment of trospium and/or vancomycin is recommended.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Valacyclovir: (Moderate) Closely monitor renal function if concomitant use with valacyclovir and vancomycin is necessary. Both drugs can cause nephrotoxicity, which may be additive when used together.
    Valdecoxib: (Minor) It is possible that additive nephrotoxicity may occur in patients who receive NSAIDs concurrently with other nephrotoxic agents, including vancomycin.
    Valganciclovir: (Moderate) Concurrent use of nephrotoxic agents, such as vancomycin, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and vancomycin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Voclosporin: (Moderate) Concomitant use of voclosporin and vancomycin may result in additive nephrotoxicity. Monitor for renal toxicity if concomitant use is required.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zoledronic Acid: (Moderate) Coadministration of zoledronic acid with other potentially nephrotoxic drugs, such as vancomycin, may increase serum concentrations of either drug and increase the risk of nephrotoxicity. Monitor patients for changes in renal function if these drugs are coadministered.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on vancomycin use in pregnant women to assess a risk of major birth defects or miscarriage. Available published data on intravenous vancomycin use in pregnancy during the second and third trimesters have not shown an association with adverse maternal or fetal outcomes.[28468] [63969] The fetal risk of ototoxic and/or nephrotoxic effects from vancomycin when administered during pregnancy is considered to be low.[27016] [33052] Certain formulations of injectable vancomycin contain excipients, such as polyethylene glycol (PEG) 400 and N-acetyl-D-alanine (NADA), which have caused fetal malformations in animal reproductive studies. If vancomycin use is needed during pregnancy, utilize other available formulations.[63968] Systemic absorption of vancomycin is low after oral administration; however, absorption may vary depending on various factors.[28468] [63969] Vancomycin crosses the placenta and can accumulate in amniotic fluid. Cord blood concentrations in 1 newborn were about 76% of the mother's serum concentrations after the mother received vancomycin 1 g IV every 12 hours for 13 days; no maternal nephrotoxicity or ototoxicity was noted.[33051] Congenital abnormalities were not noted in newborns of mothers who received vancomycin 1 g IV every 12 hours for at least 1 week.[33052] In a study evaluating hearing loss and nephrotoxicity in infants of 10 pregnant women treated with IV vancomycin in the second or third trimester, no infant had abnormal sensorineural hearing at 3 months or nephrotoxicity. In a study of 55 pregnant women who received IV vancomycin at the time of delivery, no major adverse reactions were noted in the newborns or the mothers, including no sensorineural hearing loss. Neonatal renal function was not examined.[28468] [63969] Animal data do not demonstrate any risk of teratogenic or toxic effects on the fetus.[28468] [33050] [33054] [28468] [33053]

    There is insufficient data on the presence of vancomycin in human milk. There are no data on the effects of vancomycin on the breast-fed infant or milk production. Systemic absorption of vancomycin is low after oral administration; therefore, it is unlikely to result in clinically relevant exposure in nursing infants.[28468] [62844] [63969] In 1 woman treated with intravenous vancomycin 1 g every 12 hours, a single breast-milk concentration of 12.7 mcg/mL was measured at 4 hours after infusion. Her peak and trough serum vancomycin concentrations were 36.1 mcg/mL and12.5 mcg/mL, respectively.[33052] Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for vancomycin and any potential adverse effects on the breast-fed infant from vancomycin or the underlying maternal condition.[28468] [62844] [63969]

    MECHANISM OF ACTION

    Vancomycin is bactericidal and appears to exert its effect by binding to the precursor units of bacterial cell walls, inhibiting their synthesis. It specifically binds with the D-alanyl-D-alanine terminus of the peptide precursor units, inhibiting peptidoglycan polymerase and transpeptidation reactions. This prevents cross-linking of the cell wall peptidoglycan during the second stage of cell synthesis. The net result is an alteration of bacterial cell wall permeability and cell death. In addition, RNA synthesis is inhibited. Vancomycin is not active in vitro to gram-negative organisms, mycobacteria, of fungi.[34153] [40937] [40938]
     
    Vancomycin exhibits 'concentration-independent killing' in which there is saturation of the bacterial killing rate once the drug concentrations approach the minimum inhibitory concentration (MIC).[34142] [34143] [34144] [34145] Time-kill studies showed little difference in concentrations from 2 to 40 times the MIC.[34146] A study evaluating the area-under-the-curve and MIC (AUC:MIC), also known as area-under-the-inhibitory curve (AUIC), in an attempt to define efficacy parameters, showed patients with an AUC:MIC of less than 125 had a higher probability of failure (p = 0.004).[34155] A study in pneumonia patients specifically evaluating the relationship of AUC:MIC and vancomycin suggests there is a significant relationship between AUC:MIC and efficacy of vancomycin. Patients in this study with treatment cures averaged an AUC:MIC of 491 as compared to an average AUC:MIC of 306 for treatment failures. Since vancomycin has relatively poor penetration into respiratory secretions, this could account for the higher AUC:MIC necessary for success in this study.[34147] Guidelines suggest that an AUC:MIC ratio of 400 or more is necessary to achieve clinical effectiveness with vancomycin.[35013] As AUC:MIC appears to be the major pharmacodynamic predictor for vancomycin, total antibiotic exposure is the key to a successful vancomycin regimen.
     
    Most strains of S. aureus, S. epidermidis, Streptococcus sp., and Corynebacterium sp. are susceptible to vancomycin. Vancomycin is particularly useful against penicillin- and methicillin-resistant staphylococcal infections and for treating other gram-positive infections in beta-lactam-allergic patients. However, there are a few case reports of S. aureus strains that are insensitive to vancomycin.[34148] While, traditionally, vancomycin has been used to treat enterococcal infections, there is a significant resistance rate in these organisms. Vancomycin-resistant enterococci (VRE) rates up to 12.1% have been reported in bloodstream isolates and up to 25% of ICU enterococcal infections.[34149] [34150] Synergistic bactericidal effects can be achieved when vancomycin is combined with aminoglycosides against gram-positive organisms, but this increases possible toxicity. Vancomycin is useful against a wide variety of clinical infections due to these pathogens. When given orally, vancomycin is also useful in treating C. difficile.[62844]
     
    The susceptibility interpretive criteria for vancomycin are delineated by pathogen. The MICs are defined for S. aureus as susceptible at 2 mcg/mL or less, intermediate at 4 to 8 mcg/mL, and resistant at 16 mcg/mL or more. The MICs are defined for Enterococcus sp. and Staphylococcus sp. other than S. aureus as susceptible at 4 mcg/mL or less, intermediate at 8 to 16 mcg/mL, and resistant at 32 mcg/mL or more.[63320] [63321] However, reports suggest that S. aureus isolates with vancomycin MICs of 1 to 2 mcg/mL may be less likely to be successfully treated with vancomycin.[35013] The MICs are defined for beta-hemolytic Streptococcus sp., viridans group Streptococcus sp., and S. pneumoniae as susceptible at 1 mcg/mL or less.[63320] [63321]
     
    While vancomycin has been a predominant agent to treat gram-positive infections, increasing resistance has started to limit its utility. Vancomycin-resistant enterococci (VRE) is the most common resistant pathogen. There are 6 types of reported vancomycin resistance in enterococci (VanA, VanB, VanC, VanD, VanE, and VanG). Of these, 5 types are acquired resistance, while VanC is an intrinsic resistance found in E. gallinarum and E. casseliflavus. The most common type is VanA resistance. Once exposed to an inducer, like vancomycin, transcription of the enzymes that make the cell-wall precursors is altered. There is an increase in the cell-wall precursors ending in D-alanyl-D-lactate, to which vancomycin has a low binding affinity, and a decrease in the D-alanyl-D-alanine cell-wall precursors, to which vancomycin has a high binding affinity. This results in decreased binding of vancomycin to the receptor sites of the enterococcal cell wall. The genes for this resistance can potentially be spread to other bacteria via plasmids. Exposure to IV and oral vancomycin, antianaerobic antibiotics, and other broad-spectrum antibiotics have all been associated as factors contributing to VRE.[34152] [34153] S. aureus is another concerning organism with increasing resistance to vancomycin. Strains of vancomycin-intermediate S. aureus (VISA), heterogeneous vancomycin-intermediate S. aureus (hVISA), and vancomycin-resistance S. aureus (VRSA) have been described in the literature. Strains of VISA have shown an unusually thickened cell wall that prevents drug penetration. The cell wall also contains dipeptides that bind vancomycin. Fully resistant strains, VRSA, have acquired VanA resistance similar to Enterococcus sp.[34153] [34154] Guidelines suggest that exposure to vancomycin trough serum concentrations of less than 10 mg/L may produce S. aureus strains with VISA-like characteristics.[35013]

    PHARMACOKINETICS

    In general, vancomycin is only administered intravenously although oral administration is important in the treatment of some GI infections such as pseudomembranous colitis. Vancomycin is not administered intramuscularly due to severe pain at the injection site.
     
    Systemically administered vancomycin is distributed into most body tissues and fluids including pericardial fluid, pleural fluid, ascitic fluid, synovial fluid, urine, peritoneal dialysis fluid, and atrial appendage tissue. Concentrations obtained in tissues and fluids are variable and somewhat dependent on the degree of inflammation present. The volume of distribution coefficient is reported by the manufacturer as 0.3 to 0.43 L/kg; however, literature reports give a range of 0.2 to 1.9 L/kg. Unless the meninges are inflamed, there is little diffusion into CSF (0 to 3.45 mg/L) with corresponding CSF:serum ratios of 0 to 0.18. Inflamed meninges improve penetration into the CSF with reported concentrations of 6.4 to 11.1 mg/L with corresponding CSF:serum ratio of 0.36 to 0.46. Vancomycin is about 55% (range: 44% to 82%) bound to serum protein in healthy volunteers with normal renal function. There is no apparent metabolism of vancomycin. Excretion is mainly by glomerular filtration, with about 80% of the drug excreted in 24 hours in the urine and only small amounts excreted in the feces. In patients with normal renal function, vancomycin has a serum half-life of about 4 to 6 hours. Mean plasma clearance is approximately 0.058 L/kg/hour and mean renal clearance is approximately 0.048 L/kg/hour.

    Oral Route

    Oral bioavailability of vancomycin is too low to treat systemic infections; serum concentrations are often undetectable even when inflammatory lesions are present. Patients with pseudomembranous colitis, however, may develop detectable serum levels following oral administration, especially if they have renal impairment. Due to poor oral bioavailability, oral doses of vancomycin are excreted mainly in the feces (exceeding 100 mg/kg) with urinary recovery not exceeding 0.76% of the dose.

    Intravenous Route

    According to the manufacturer, after intravenous administration of 1,000 mg (15 mg/kg) over 1 hour, vancomycin plasma concentrations reach a peak of approximately 63 mcg/mL and fall to about 23 mcg/mL 2 hours after infusion, and 8 mcg/mL 11 hours after the end of the infusion. Multiple doses of 500 mg infused over 30 minutes produces mean serum concentrations of approximately 49 mcg/mL at the end of the infusion, 19 mcg/mL 2 hours after the infusion, and 10 mcg/mL 6 hours after the infusion. Vancomycin serum concentrations are highly variable and depend on many patient factors including age, size, fluid status, infection source/type, and renal function. Serum concentrations should be monitored individually to determine effective dosing.

    Other Route(s)

    Peritoneal Route
    According to the manufacturer, approximately 60% of an intraperitoneal vancomycin dose, administered via intraperitoneal injection, is absorbed systemically in 6 hours. Serum concentrations of approximately 10 mcg/mL are achieved by an intraperitoneal dose of 30 mg/kg.
     
    Rectal Route (Retention Enema)
    Similar to oral administration, patients with pseudomembranous colitis may develop detectable serum levels after rectal administration of retention enemas. Patients with renal impairment may be at a higher risk of systemic absorption.