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  • metronidazole - Drug Summary

  • CLASSES

    Agents for Amoebiasis and Other Protozoal Diseases
    Anaerobicides
    Gynecological Antibiotics and Sulfonamides
    Imidazole Derivative Antibiotics
    Topical Antiinfectives for Acne
    Topical Rosacea Agents

    BOXED WARNING

    New primary malignancy

    Metronidazole, when given systemically, has been reported to be carcinogenic in mice and rats. Similar studies in the hamster gave negative results. Also, metronidazole has shown mutagenic activity in a number of in vitro assay systems, but studies in mammals (in vivo) failed to demonstrate a potential for genetic damage. Human data are not available to describe the risk of a new primary malignancy secondary to use. The boxed warning states that systemic metronidazole use should be reserved for conditions where the drug is clearly needed; avoid unnecessary use. Vaginal and topical forms of metronidazole do not carry the boxed warning regarding carcinogenicity.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral/parenteral/topical/vaginal synthetic nitroimidazole; antibacterial and antiprotozoal
    Used for anaerobic bacterial infections and protozoal infections such as trichomoniasis, amebiasis, and giardiasis
    Associated with neurotoxicity

    COMMON BRAND NAMES

    Flagyl, Flagyl ER, Flagyl RTU, MetroCream, MetroGel, MetroGel Vaginal, MetroGel-Vaginal, MetroLotion, Noritate, NUVESSA, Nydamax, Rosadan, Vandazole, Vitazol

    HOW SUPPLIED

    Flagyl ER Oral Tab ER: 750mg
    Flagyl RTU/Metronidazole Intravenous Inj Sol: 1mL, 5mg
    Flagyl/Metronidazole Oral Cap: 375mg
    Flagyl/Metronidazole Oral Tab: 250mg, 500mg
    MetroCream/Metronidazole/Noritate/Rosadan/Vitazol Topical Cream: 0.75%, 1%
    MetroGel/MetroGel Vaginal/MetroGel-Vaginal/Metronidazole/NUVESSA/Vandazole Vaginal Gel: 0.75%, 1.3%
    MetroGel/Metronidazole/Nydamax/Rosadan Topical Gel: 0.75%, 1%
    MetroLotion/Metronidazole Topical Lotion: 0.75%

    DOSAGE & INDICATIONS

    For the treatment of trichomoniasis.
    For the initial treatment of trichomoniasis.
    Oral dosage (immediate-release)
    Adult Females

    500 mg PO twice daily for 7 days. Sexual partners should be referred and evaluated for appropriate treatment. The FDA-approved dosage is: 2 g PO as a single dose or 1 g PO twice daily for 1 day or 250 mg PO 3 times daily or 375 mg PO twice daily for 7 days.

    Adult Males

    2 g PO as a single dose. Sexual partners should be referred and evaluated for appropriate treatment. The FDA-approved dosage is: 2 g PO as a single dose or 1 g PO twice daily for 1 day or 250 mg PO 3 times daily or 375 mg PO twice daily for 7 days.

    Female Children weighing 45 kg or more† and Adolescents†

    500 mg PO twice daily for 7 days. Sexual partners should be referred and evaluated for appropriate treatment.

    Male Children weighing 45 kg or more† and Adolescents†

    2 g PO as a single dose. Sexual partners should be referred and evaluated for appropriate treatment.

    Children weighing less than 45 kg†

    45 mg/kg/day PO in 3 divided doses for 7 days.

    For the treatment of recurrent or resistant trichomoniasis.
    Oral dosage (immediate-release)
    Adult Females

    500 mg PO twice daily for 7 days if treatment failure occurs with reexposure. If treatment failure occurs with no reexposure, treat with 2 g PO once daily for 7 days. Sexual partners should be referred and evaluated for appropriate treatment.

    Adult Males

    2 g PO as a single dose if treatment failure occurs with reexposure. If treatment failure occurs with no reexposure, treat with 500 mg PO twice daily for 7 days. Treatment with 2 g PO once daily for 7 days can be considered for resistant infections. Sexual partners should be referred and evaluated for appropriate treatment.

    Female Children weighing 45 kg or more† and Adolescents†

    500 mg PO twice daily for 7 days if treatment failure occurs with reexposure. If treatment failure occurs with no reexposure, treat with 2 g PO once daily for 7 days. Sexual partners should be referred and evaluated for appropriate treatment.

    Male Children weighing 45 kg or more† and Adolescents†

    2 g PO as a single dose if treatment failure occurs with reexposure. If treatment failure occurs with no reexposure, treat with 500 mg PO twice daily for 7 days. Treatment with 2 g PO once daily for 7 days can be considered for resistant infections. Sexual partners should be referred and evaluated for appropriate treatment.

    For the treatment of bacterial vaginosis.
    Vaginal dosage (0.75% gel)
    Adults

    1 applicatorful (5 g of 0.75% metronidazole gel) intravaginally once daily for 5 days. The FDA-approved dosage is 1 applicatorful intravaginally 1 to 2 times daily for 5 days, depending on the product used. For once daily dosing, administer at bedtime. In patients with multiple recurrences, metronidazole gel administered twice weekly for more than 3 months has been shown to reduce recurrences, but the benefit may not persist when therapy is stopped. Limited data suggest that an oral nitroimidazole followed by intravaginal boric acid with suppressive metronidazole gel for 4 to 6 months may be an option for recurrent bacterial vaginosis.

    Adolescents (post-menarchal)

    1 applicatorful (5 g of 0.75% metronidazole gel) intravaginally once daily for 5 days; administer at bedtime. In patients with multiple recurrences, metronidazole gel administered twice weekly for more than 3 months has been shown to reduce recurrences, but the benefit may not persist when therapy is stopped. Limited data suggest that an oral nitroimidazole followed by intravaginal boric acid with suppressive metronidazole gel for 4 to 6 months may be an option for recurrent bacterial vaginosis.

    Vaginal dosage (1.3% gel)
    Adults

    1 applicatorful (5 g of 1.3% gel containing 65 mg of metronidazole) intravaginally as a single dose at bedtime as an alternative.

    Children and Adolescents 12 to 17 years

    1 applicatorful (5 g of 1.3% gel containing 65 mg of metronidazole) intravaginally as a single dose at bedtime as an alternative.

    Oral dosage (immediate-release)†
    Adults

    500 mg PO twice daily for 7 days. For patients with multiple recurrences, limited data suggest that an oral nitroimidazole, such as metronidazole 500 mg PO twice daily for 7 days, followed by intravaginal boric acid with suppressive metronidazole gel may be an option. Monthly oral metronidazole 2 g PO with fluconazole has been evaluated as suppressive therapy.

    Children weighing 45 kg or more and Adolescents

    500 mg PO twice daily for 7 days. For patients with multiple recurrences, limited data suggest that an oral nitroimidazole, such as metronidazole 500 mg PO twice daily for 7 days, followed by intravaginal boric acid with suppressive metronidazole gel may be an option. Monthly oral metronidazole 2 g PO with fluconazole has been evaluated as suppressive therapy.

    Infants and Children weighing less than 45 kg

    15 to 25 mg/kg/day PO in 3 divided doses for 7 days.

    Oral dosage (extended-release)
    Adults

    750 mg PO once daily for 7 days.

    For the treatment of gynecologic infections, including endometritis, endomyometritis, post-surgical cuff infection, pelvic inflammatory disease (PID), and tubo-ovarian abscess.
    For the treatment of mild-to-moderate PID.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily in combination with doxycycline for 14 days and either single dose ceftriaxone IM, cefoxitin IM plus probenecid, or other parenteral third generation cephalosporin. For patients with cephalosporin allergy, if the community prevalence and individual risk of gonorrhea are low, and if follow-up is assured, metronidazole in combination with a fluoroquinolone (levofloxacin, moxifloxacin) or azithromycin for 14 days may be considered. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.

    Adolescents†

    500 mg PO twice daily in combination with doxycycline for 14 days and either single dose ceftriaxone IM, cefoxitin IM plus probenecid, or other parenteral third generation cephalosporin. For patients with cephalosporin allergy, if the community prevalence and individual risk of gonorrhea are low, and if follow-up is assured, metronidazole in combination with a fluoroquinolone (levofloxacin, moxifloxacin) or azithromycin for 14 days may be considered. Patients who fail to respond within 72 hours should be reevaluated to confirm diagnosis and switched to IV therapy.

    For the treatment of unspecified gynecologic infections, including endometritis and endomyometritis.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 to 12 hours. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 7 to 10 days.

    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours. The FDA-approved dosage is 15 mg/kg IV loading dose, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours for 7 to 10 days.

    For the treatment of severe PID or tubo-ovarian abscess.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily in combination with doxycycline as part of initial treatment with ceftriaxone and as stepdown from IV treatment for a total of 14 days of therapy.

    Adolescents†

    500 mg PO twice daily in combination with doxycycline as part of initial treatment with ceftriaxone and as stepdown from IV treatment for a total of 14 days of therapy.

    Intravenous dosage
    Adults

    500 mg IV twice daily in combination with doxycycline and ceftriaxone. IV therapy should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral metronidazole and doxycycline for a total of 14 days of therapy.

    Adolescents†

    500 mg IV twice daily in combination with doxycycline and ceftriaxone. IV therapy should be continued for at least 24 to 48 hours after clinical improvement, and then stepdown to oral metronidazole and doxycycline for a total of 14 days of therapy.

    For the treatment of postpartum endometritis.
    Intravenous dosage
    Adults

    500 mg IV every 8 hours in combination with ampicillin and gentamicin. Continue treatment until clinical improvement and afebrile for 24 to 48 hours.

    For the treatment of acute intestinal amebiasis (amebic dysentery) and disseminated amebiasis, including hepatic abscess.
    For the treatment of mild to moderate intestinal amebiasis (amebic dysentery).
    Oral dosage (immediate-release)
    Adults

    500 to 750 mg PO every 8 hours for 5 to 10 days followed by either iodoquinol or paromomycin.

    Infants, Children, and Adolescents

    30 to 50 mg/kg/day PO divided every 8 hours (Max: 750 mg/dose) for 5 to 10 days followed by either iodoquinol or paromomycin.

    For the treatment of severe intestinal amebiasis (amebic dysentery) or disseminated amebiasis, including hepatic abscess.
    Oral dosage (immediate-release)
    Adults

    500 to 750 mg PO every 8 hours for 5 to 10 days followed by either iodoquinol or paromomycin.

    Infants, Children, and Adolescents

    30 to 50 mg/kg/day PO divided every 8 hours (Max: 750 mg/dose) for 5 to 10 days followed by either iodoquinol or paromomycin.

    Intravenous dosage†
    Adults

    750 mg IV every 8 hours for 5 to 10 days followed by either iodoquinol or paromomycin.

    Infants, Children, and Adolescents

    30 to 50 mg/kg/day IV divided every 8 hours (Max: 750 mg/dose) for 5 to 10 days followed by either iodoquinol or paromomycin.

    For the treatment of central nervous system infections, including meningitis and brain abscess.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 6 to 8 hours. Optimal treatment duration is not well-defined and will depend on causative pathogen and clinical course; treatment durations of 1 to 6 weeks for meningitis and 4 to 6 weeks for brain abscess have been reported in small studies and case reports. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours. Optimal treatment duration is not well-defined and will depend on causative pathogen and clinical course; treatment durations of 1 to 6 weeks for meningitis and 4 to 6 weeks for brain abscess have been reported in small studies and case reports. 

    Neonates older than 40 weeks postmenstrual age†

    10 mg/kg/dose PO every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose PO every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    7.5 mg/kg/dose PO every 12 hours.

    Intravenous dosage
    Adults

    500 mg IV every 6 to 8 hours. Optimal treatment duration is not well-defined and will depend on causative pathogen and clinical course; treatment durations of 1 to 6 weeks for meningitis and 4 to 6 weeks for brain abscess have been reported in small studies and case reports. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours. Optimal treatment duration is not well-defined and will depend on causative pathogen and clinical course; treatment durations of 1 to 6 weeks for meningitis and 4 to 6 weeks for brain abscess have been reported in small studies and case reports. 

    Neonates older than 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.

    For the treatment of acne rosacea.
    Topical dosage (0.75% Gel, Cream, or Lotion)
    Adults

    Apply thin film of 0.75% metronidazole topical cream, gel, or lotion to the cleansed, affected areas twice daily in the morning and evening. Once response occurs, adjust frequency and duration of therapy according to severity of disease.

    Topical dosage (1% Gel or Cream)
    Adults

    Apply and rub in a thin film of 1% metronidazole gel or cream once daily to the cleansed, affected area(s).

    For the treatment of lower respiratory tract infections, including pleural empyema, pneumonia, and lung abscess.
    For the treatment of pneumonia and lung abscess.
    Oral dosage
    Adults

    500 mg PO every 8 to 12 hours. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    10 mg/kg/dose PO every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose PO every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    7.5 mg/kg/dose PO every 12 hours.

    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.

    For the treatment of empyema.
    Oral dosage
    Adults

    500 mg PO every 8 to 12 hours. Use metronidazole in combination with a second- or third-generation cephalosporin for community-acquired empyema or with vancomycin and cefepime for hospital-acquired or postprocedural empyema. Treat for a minimum of 2 weeks after drainage and defervescence. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days. 

    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours. Use metronidazole in combination with a second- or third-generation cephalosporin for community-acquired empyema or with vancomycin and cefepime for hospital-acquired or postprocedural empyema. Treat for a minimum of 2 weeks after drainage and defervescence. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    For the treatment of skin and skin structure infections, including cellulitis, erysipelas, necrotizing infections, animal bite wounds, leg ulcer, diabetic foot ulcer, and surgical incision site infections.
    For the treatment of surgical incision site infections.
    Intravenous dosage
    Adults

    500 mg IV every 8 hours plus ceftriaxone, ciprofloxacin, or levofloxacin for incisional surgical site infections of the intestinal or genitourinary tract or axilla or perineum.

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

    500 mg IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus cefotaxime, aminoglycoside, or quinolone for mixed necrotizing infections.

    Infants†, Children†, and Adolescents†

    7.5 mg/kg/dose (Max: 500 mg/dose) IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus cefotaxime or aminoglycoside for mixed necrotizing infections.

    Neonates older than 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus cefotaxime or aminoglycoside for mixed necrotizing infections.

    Neonates 35 to 40 weeks postmenstrual age†

    15 mg/kg IV once, then 7.5 mg/kg/dose IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus cefotaxime or aminoglycoside for mixed necrotizing infections.

    Neonates 34 weeks postmenstrual age and younger†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus cefotaxime or aminoglycoside for mixed necrotizing infections.

    For the treatment of animal bite wounds.
    Oral dosage (immediate-release)
    Adults

    250 to 500 mg PO every 8 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

    Intravenous dosage
    Adults

    500 mg IV every 8 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

    For the treatment of unspecified skin and skin structure infections.
    Oral dosage (immediate-release)
    Adults

    7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    10 mg/kg/dose PO every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose PO every 8 hours.

    Neonates 34 weeks postmenstrual age and younger

    7.5 mg/kg/dose PO every 12 hours.

    Intravenous dosage
    Adults

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.

    For the treatment of leg ulcer.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 hours for 7 days plus sulfamethoxazole; trimethoprim or ceftriaxone.

    Intravenous dosage
    Adults

    500 mg IV every 8 hours for 7 days plus sulfamethoxazole; trimethoprim or ceftriaxone.

    For the treatment of diabetic foot ulcer.
    Intravenous dosage
    Adults

    500 mg IV every 6 hours for 7 to 14 days for moderate or severe infections including ischemic limb/necrosis/gas forming. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

    For the treatment of cellulitis or erysipelas.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 hours for 5 to 14 days plus clarithromycin as an alternative for infections near the eyes or nose.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 5 to 14 days plus clarithromycin as an alternative for infections near the eyes or nose.

    Intravenous dosage
    Adults

    500 mg IV every 8 hours for 5 to 14 days plus clarithromycin as an alternative for infections near the eyes or nose.

    Infants†, Children†, and Adolescents†

    22.5 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours for 5 to 14 days plus clarithromycin as an alternative for infections near the eyes or nose.

    For the treatment of endocarditis.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 to 12 hours. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    For the treatment of bone and joint infections, including osteomyelitis and infectious arthritis.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 to 12 hours for 4 to 6 weeks. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours for 4 to 6 weeks. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    For bacterial vaginosis prophylaxis† or trichomoniasis prophylaxis† in victims of sexual assault.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily for 7 days.

    Adolescents

    500 mg PO twice daily for 7 days.

    For the treatment of recurrent and persistent non-gonococcal urethritis (NGU)†.
    Oral dosage (immediate-release)
    Adults

    2 g PO as a single dose for males who have sex with females in areas where T. vaginalis is prevalent.

    For the treatment of dental infection† or dentoalveolar infection†, including periodontitis†.
    Oral dosage (immediate-release)
    Adults

    250 mg PO 3 or 4 times daily for 10 days or 500 mg PO 3 times daily for 8 days has been recommended. For severe periodontitis, 250 mg PO 3 times daily with amoxicillin for 7 to 10 days has been used. For refractory disease in patients with beta-lactam allergy, 500 mg PO twice daily with ciprofloxacin for 8 days.

    Adolescents 16 years and older

    250 mg PO 3 or 4 times daily for 10 days or 500 mg PO 3 times daily for 8 days has been recommended. For severe periodontitis, 250 mg PO 3 times daily with amoxicillin for 7 to 10 days has been used.

    For surgical infection prophylaxis, including bowel preparation† in patients undergoing colorectal surgery.
    For bowel preparation in patients undergoing colorectal surgery†.
    Oral dosage (immediate-release)
    Adults

    1 g PO in combination with neomycin for 3 doses given over 10 hours beginning the afternoon and evening prior to the surgery. Intravenous antibmicrobial prophylaxis should also be given prior to the surgical incision.

    Infants, Children, and Adolescents

    15 mg/kg/dose (Max: 1 g/dose) PO in combination with neomycin for 3 doses given over 10 hours beginning the afternoon and evening prior to the surgery. Intravenous antibmicrobial prophylaxis should also be given prior to the surgical incision.

    For general surgical infection prophylaxis.
    Intravenous dosage
    Adults

    500 mg IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. May continue 500 mg IV every 6 hours for no more than 24 hours post-operatively if necessary.[36054] [53477] The FDA-approved dose is 15 mg/kg/dose IV as a single dose within 60 minutes prior to the surgical incision, then 7.5 mg/kg/dose IV every 6 hours for 2 doses. Metronidazole is FDA-approved for elective, contaminated or potentially contaminated colorectal surgery.[36894] Guidelines recommend metronidazole in combination with cefazolin for uncomplicated appendectomy, obstructed small intestine, and clean-contaminated head and neck or urologic procedures or in combination with cefazolin or ceftriaxone for colorectal procedures.[53477] Metronidazole is also recommended in combination with an aminoglycoside or fluoroquinolone as alternate therapy in patients with beta-lactam allergy for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, hysterectomy, or clean-contaminated urologic procedures.[36054] [53477]

    Infants†, Children†, and Adolescents†

    15 mg/kg/dose (Max: 500 mg/dose) IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. May continue 15 mg/kg/dose (Max: 500 mg/dose) IV every 8 hours for no more than 24 hours post-operatively if necessary.[53477] Guidelines recommend metronidazole in combination with cefazolin for uncomplicated appendectomy, obstructed small intestine, and clean-contaminated head and neck or urologic procedures or in combination with cefazolin or ceftriaxone for colorectal procedures. Metronidazole is also recommended in combination with an aminoglycoside or fluoroquinolone as alternate therapy in patients with beta-lactam allergy for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, or clean-contaminated urologic procedures.[53477]

    Neonates weighing 1.2 kg or more†

    15 mg/kg/dose IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. A duration of prophylaxis less than 24 hours for most procedures is recommended. Guidelines recommend metronidazole in combination with cefazolin for uncomplicated appendectomy, obstructed small intestine, and clean-contaminated head and neck or urologic procedures or in combination with cefazolin or ceftriaxone for colorectal procedures. Metronidazole is also recommended in combination with an aminoglycoside or fluoroquinolone as alternate therapy in patients with beta-lactam allergy for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, or clean-contaminated urologic procedures.

    Premature Neonates weighing less than 1.2 kg†

    7.5 mg/kg/dose IV as a single dose within 60 minutes prior to the surgical incision; no intraoperative redosing is necessary. A duration of prophylaxis less than 24 hours for most procedures is recommended. Guidelines recommend metronidazole in combination with cefazolin for uncomplicated appendectomy, obstructed small intestine, and clean-contaminated head and neck or urologic procedures or in combination with cefazolin or ceftriaxone for colorectal procedures. Metronidazole is also recommended in combination with an aminoglycoside or fluoroquinolone as alternate therapy in patients with beta-lactam allergy for biliary tract, uncomplicated appendectomy, obstructed small intestine, colorectal, or clean-contaminated urologic procedures.

    For surgical infection prophylaxis for induced abortion/dilation and evacuation procedures†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily for 5 days.

    For the treatment of pseudomembranous colitis† due to C. difficile infection†.
    For the treatment of non-severe initial episode of pseudomembranous colitis† due to C. difficile infection†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 times daily for 10 days as an alternative.

    Infants, Children, and Adolescents

    7.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 to 8 hours for 10 days as first-line therapy.

    For the treatment of fulminant initial episode of pseudomembranous colitis† due to C. difficile infection†.
    Intravenous dosage
    Adults

    500 mg IV every 8 hours plus vancomycin.

    Infants, Children, and Adolescents

    7.5 mg/kg/dose (Max: 500 mg/dose) IV every 6 to 8 hours for 10 days plus vancomycin.

    For the treatment of non-severe first recurrence of pseudomembranous colitis† due to C. difficile infection†.
    Oral dosage (immediate-release)
    Infants, Children, and Adolescents

    7.5 mg/kg/dose (Max: 500 mg/dose) PO every 6 to 8 hours for 10 days as first-line therapy.

    For the treatment of pseudomembranous colitis† due to C. difficile infection† when no oral treatment is possible.
    Intravenous dosage
    Adults

    500 mg IV every 8 hours plus rectal vancomycin.

    For the treatment of Crohn's disease† associated with colonic and/or perianal involvement.
    Oral dosage (immediate-release)
    Adults

    1,000 to 1,500 mg/day PO in 2 to 4 divided doses. In some patients, higher doses (up to 20 mg/kg/day) may be needed for the treatment of perianal disease. Guidelines state that metronidazole may be effective and strongly recommends consideration in treating simple perianal fistulas.

    Children and Adolescents

    15 to 20 mg/kg/day PO in 2 to 3 divided doses based on limited data in pediatric patients. In adult studies of patients with Crohn's disease, usual doses have ranged from 1,000 to 1,500 mg/day in 2 to 4 divided doses. Metronidazole, in combination with ciprofloxacin or azithromycin, has been shown to improve the clinical symptoms of Crohn's disease and may be effective in inducing remission in patients with active Crohn's disease.

    For Helicobacter pylori (H. pylori) eradication†.
    As part of clarithromycin-based initial therapy in adults with or without potential macrolide exposure or resistance.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily as part of a combination therapy as a first-line treatment option. Quadruple therapy includes metronidazole in combination with clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) for 10 to 14 days. Hybrid therapy includes amoxicillin plus a PPI for 7 days followed by metronidazole in combination with clarithromycin, amoxicillin, and a PPI for 7 days. Sequential therapy may begin after 5 to 7 days of amoxicillin and a PPI as metronidazole in combination with clarithromycin and a PPI for 5 to 7 days.

    As part of clarithromycin-based initial therapy in adults without previous macrolide exposure in regions where clarithromycin resistance is less than 15%.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 times daily in combination with clarithromycin and a proton pump inhibitor for 14 days as a first-line treatment option.

    In combination with amoxicillin and a proton pump inhibitor (PPI) in pediatric patients.
    Oral dosage (immediate-release)
    Children and Adolescents weighing 35 kg or more

    500 mg PO twice daily in combination with amoxicillin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    Children and Adolescents weighing 25 to 34 kg

    500 mg PO in the morning and 250 mg PO in the evening (tablets) OR 375 mg PO twice daily (oral suspension) in combination with amoxicillin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    Children weighing 15 to 24 kg

    250 mg PO twice daily in combination with amoxicillin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with standard-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with known susceptibility to metronidazole and resistance to clarithromycin. Triple therapy with high-dose amoxicillin, metronidazole, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    As part of a sequential therapy regimen in pediatric patients.
    Oral dosage (immediate-release)
    Children and Adolescents weighing 35 kg or more

    500 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 5 days, after initial therapy with amoxicillin and a PPI for 5 days. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.

    Children and Adolescents weighing 25 to 34 kg

    500 mg PO in the morning and 250 mg PO in the evening (tablets) OR 375 mg PO twice daily (oral suspension) in combination with clarithromycin and a proton pump inhibitor (PPI) for 5 days, after initial therapy with amoxicillin and a PPI for 5 days. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.

    Children weighing 15 to 24 kg

    250 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 5 days, after initial therapy with amoxicillin and a PPI for 5 days. Sequential therapy is a first-line treatment option for patients infected with fully susceptible H. pylori strains. Sequential therapy is not recommended if susceptibility testing is unavailable.

    In combination with clarithromycin and a proton pump inhibitor (PPI) for penicillin-allergic pediatric patients.
    Oral dosage (immediate-release)
    Children and Adolescents weighing 35 kg or more

    500 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with metronidazole, clarithromycin, and a PPI is recommended for penicillin-allergic patients infected with fully susceptible H. pylori strains.[63135]

    Children and Adolescents weighing 25 to 34 kg

    500 mg PO in the morning and 250 mg PO in the evening (tablets) OR 375 mg PO twice daily (oral suspension) in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with metronidazole, clarithromycin, and a PPI is recommended for penicillin-allergic patients infected with fully susceptible H. pylori strains.

    Children weighing 15 to 24 kg

    250 mg PO twice daily in combination with clarithromycin and a proton pump inhibitor (PPI) for 14 days. Triple therapy with metronidazole, clarithromycin, and a PPI is recommended for penicillin-allergic patients infected with fully susceptible H. pylori strains.

    As part of a quadruple therapy regimen in pediatric patients.
    Oral dosage (immediate-release)
    Children and Adolescents weighing 35 kg or more

    500 mg PO twice daily in combination with amoxicillin, clarithromycin, and a proton pump inhibitor (PPI) for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    Children and Adolescents weighing 25 to 34 kg

    500 mg PO in the morning and 250 mg PO in the evening (tablets) OR 375 mg PO twice daily (oral suspension) in combination with amoxicillin, clarithromycin, and a proton pump inhibitor (PPI) for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    Children weighing 15 to 24 kg

    250 mg PO twice daily in combination with amoxicillin, clarithromycin, and a proton pump inhibitor (PPI) for 14 days. Concomitant quadruple therapy with amoxicillin, metronidazole, clarithromycin, and a PPI is a first-line treatment option for patients infected with H. pylori strains with dual resistance to clarithromycin and metronidazole or strains with unknown susceptibility.

    As part of clarithromycin-based salvage therapy in adults who failed initial bismuth quadruple therapy.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 2 or 3 times daily in combination with clarithromycin, amoxicillin, and a proton pump inhibitor (PPI) for 10 to 14 days. For patients with a penicillin allergy, metronidazole is recommended in combination with clarithromycin and a PPI for 14 days.

    As part of levofloxacin-based initial therapy in adults.
    Oral dosage (immediate-release)
    Adults

    500 mg PO twice daily in combination with levofloxacin and a proton pump inhibitor (PPI) for 5 to 7 days after amoxicillin in combination with a PPI for 5 to 7 days. Guidelines recommend this sequential therapy as a first-line treatment option.

    As part of bismuth quadruple initial therapy in adults.
    Oral dosage (immediate-release)
    Adults

    250 mg PO 4 times daily or 500 mg PO 3 or 4 times daily in combination with bismuth subcitrate or subsalicylate, tetracycline, and a proton pump inhibitor for 10 to 14 days is recommended as a first-line treatment option, particularly in patients with any previous macrolide exposure or a penicillin allergy.

    As part of bismuth quadruple salvage therapy in adults.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 or 4 times daily in combination with bismuth subcitrate or subsalicylate, tetracycline, and a proton pump inhibitor for 14 days is recommended particularly in patients failing clarithromycin triple therapy. A subsequent repeat course of bismuth quadruple therapy may be considered after failed prior bismuth quadruple therapy.

    As part of levofloxacin-based salvage therapy in adults with a penicillin allergy who have failed initial bismuth quadruple therapy.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 or 4 times daily in combination with levofloxacin and a proton pump inhibitor for 14 days.

    As part of dual salvage therapy in adults with prior quinolone exposure and a penicillin allergy who have failed initial bismuth quadruple therapy.
    Oral dosage (immediate-release)
    Adults

    500 mg PO 3 or 4 times daily in combination with a high-dose proton pump inhibitor for 14 days.

    For the treatment of giardiasis†.
    Oral dosage (immediate-release)
    Adults

    250 mg PO every 8 hours for 5 to 7 days.

    Infants, Children, and Adolescents

    5 mg/kg/dose (Max: 250 mg/dose) PO every 8 hours for 5 to 7 days.

    For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, biliary tract infections (cholecystitis, cholangitis), complicated diverticulitis, neonatal necrotizing enterocolitis†, peritoneal dialysis-related peritonitis†, and peritoneal dialysis catheter-related infection†.
    For the treatment of unspecified intraabdominal infections.
    Oral dosage (immediate-release)
    Adults

    7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Intravenous dosage
    Adults

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    For the treatment of complicated community-acquired, healthcare-acquired, or hospital-acquired intraabdominal infections with adequate source control.
    Oral dosage
    Adults

    500 mg PO every 6 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis complicated by rupture, intraabdominal abscess, and complicated diverticulitis.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis complicated by rupture and intraabdominal abscess.

    Neonates older than 40 weeks postmenstrual age†

    10 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis. Although oral dosing is not specified in the guidelines for neonates, oral absorption of metronidazole is nearly complete, and the same dose that is given IV is given orally.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose PO every 8 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis. Although oral dosing is not specified in the guidelines for neonates, oral absorption of metronidazole is nearly complete, and the same dose that is given IV is given orally.

    Neonates 34 weeks postmenstrual age and younger†

    7.5 mg/kg/dose PO every 12 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis. Although oral dosing is not specified in the guidelines for neonates, oral absorption of metronidazole is nearly complete, and the same dose that is given IV is given orally.

    Intravenous dosage
    Adults

    500 mg IV every 6 to 12 hours or 1.5 g IV every 24 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis complicated by rupture and intraabdominal abscess.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided 8 hours as part of combination therapy for 3 to 7 days. Complicated infections include peritonitis complicated by rupture and intraabdominal abscess.

    Neonates older than 40 weeks postmenstrual age†

    7.5 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose IV every 8 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis.

    Neonates 34 weeks postmenstrual age and younger†

    7.5 mg/kg/dose IV every 12 hours as part of combination therapy for 7 to 10 days. Metronidazole is an option for necrotizing enterocolitis.

    For the treatment of uncomplicated intraabdominal infections.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 6 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Intravenous dosage
    Adults

    500 mg IV every 6 to 12 hours or 1.5 g IV once as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided 8 hours as part of combination therapy. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

    For the treatment of peritoneal dialysis-related peritonitis†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 hours for 21 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 14 to 21 days.

    For the treatment of peritoneal dialysis catheter-related infection†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 hours for at least 14 to 21 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for at least 14 to 28 days.

    For the treatment of acute appendicitis without perforation.
    Intravenous dosage
    Adults

    500 mg IV every 6 to 12 hours or 1.5 g IV once as part of combination therapy. Antibiotics should be discontinued within 24 hours.

    Children and Adolescents weighing 80 kg or more

    30 mg/kg/dose (Max: 1,500 mg/dose) IV once daily in combination with ceftriaxone. Antibiotics should be discontinued within 24 hours.

    Infants, Children, and Adolescents weighing less than 80 kg

    30 mg/kg/dose (Max: 1,000 mg/dose) IV once daily in combination with ceftriaxone. Antibiotics should be discontinued within 24 hours.

    For the treatment of appendicitis complicated by rupture.
    Intravenous dosage
    Adults

    500 mg IV every 6 to 12 hours or 1.5 g IV every 24 hours as part of combination therapy for 3 to 7 days.

    Children and Adolescents weighing 80 kg or more

    30 mg/kg/dose (Max: 1,500 mg/dose) IV once daily in combination with ceftriaxone for 3 to 7 days.

    Infants, Children, and Adolescents weighing less than 80 kg

    30 mg/kg/dose (Max: 1,000 mg/dose) IV once daily in combination with ceftriaxone for 3 to 7 days.

    For the treatment of tetanus†.
    Oral dosage (immediate-release)
    Adults

    500 mg PO every 6 hours for 7 to 10 days.

    Infants, Children, and Adolescents

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours for 7 to 10 days.

    Intravenous dosage
    Adults

    500 mg IV every 6 hours for 7 to 10 days.

    Infants, Children, and Adolescents

    22.5 to 40 mg/kg/day (Max: 2 g/day) IV divided every 6 to 8 hours for 7 to 10 days.

    Neonates older than 40 weeks postmenstrual age

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours for 7 to 10 days.

    Neonates 35 to 40 weeks postmenstrual age

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours for 7 to 10 days.

    Neonates 34 weeks postmenstrual age and younger

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours for 7 to 10 days.

    For the treatment of bacteremia and sepsis†.
    For the treatment of sepsis†.
    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours.   Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours. 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 deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

    Neonates older than 40 weeks postmenstrual age

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours. 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 deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.

    Neonates 35 to 40 weeks postmenstrual age

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours. 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 deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.

    Neonates 34 weeks postmenstrual age and younger

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.

    For the treatment of bacteremia.
    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours. The FDA-approved dosage is 15 mg/kg/dose IV once, then 7.5 mg/kg/dose (Max: 1 g/dose) IV every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 10 mg/kg/dose IV every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    15 mg/kg/dose IV once, then 7.5 mg/kg/dose IV every 12 hours.

    Oral dosage (immediate-release)
    Adults

    500 mg PO every 8 to 12 hours. The FDA-approved dosage is 7.5 mg/kg/dose (Max: 1 g/dose) PO every 6 hours for 7 to 10 days.

    Infants†, Children†, and Adolescents†

    10 mg/kg/dose (Max: 500 mg/dose) PO every 8 hours.

    Neonates older than 40 weeks postmenstrual age†

    10 mg/kg/dose PO every 8 hours.

    Neonates 35 to 40 weeks postmenstrual age†

    7.5 mg/kg/dose PO every 8 hours.

    Neonates 34 weeks postmenstrual age and younger†

    7.5 mg/kg/dose PO every 12 hours.

    For bacterial infection prophylaxis† after penetrating trauma.
    For bacterial infection prophylaxis after penetrating brain trauma with gross contamination or penetrating spinal cord trauma with abdominal cavity involvement†.
    Intravenous dosage
    Adults

    500 mg IV every 8 to 12 hours plus cefazolin for 5 days or until CSF leak is closed, whichever is longer.

    Infants, Children, and Adolescents

    22.5 to 40 mg/kg/day (Max: 1.5 g/day) IV divided every 8 hours plus cefazolin for 5 days or until CSF leak is closed, whichever is longer.

    For bacterial infection prophylaxis after penetrating chest trauma with esophageal disruption or penetrating abdominal trauma†.
    Intravenous dosage
    Adults

    500 mg IV every 6 to 8 hours plus cefazolin for 1 day after definitive washout.

    Infants, Children, and Adolescents

    22.5 to 40 mg/kg/day (Max: 2 g/day) IV divided every 6 to 8 hours plus cefazolin for 1 day after definitive washout.

    For the treatment of small intestinal bacterial overgrowth†.
    Oral dosage (immediate-release)
    Adults

    250 mg PO 3 times daily for 7 to 10 days.

    Children and Adolescents

    10 mg/kg/dose PO twice daily (Max: 750 mg/day) for 7 to 10 days.

    For the treatment of chorioamnionitis† or intraamniotic infection†.
    For the treatment of chorioamnionitis† or intraamniotic infection† after cesarean section as additive anaerobic coverage.
    Intravenous dosage
    Adults

    500 mg IV for at least 1 dose after umbilical cord clamping when ampicillin, cefazolin, or vancomycin is used in combination with gentamicin intrapartum.

    Adolescents

    500 mg IV for at least 1 dose after umbilical cord clamping when ampicillin, cefazolin, or vancomycin is used in combination with gentamicin intrapartum.

    For the treatment of chorioamnionitis† or intraamniotic infection† intrapartum as part of combination therapy.
    Intravenous dosage
    Adults

    500 mg IV every 8 hours during the intrapartum period as alternative combination therapy. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

    Adolescents

    500 mg IV every 8 hours during the intrapartum period as alternative combination therapy. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2,250 mg/day IV/PO is usual maximum; however, up to 4 g/day IV/PO in FDA-approved labeling.

    Geriatric

    2,250 mg/day IV/PO is usual maximum; however, up to 4 g/day IV/PO in FDA-approved labeling.

    Adolescents

    50 mg/kg/day (Max: 2,250 mg/day) PO; safety and efficacy of IV use have not been established; however, doses up to 40 mg/kg/day (Max: 2,250 mg/day) IV have been used off-label.

    Children

    50 mg/kg/day (Max: 2,250 mg/day) PO; safety and efficacy of IV use have not been established; however, doses up to 40 mg/kg/day (Max: 2,250 mg/day) IV have been used off-label.

    Infants

    50 mg/kg/day PO; safety and efficacy of IV have not been established; however, doses up to 40 mg/kg/day IV have been used off-label.

    Neonates

    Postmenstrual age (PMA) older than 40 weeks: Safety and efficacy have not been established; however, doses up to 30 mg/kg/day IV have been used off-label.
    PMA 35 to 40 weeks: Safety and efficacy have not been established; however, doses up to 22.5 mg/kg/day IV have been used off-label.
    PMA 34 weeks and younger: Safety and efficacy have not been established; however, doses up to 15 mg/kg/day IV have been used off-label.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Reduce the dose of systemic metronidazole by 50% in patients with severe hepatic impairment (Child-Pugh C). Single systemic doses may not need to be adjusted.

    Renal Impairment

    No dosage adjustment needed in adult patients. Metabolites will likely accumulate in patients with a CrCl less than 10 mL/minute. In pediatric patients with a CrCl less than 10 mL/minute/1.73 m2, a dose of 4 mg/kg/dose IV/PO every 6 hours is recommended (based on usual dose of 15 to 30 mg/kg/day divided every 6 to 8 hours).
     
    Intermittent hemodialysis
    No dosage adjustment is necessary in adult patients; however, administer systemic doses after hemodialysis. Systemically administered metronidazole is significantly removed (up to 65% of a dose) during a standard hemodialysis session. In pediatric patients, a dose of 4 mg/kg/dose IV/PO every 6 hours is recommended (based on usual dose of 15 to 30 mg/kg/day divided every 6 to 8 hours).
     
    Peritoneal dialysis
    No dosage adjustment is necessary in adult patients. The pharmacokinetic disposition of metronidazole is not significantly altered in patients undergoing CAPD. In pediatric patients, a dose of 4 mg/kg/dose IV/PO every 6 hours is recommended (based on usual dose of 15 to 30 mg/kg/day divided every 6 to 8 hours).
     
    Chronic renal replacement therapy (CRRT)
    No dosage adjustment is necessary.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Regular-release tablets or capsules: Administer without regard to meals.
    Extended-release tablets: Swallow whole; do not crush, break, or chew. Administer on an empty stomach, at least 1 hour before or 2 hours after meals.

    Oral Liquid Formulations

    Reconstitution for powder for oral suspension
    Available as a compounding kit containing 1 bottle of metronidazole powder and 1 bottle of grape-flavored diluent.
    Reconstitution produces a 50 mg/mL metronidazole oral suspension.
    Tap the bottom edges of the bottle containing the metronidazole powder on a hard surface to loosen the powder.
    Remove the cap from the bottle containing the metronidazole powder. Tap the top of the induction seal to loosen any powder which may have adhered to the seal. Slowly peel back the foil seal.
    Shake the diluent bottle for a few seconds prior to removing the cap.
    Open the diluent bottle and pour about half of the diluent into the metronidazole powder bottle.
    Replace the cap and shake the mixture bottle vigorously for approximately 60 seconds.
    Empty the remaining diluent into the metronidazole powder bottle. Allow remaining diluent to drain into the powder bottle for 10 seconds.
    Replace the cap and shake the mixture bottle vigorously for approximately 60 seconds.
    Wait at least 1 hour before administering the first dose.
    Storage: Store reconstituted solution at room temperature (15 to 30 degrees C; 59 to 86 degrees F); Do not freeze. Keep container tightly closed and protect from light. Discard any unused solution after 30 days.
     
    Administration for oral suspension
    Shake bottle vigorously prior to each administration.
    Measure dosage with calibrated spoon, cup, or oral syringe.

    Extemporaneous Compounding-Oral

    NOTE: Extemporaneously prepared suspensions are not FDA-approved.
     
    Extemporaneous preparation of 50 mg/mL metronidazole oral suspension:
    Using a mortar and pestle, grind 24 x 250 mg metronidazole tablets to a fine powder.
    To make the base solution: In a separate container, mix 1 of the following combinations: 1) 60 mL of Ora-Sweet with 60 mL of Ora-Plus; or 2) 60 mL of Ora-Sweet SF with 60 mL of Ora-Plus; or 3) 120 mL cherry syrup (cherry syrup concentrate diluted 1:4 with simple syrup).
    Add a small amount of the base solution to the fine powder and mix into a uniform paste. Add geometric amounts of the base solution and mix well after each addition.
    Transfer to a graduated cylinder and add additional base solution to make a total of 120 mL. Mix well.
    Place in amber plastic bottles. Shake well before each use.
    Storage: This oral suspension is stable for at least 60 days when stored at room temperature or refrigerated.
     
    Extemporaneous preparation of 10 mg/mL metronidazole oral suspension:
    Using a mortar and pestle, grind 5 x 250 mg metronidazole tablets to a fine powder.
    To make the base solution: In a separate container, mix 62.5 mL of Ora-Sweet with 62.5 mL of Ora-Plus and shake well.
    Add a small amount of the base solution to the fine powder and mix into a uniform paste. Add geometric amounts of the base solution and mix well after each addition.
    Transfer to a graduated cylinder and add additional base solution to make a total of 125 mL. Mix well.
    Place in amber plastic bottles. Shake well before each use.
    Storage: This oral suspension is stable for at least 90 days when stored at room temperature.

    Injectable Administration

    Administer by slow IV infusion only, either as a continuous or intermittent infusion.
    Do not admix with other drugs. If used with a primary intravenous fluid system, the primary solution should be discontinued during metronidazole infusion.
    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Preparation of Intravenous Infusion
    Supplied as 5 mg/mL ready to use single-use infusion bags. No dilution required prior to administration.
    Do not refrigerate.
     
    Intermittent Intravenous Infusion
    Remove from foil wrapping just prior to administration.
    Infuse by slow intermittent IV infusion over 30 to 60 minutes.
    Do not use in series connections; air embolism may occur.
    Do not use equipment containing aluminum (e.g., needles, cannulae) that would come in contact with the drug solution during administration as precipitates may form.

    Topical Administration

    Topical products differ in pH from vaginal products; therefore, topical cream, gel, and lotion are for topical application to the skin only. Do not use topical products orally or vaginally.
    Avoid contact with the eyes.
    Prior to administration, cleanse area with a mild, nonirritating cleanser.

    Cream/Ointment/Lotion Formulations

    Cream/Gel application: A thin layer should be rubbed into the affected areas. Cosmetics, sunscreens, and/or moisturizers may be used after applying cream, if needed.
    Lotion application: Apply a thin layer to entire affected areas. Cosmetics, sunscreens, and/or moisturizers may be applied after the lotion has dried and 5 minutes have passed.

    Intravaginal Administration

    Vaginal and topical products differ in pH, therefore, vaginal gel is for vaginal use only; do not use vaginal products orally or topically.
    Instruct patient on proper use.
    Use special applicator supplied by the manufacturer.

    STORAGE

    Flagyl:
    - Protect from light
    - Store at or below 77 degrees F
    Flagyl ER:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    - Store in a dry place
    Flagyl RTU:
    - Avoid excessive heat (above 104 degrees F)
    - Brief exposure up to 104 degrees F does not adversely affect product
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in original package until time of use
    MetroCream:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    MetroGel:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    MetroGel Vaginal:
    - Avoid extreme temperatures
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    MetroGel-Vaginal:
    - Avoid extreme temperatures
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    MetroLotion:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Noritate:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    NUVESSA:
    - Do not refrigerate
    - Protect from freezing
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Nydamax:
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Rosadan:
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Vandazole:
    - Avoid extreme temperatures
    - Protect from freezing
    - Store at room temperature (between 59 to 86 degrees F)
    Vitazol :
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Hematological disease

    Metronidazole is contraindicated in patients with a prior history of hypersensitivity to metronidazole or other nitroimidazole derivatives. Systemic metronidazole should be used with care in patients with evidence of or history of hematological disease; monitor complete blood count (CBC) in these patients. Agranulocytosis, leukopenia, and neutropenia have been associated with systemic metronidazole administration.

    Dialysis, renal failure, renal impairment

    Systemic metronidazole and its metabolites may accumulate significantly in patients with severe renal impairment or end stage renal disease (renal failure), including in patients receiving peritoneal dialysis, due to reduced urinary excretion. Monitor for metronidazole-associated adverse events.

    Apheresis, AV block, bradycardia, cardiomyopathy, celiac disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, pheochromocytoma, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    QT prolongation has been reported with metronidazole use, particularly when administered with other drugs with the potential to prolong the QT interval. Use metronidazole with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, persons 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    New primary malignancy

    Metronidazole, when given systemically, has been reported to be carcinogenic in mice and rats. Similar studies in the hamster gave negative results. Also, metronidazole has shown mutagenic activity in a number of in vitro assay systems, but studies in mammals (in vivo) failed to demonstrate a potential for genetic damage. Human data are not available to describe the risk of a new primary malignancy secondary to use. The boxed warning states that systemic metronidazole use should be reserved for conditions where the drug is clearly needed; avoid unnecessary use. Vaginal and topical forms of metronidazole do not carry the boxed warning regarding carcinogenicity.

    Alcoholism, ethanol ingestion, ethanol intoxication

    Oral, injectable, and intravaginal dosage forms of metronidazole should be used with caution in patients with alcoholism or ethanol intoxication. Metronidazole may interfere with the metabolism of ethanol, resulting in disulfiram-like effects. Patients should try to avoid ethanol ingestion to avoid the risk of undesirable side effects. It is recommended that alcoholic beverages or medicines not be used concurrently with metronidazole or for at least 3 days following the discontinuation of the drug. Psychotic reactions have been reported in alcoholic patients on metronidazole and disulfiram therapy.

    Fungal infection

    Metronidazole use may result in candidal overgrowth. Known or previously unrecognized candida fungal infection may present more prominent symptoms during therapy with metronidazole and requires treatment with an appropriate antifungal agent.

    Crohn's disease

    Crohn's disease patients are known to have an increased incidence of gastrointestinal and certain extraintestinal cancers. There have been some reports in the medical literature of breast and colon cancer in Crohn's disease patients who have been treated with metronidazole at high doses for extended periods of time. A cause and effect relationship has not been established.

    Ocular exposure

    Topical metronidazole gels or creams contain ingredients that may cause burning and irritation of the eye. In the event of accidental ocular exposure, rinse the eye with copious amounts of cool tap water.

    Hepatic disease, hepatic encephalopathy

    Reduce metronidazole dose in patients with severe hepatic disease or impairment (Child-Pugh C) or hepatic encephalopathy due to slowed metabolism and accumulation in plasma, which may cause exacerbations of CNS adverse events in patients with hepatic encephalopathy. Monitor patients with mild to moderate hepatic impairment for metronidazole-associated adverse effects.

    Cockayne syndrome

    Systemic metronidazole is contraindicated in patients with Cockayne syndrome. Cases of severe irreversible hepatotoxicity and acute hepatic failure, including fatal outcomes with very rapid onset after treatment initiation with systemic metronidazole, have been reported in these patients. The latency period from starting metronidazole to signs of liver failure was as short as 2 days.

    Corticosteroid therapy, edema, sodium restriction

    Use parenteral metronidazole with caution in patients requiring sodium restriction or corticosteroid therapy or in patients predisposed to edema. Certain formulations of parenteral metronidazole contain sodium.

    Laboratory test interference

    Systemic metronidazole therapy may cause laboratory test interference with certain laboratory measurements, such as AST, ALT, LDH, triglycerides, and hexokinase glucose; values of zero may be noted. All of the assays in which interference has been observed use enzymatic coupling of the assay to oxidation reduction of nicotinamide adenine dinucleotide. Interference is due to the similarity in the absorbance peaks of NADH (340 nm) and metronidazole (322 nm) at a pH of 7. Metronidazole causes an increase in ultraviolet absorbance at 340 nm resulting in falsely decreased values. Antimicrobials are also known to suppress H. pylori; thus, ingestion of these agents within 4 weeks of performing diagnostic tests for H. pylori may lead to false negative results. At a minimum, instruct the patient to avoid the use of metronidazole in the 4 weeks prior to the test.

    Geriatric

    Use metronidazole with caution in geriatric patients as they may also be at increased risk for QT prolongation. Additionally, geriatric patients may be likely to have hepatic impairment or renal impairment and the hepatic metabolism and/or renal clearance of metronidazole may be reduced. Therefore, monitoring of clinical response may be necessary to adjust the metronidazole dosage accordingly. No overall differences have been reported in safety and effectiveness between younger and older adult patients, but greater sensitivity of some older patients cannot be ruled out. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    Pregnancy

    Oral metronidazole is contraindicated during the first trimester of pregnancy in patients with trichomoniasis. However, guidelines suggest metronidazole use for trichomoniasis at any stage of pregnancy as studies have not demonstrated an association between metronidazole and teratogenic effects. For indications other than trichomoniasis, avoid metronidazole during pregnancy whenever possible, with use occurring only after careful assessment of the potential risk to benefit ratio. Available data on metronidazole use in pregnant women from published cohort studies, case-control studies, case series, meta-analyses, and case reports over several decades have not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproductive studies, no adverse developmental effects were demonstrated when oral metronidazole was administered at doses up to 6 times the recommended human dose. While not an animal teratogen, systemically absorbed metronidazole readily crosses the placenta and enters the fetal circulation. Reports in humans are conflicting, and the effects of metronidazole on human fetal organogenesis are not known. In a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, metronidazole use was not associated with an increased risk of major congenital malformations or organ specific major congenital malformations. However, in a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, metronidazole use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 1.7; 95% CI: 1.27 to 2.26; 53 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. There are no data regarding topical or vaginal metronidazole use during pregnancy; however, the mean Cmax and AUC after topical metronidazole 1 g daily for 7 days are less than 1% of those after a single 250 mg oral dose, and the mean Cmax and AUC after a single 5 g vaginal dose are approximately 2% and 4%, respectively, of those after a single 500 mg oral dose.

    Breast-feeding

    Metronidazole is excreted into breast milk. Breast-feeding is not recommended during treatment with systemic products. However, guidelines suggest that the usual metronidazole dose for the treatment of trichomoniasis during breast-feeding (500 mg PO twice daily for 7 days) is compatible with breast-feeding; however, consider deferring breast-feeding for 12 to 24 hours after maternal metronidazole use. Previous American Academy of Pediatrics (AAP) recommendations suggested breast-feeding may be resumed within 24 to 48 hours after the last dose of metronidazole treatment is completed. There are no data on the presence of metronidazole in human milk after intravaginal administration. Because of the possibility of some systemic absorption after intravaginal administration, interrupt breast-feeding for 48 hours after the last intravaginal dose and feed the infant with previously stored human breast milk or formula. The 0.75% vaginal gel achieves 2% of the mean maximum serum concentration of a 500 mg oral dose. Breast-feeding is not recommended during treatment with topical metronidazole. Metronidazole is a mutagen in vitro and has been shown to be carcinogenic in animal studies. In general, increased oral and rectal Candida colonization and loose stools have been reported in infants exposed to metronidazole via breast milk. In a study of 3 patients that received a single 2 g oral dose, peak milk concentrations ranged between 50 and 60 mcg/mL at 2 to 4 hours after the dose. If breast-feeding were to continue, the estimated infant exposure during the next 48 hours would be 25.3 mg; if breast-feeding was interrupted for 12 hours, the estimated 48-hour exposure would be 9.8 mg, and if breast-feeding was interrupted for 24 hours, the estimated 48 hour exposure would be 3.5 mg. In studies of women receiving 600 mg/day, metronidazole milk concentrations ranged from 1.1 to 15.2 mcg/mL and in patients receiving 1,200 mg/day concentrations ranged from 9.02 to 15.52 mcg/mL. The mean milk:plasma ratio in both groups was approximately 1, and the mean plasma concentrations in the exposed infants were approximately 20% of the maternal plasma concentration. Depending on the indication, oral vancomycin, amoxicillin; clavulanate, ampicillin; sulbactam, or clindamycin (systemic or intravaginal) may be potential alternatives to consider during breast-feeding. Assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Alternative antimicrobials that previous AAP recommendations considered as usually compatible with breast-feeding include clindamycin and penicillins.

    ADVERSE REACTIONS

    Severe

    aseptic meningitis / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    agranulocytosis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    angioedema / Rapid / Incidence not known
    Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    toxic epidermal necrolysis / Delayed / Incidence not known
    pancreatitis / Delayed / Incidence not known
    new primary malignancy / Delayed / Incidence not known
    serum sickness / Delayed / Incidence not known
    hepatic failure / Delayed / Incidence not known
    hepatotoxicity / Delayed / Incidence not known

    Moderate

    vaginitis / Delayed / 0-15.0
    candidiasis / Delayed / 0.2-12.0
    hypertension / Early / 1.1-1.1
    constipation / Delayed / 0-1.0
    depression / Delayed / 0-1.0
    dysuria / Early / 0-1.0
    ataxia / Delayed / Incidence not known
    neurotoxicity / Early / Incidence not known
    dysarthria / Delayed / Incidence not known
    peripheral neuropathy / Delayed / Incidence not known
    nystagmus / Delayed / Incidence not known
    encephalopathy / Delayed / Incidence not known
    confusion / Early / Incidence not known
    psychosis / Early / Incidence not known
    neutropenia / Delayed / Incidence not known
    eosinophilia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    erythema / Early / Incidence not known
    contact dermatitis / Delayed / Incidence not known
    phlebitis / Rapid / Incidence not known
    urinary incontinence / Early / Incidence not known
    cystitis / Delayed / Incidence not known
    stomatitis / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    glossitis / Early / Incidence not known
    proctitis / Delayed / Incidence not known
    dyspareunia / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    ST-T wave changes / Rapid / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    QT prolongation / Rapid / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    peripheral edema / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    headache / Early / 2.2-18.0
    vaginal discharge / Delayed / 12.0-12.0
    nausea / Early / 1.6-10.0
    metallic taste / Early / 2.0-9.0
    dysgeusia / Early / 2.0-9.0
    infection / Delayed / 0-7.0
    pruritus / Rapid / 1.6-6.0
    influenza / Delayed / 0-6.0
    abdominal pain / Early / 4.0-5.0
    pruritus ani / Early / 5.0-5.0
    diarrhea / Early / 1.0-4.0
    vomiting / Early / 0-4.0
    dizziness / Early / 0-4.0
    rhinitis / Early / 0-4.0
    pharyngitis / Delayed / 2.0-3.1
    dysmenorrhea / Delayed / 1.2-3.0
    sinusitis / Delayed / 1.4-3.0
    xerostomia / Early / 2.0-2.0
    nasal congestion / Early / 1.1-1.1
    flatulence / Early / 0-1.0
    anorexia / Delayed / 0-1.0
    dyspepsia / Early / 0-1.0
    gingivitis / Delayed / 0-1.0
    insomnia / Early / 0-1.0
    diaphoresis / Early / 0-1.0
    acne vulgaris / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    rash / Early / 1.0-1.0
    increased urinary frequency / Early / 0-1.0
    breast enlargement / Delayed / 0-1.0
    leukorrhea / Delayed / 0-1.0
    menorrhagia / Delayed / 0-1.0
    back pain / Delayed / 0-1.0
    vaginal irritation / Early / 9.0
    asthenia / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    drowsiness / Early / Incidence not known
    syncope / Early / Incidence not known
    weakness / Early / Incidence not known
    irritability / Delayed / Incidence not known
    paresthesias / Delayed / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    skin irritation / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    fever / Early / Incidence not known
    flushing / Rapid / Incidence not known
    ocular irritation / Rapid / Incidence not known
    xerosis / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    polyuria / Early / Incidence not known
    urine discoloration / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    myalgia / Early / Incidence not known
    arthralgia / Delayed / Incidence not known
    muscle cramps / Delayed / Incidence not known
    hiccups / Early / Incidence not known
    fatigue / Early / Incidence not known
    chills / Rapid / Incidence not known
    malaise / Early / Incidence not known

    DRUG INTERACTIONS

    Adagrasib: (Major) Concomitant use of adagrasib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Alfuzosin: (Moderate) Concomitant use of metronidazole and alfuzosin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Amiodarone: (Major) Concomitant use of metronidazole and amiodarone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Amisulpride: (Major) Concomitant use of metronidazole and amisulpride increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Amlodipine; Celecoxib: (Minor) Since celecoxib is metabolized by cytochrome P450 2C9, concurrent administration with metronidazole, which can inhibit this enzyme, may result in increased levels of celecoxib. The clinical significance of this interaction has not been established.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Concomitant use of metronidazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Anagrelide: (Major) Concomitant use of metronidazole and anagrelide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Apomorphine: (Moderate) Concomitant use of metronidazole and apomorphine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Aripiprazole: (Moderate) Concomitant use of metronidazole and aripiprazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Arsenic Trioxide: (Major) Concomitant use of metronidazole and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Artemether; Lumefantrine: (Major) Concomitant use of metronidazole and artemether increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Concomitant use of metronidazole and lumefantrine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Asenapine: (Major) Concomitant use of metronidazole and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Atomoxetine: (Moderate) Concomitant use of metronidazole and atomoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Azithromycin: (Major) Concomitant use of metronidazole and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Barbiturates: (Minor) Barbiturates may decrease the half-life and plasma concentrations of metronidazole. The clinical significance of this effect is uncertain.
    Bedaquiline: (Major) Concomitant use of metronidazole and bedaquiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Bortezomib: (Minor) Monitor patients for the development of peripheral neuropathy when receiving bortezomib in combination with other drugs that can cause peripheral neuropathy like metronidazole; the risk of peripheral neuropathy may be additive.
    Buprenorphine: (Major) Concomitant use of metronidazole and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Buprenorphine; Naloxone: (Major) Concomitant use of metronidazole and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Busulfan: (Major) Systemic metronidazole should not be administered with busulfan unless the benefit outweighs the risk. If no therapeutic alternatives to metronidazole exist, monitor busulfan concentrations and adjust the busulfan doses as necessary. Metronidazole may increase plasma concentrations of busulfan, which can result in an increased risk for serious busulfan toxicity such as sinusoidal obstruction syndrome, gastrointestinal mucositis, and hepatic veno-occlusive disease.
    Cabotegravir; Rilpivirine: (Moderate) Concomitant use of metronidazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Carbamazepine: (Minor) Monitor serum concentrations of carbamazepine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of carbamazepine; thereby, increasing the risk of side effects.
    Celecoxib: (Minor) Since celecoxib is metabolized by cytochrome P450 2C9, concurrent administration with metronidazole, which can inhibit this enzyme, may result in increased levels of celecoxib. The clinical significance of this interaction has not been established.
    Celecoxib; Tramadol: (Minor) Since celecoxib is metabolized by cytochrome P450 2C9, concurrent administration with metronidazole, which can inhibit this enzyme, may result in increased levels of celecoxib. The clinical significance of this interaction has not been established.
    Ceritinib: (Major) Concomitant use of metronidazole and ceritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Chloroquine: (Major) Concomitant use of metronidazole and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Chlorpromazine: (Major) Concomitant use of metronidazole and chlorpromazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Cholestyramine: (Moderate) Administer metronidazole at least 1 hour before or at least 4 to 6 hours after administration of cholestyramine. The oral bioavailability of metronidazole was reduced by 21% when given with cholestyramine.
    Cimetidine: (Moderate) Monitor for metronidazole-related adverse effects during concomitant cimetidine use. Cimetidine decreases hepatic microsomal liver enzyme activity and may prolong the half-life and decrease plasma clearance of metronidazole.
    Ciprofloxacin: (Moderate) Concomitant use of metronidazole and ciprofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Cisapride: (Contraindicated) Avoid concomitant use of metronidazole and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Citalopram: (Major) Concomitant use of metronidazole and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clarithromycin: (Major) Concomitant use of metronidazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Clofazimine: (Moderate) Concomitant use of clofazimine and metronidazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Clozapine: (Moderate) Concomitant use of metronidazole and clozapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Codeine; Promethazine: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Crizotinib: (Major) Concomitant use of metronidazole and crizotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Cyclophosphamide: (Moderate) Monitor for an increase in cyclophosphamide-related adverse reactions if coadministration with metronidazole is necessary. Acute encephalopathy has been reported in one patient receiving cyclophosphamide and metronidazole, although causal association is unclear. In an animal study, the combination of cyclophosphamide with metronidazole was associated with an increase in cyclophosphamide toxicity.
    Cyclosporine: (Major) Monitor serum concentrations of cyclosporine when coadministered with systemic metronidazole. Concomitant use with metronidazole may increase the serum concentrations of cyclosporine; thereby, increasing the risk of side effects. Also, medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after metronidazole is discontinued. Cyclosporine parenteral and oral solutions contain ethanol; liquid-filled capsules contain ethanol in lower percentages. Administration of ethanol-containing formulations of cyclosporine to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Ritonavir oral solution and capsules contain ethanol. Administration of ritonavir oral solution or capsules to patients receiving or who have recently received disulfiram or metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets, oral powder).
    Dasatinib: (Moderate) Concomitant use of metronidazole and dasatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Degarelix: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., degarelix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Desflurane: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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.
    Deutetrabenazine: (Moderate) Concomitant use of metronidazole and deutetrabenazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with deutetrabenazine is not clinically significant when administered within the recommended dosage range.
    Dextromethorphan; Quinidine: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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.
    Disopyramide: (Major) Concomitant use of metronidazole and disopyramide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Disulfiram: (Contraindicated) The combination of systemic metronidazole and disulfiram is contraindicated. Do not administer systemic metronidazole concomitantly or within 2 weeks after the administration of disulfiram because additive CNS toxic effects can occur. Case reports have described the development of CNS toxicity after metronidazole was coadministered with disulfiram, resulting in psychosis and confusion. This toxicity is believed to occur because of combined inhibition of aldehyde dehydrogenase. When metronidazole and disulfiram are combined, symptoms may become evident within 10 to 14 days, and symptoms may remain for 2 to 3 days after the drugs are discontinued.
    Dofetilide: (Major) Concomitant use of metronidazole and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Dolasetron: (Moderate) Concomitant use of metronidazole and dolasetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Dolutegravir; Rilpivirine: (Moderate) Concomitant use of metronidazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Donepezil: (Moderate) Concomitant use of metronidazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Donepezil; Memantine: (Moderate) Concomitant use of metronidazole and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as metronidazole, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
    Dronabinol: (Major) The use of metronidazole within 14 days of beginning therapy with dronabinol oral solution is contraindicated, due to the risk of a disulfiram-like reaction. Do not administer metronidazole within 7 days of completing therapy with the oral solution. Dronabinol oral solution contains 50% (w/w) dehydrated alcohol and 5% (w/w) propylene glycol, which can produce disulfiram-like reactions (e.g., abdominal cramps, nausea/vomiting, headaches, and flushing) with drugs such as metronidazole. Ethanol competitively inhibits the metabolism of propylene glycol; however, the contribution of propylene glycol to these reactions is unknown. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations (e.g., dronabinol oral capsules).
    Dronedarone: (Contraindicated) Avoid concomitant use of metronidazole and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Droperidol: (Major) Concomitant use of metronidazole and droperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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: (Moderate) Concomitant use of metronidazole and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of metronidazole and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of metronidazole and efavirenz may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    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.
    Eliglustat: (Moderate) Concomitant use of metronidazole and eliglustat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Concomitant use of metronidazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Concomitant use of metronidazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Encorafenib: (Major) Concomitant use of metronidazole and encorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Entrectinib: (Major) Concomitant use of metronidazole and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Eribulin: (Major) Concomitant use of metronidazole and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Erythromycin: (Major) Concomitant use of metronidazole and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Escitalopram: (Moderate) Concomitant use of metronidazole and escitalopram may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Estradiol; Levonorgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norethindrone: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Estradiol; Norgestimate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethanol: (Major) Advise patients to discontinue alcohol-containing beverages and other forms of alcohol (including medicines with significant alcohol content and any products containing propylene glycol) before, during, and up to 3 days after therapy with systemic metronidazole. Disulfiram-like side effects including nausea, vomiting, tachycardia, headache, flushing, and abdominal cramps may occur if used together. (Moderate) Although the injection of alcohol used for therapeutic procedures is not expected to produce significant systemic effects of ethanol, use caution with concomitant use of metronidazole. Disulfiram-like side effects, including nausea, vomiting, tachycardia, headache, flushing, and abdominal cramps, may occur.
    Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norelgestromin: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norethindrone Acetate: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethinyl Estradiol; Norgestrel: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Etonogestrel; Ethinyl Estradiol: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Fingolimod: (Moderate) Concomitant use of metronidazole and fingolimod may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Flecainide: (Major) Concomitant use of metronidazole and flecainide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Floxuridine: (Minor) Enhancement of toxicity of fluorouracil, 5-FU, has been reported in a limited number of patients during concurrent treatment with metronidazole. This toxicity occurred without an increase in efficacy of fluorouracil. Toxicity may manifest as granulocytopenia, oral ulceration, anemia, and nausea and vomiting. This interaction is believed to occur through reduced clearance of fluorouracil. Floxuridine is a deoxyribonucleoside derivative of fluorouracil and may interact with metronidazole in a similar manner.
    Fluconazole: (Moderate) Concomitant use of metronidazole and fluconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Fluorouracil, 5-FU: (Minor) Caution is warranted with the coadministration of systemic metronidazole and systemic fluorouracil, 5-FU. Concomitant use with metronidazole may increase the serum concentrations of fluorouracil; thereby, increasing the risk of side effects. Toxicity may manifest as granulocytopenia, oral ulceration, anemia, and nausea and vomiting.
    Fluoxetine: (Moderate) Concomitant use of metronidazole and fluoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Fluphenazine: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and fluphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
    Fluvoxamine: (Moderate) Concomitant use of metronidazole and fluvoxamine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Foscarnet: (Major) Concomitant use of metronidazole and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Fosphenytoin: (Moderate) Monitor phenytoin concentrations and for loss of metronidazole efficacy during concomitant therapy with fosphenytoin. Fosphenytoin may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations; impaired clearance of phenytoin has also been reported.
    Fostemsavir: (Moderate) Concomitant use of metronidazole and fostemsavir may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 4 times the recommended daily dose.
    Gemifloxacin: (Moderate) Concomitant use of metronidazole and gemifloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Gemtuzumab Ozogamicin: (Moderate) Concomitant use of metronidazole and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Gilteritinib: (Moderate) Concomitant use of metronidazole and gilteritinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Glasdegib: (Major) Concomitant use of metronidazole and glasdegib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Goserelin: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., goserelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Granisetron: (Moderate) Concomitant use of metronidazole and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Halogenated Anesthetics: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Haloperidol: (Moderate) Concomitant use of metronidazole and haloperidol may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The intravenous route may carry a higher risk for haloperidol-induced QT/QTc prolongation than other routes of administration.
    Histrelin: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Hydroxychloroquine: (Major) Concomitant use of metronidazole and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Hydroxyzine: (Moderate) Concomitant use of metronidazole and hydroxyzine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Ibutilide: (Major) Concomitant use of metronidazole and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Iloperidone: (Major) Concomitant use of metronidazole and iloperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Inotuzumab Ozogamicin: (Major) Concomitant use of metronidazole and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Isoflurane: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Itraconazole: (Moderate) Concomitant use of metronidazole and itraconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Ivosidenib: (Major) Concomitant use of metronidazole and ivosidenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ixabepilone: (Contraindicated) Medications with significant alcohol content should not be administered during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. The supplied diluent that must be used for reconstitution of ixabepilone has a high concentration of dehydrated alcohol (39.8% w/v). Administration of ixabepilone to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions.
    Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and metronidazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval, like ketoconazole.
    Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concomitant use of metronidazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lapatinib: (Moderate) Concomitant use of metronidazole and lapatinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Lefamulin: (Major) Concomitant use of metronidazole and lefamulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Lenvatinib: (Major) Concomitant use of metronidazole and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Leuprolide: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Leuprolide; Norethindrone: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (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.
    Levofloxacin: (Moderate) Concomitant use of metronidazole and levofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and metronidazole due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. QT prolongation has been reported, particularly when metronidazole was administered with drugs with the potential for prolonging the QT interval, like ketoconazole.
    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) Concomitant use of lithium and metronidazole may increase serum lithium concentrations and increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Monitor serum lithium concentrations; reduce the lithium dose based on lithium serum concentrations and clinical response. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Lofexidine: (Major) Concomitant use of metronidazole and lofexidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Loperamide: (Moderate) Concomitant use of metronidazole and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Loperamide; Simethicone: (Moderate) Concomitant use of metronidazole and loperamide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Lopinavir; Ritonavir: (Major) Concomitant use of metronidazole and lopinavir; ritonavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Ritonavir oral solution and capsules contain ethanol. Administration of ritonavir oral solution or capsules to patients receiving or who have recently received disulfiram or metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets, oral powder).
    Macimorelin: (Major) Concomitant use of metronidazole and macimorelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Maprotiline: (Moderate) Concomitant use of metronidazole and maprotiline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Mebendazole: (Major) Avoid the concomitant use of mebendazole and metronidazole. Serious skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with coadministration.
    Mefloquine: (Moderate) Concomitant use of metronidazole and mefloquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Meperidine; Promethazine: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    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.
    Methadone: (Major) Concomitant use of metronidazole and methadone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Midostaurin: (Major) Concomitant use of metronidazole and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mifepristone: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mirtazapine: (Moderate) Concomitant use of metronidazole and mirtazapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Mobocertinib: (Major) Concomitant use of mobocertinib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Moxifloxacin: (Major) Concomitant use of metronidazole and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Mycophenolate: (Moderate) Coadministration of mycophenolate mofetil, norfloxacin, and metronidazole is not recommended. Administration of all 3 drugs significantly reduced the systemic exposure of mycophenolic acid. Specifically, as compared with the value obtained with mycophenolate mofetil monotherapy, the mean mycophenolic acid AUC (0 to 48 h) was decreased by 33% when 1 gram of mycophenolate mofetil was administered to healthy patients who had received 4 days of both norfloxacin and metronidazole. The mycophenolic acid systemic exposure was slightly reduced when mycophenolate mofetil was coadministered with either norfloxacin or metronidazole. The mean (+/-SD) mycophenolic acid AUC (0 to 48 h) was 56.2 (+/-24) mcgh/ml after mycophenolate mofetil monotherapy, 48.3 (+/-24) mcgh/ml after coadministration with norfloxacin, and 42.7 (+/-23) mcgh/ml after coadministration with metronidazole. Addtionally, potential QT prolongation has been reported in limited case reports with metronidazole; therefore, it should be used cautiously when adminstered with norfloxacin, which has a possible risk for QT prolongation and TdP.
    Nanoparticle Albumin-Bound Sirolimus: (Moderate) Although an interaction between metronidazole and sirolimus has not been studied, metronidazole has been reported to interact with tacrolimus. Specifically, a renal transplant patient reportedly had an increase in tacrolimus and cyclosporine serum concentrations when metronidazole was added to the drug regimen. A similar interaction may potentially occur with sirolimus.
    Nilotinib: (Major) Concomitant use of metronidazole and nilotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Nirmatrelvir; Ritonavir: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Ritonavir oral solution and capsules contain ethanol. Administration of ritonavir oral solution or capsules to patients receiving or who have recently received disulfiram or metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets, oral powder).
    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.
    Ofloxacin: (Moderate) Concomitant use of metronidazole and ofloxacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Olanzapine: (Moderate) Concomitant use of metronidazole and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Olanzapine; Fluoxetine: (Moderate) Concomitant use of metronidazole and fluoxetine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Concomitant use of metronidazole and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Olanzapine; Samidorphan: (Moderate) Concomitant use of metronidazole and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Ritonavir oral solution and capsules contain ethanol. Administration of ritonavir oral solution or capsules to patients receiving or who have recently received disulfiram or metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets, oral powder).
    Ondansetron: (Major) Concomitant use of metronidazole and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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.
    Osilodrostat: (Moderate) Concomitant use of metronidazole and osilodrostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Osimertinib: (Major) Concomitant use of metronidazole and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Oxaliplatin: (Major) Concomitant use of metronidazole and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ozanimod: (Major) Concomitant use of metronidazole and ozanimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ozanimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
    Paclitaxel: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Some formulations of paclitaxel contain a high level of ethanol. Administration to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
    Pacritinib: (Major) Concomitant use of pacritinib and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Paliperidone: (Major) Concomitant use of metronidazole and paliperidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Panobinostat: (Major) Concomitant use of metronidazole and panobinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pasireotide: (Moderate) Concomitant use of metronidazole and pasireotide may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Pazopanib: (Major) Concomitant use of metronidazole and pazopanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pentamidine: (Major) Concomitant use of pentamidine and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Perphenazine: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and perphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
    Perphenazine; Amitriptyline: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and perphenazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
    Phenytoin: (Moderate) Monitor phenytoin concentrations and for loss of metronidazole efficacy during concomitant therapy. Phenytoin may accelerate the elimination of metronidazole, resulting in reduced plasma concentrations; impaired clearance of phenytoin has also been reported.
    Pimavanserin: (Major) Concomitant use of metronidazole and pimavanserin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Pimozide: (Contraindicated) Avoid concomitant use of metronidazole and pimozide due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Pitolisant: (Major) Concomitant use of metronidazole and pitolisant increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ponesimod: (Major) Concomitant use of metronidazole and ponesimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Ponesimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
    Posaconazole: (Moderate) Concomitant use of metronidazole and posaconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Primaquine: (Moderate) Concomitant use of metronidazole and primaquine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Procainamide: (Major) Concomitant use of metronidazole and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Prochlorperazine: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and prochlorperazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
    Promethazine: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Promethazine; Dextromethorphan: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Promethazine; Phenylephrine: (Moderate) Concomitant use of metronidazole and promethazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Propafenone: (Major) Concomitant use of metronidazole and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quetiapine: (Major) Concomitant use of metronidazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quinidine: (Major) Concomitant use of metronidazole and quinidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Quinine: (Major) Concomitant use of metronidazole and quinine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ramelteon: (Moderate) Coadministration of ramelteon with inhibitors of CYP2C9, such as metronidazole, may lead to increases in the serum concentrations of ramelteon.
    Ranolazine: (Moderate) Concomitant use of metronidazole and ranolazine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Relugolix: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., relugolix) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (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.
    Ribociclib: (Major) Concomitant use of metronidazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Ribociclib; Letrozole: (Major) Concomitant use of metronidazole and ribociclib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Rilpivirine: (Moderate) Concomitant use of metronidazole and rilpivirine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Risperidone: (Moderate) Concomitant use of metronidazole and risperidone may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Ritonavir: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. Ritonavir oral solution and capsules contain ethanol. Administration of ritonavir oral solution or capsules to patients receiving or who have recently received disulfiram or metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations of ritonavir (e.g., tablets, oral powder).
    Romidepsin: (Moderate) Concomitant use of metronidazole and romidepsin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Saquinavir: (Major) Concomitant use of metronidazole and saquinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    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.
    Selpercatinib: (Major) Concomitant use of metronidazole and selpercatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sertraline: (Moderate) Concomitant use of metronidazole and sertraline may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Sevoflurane: (Major) Concomitant use of metronidazole and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Siponimod: (Major) Concomitant use of metronidazole and siponimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sirolimus: (Moderate) Although an interaction between metronidazole and sirolimus has not been studied, metronidazole has been reported to interact with tacrolimus. Specifically, a renal transplant patient reportedly had an increase in tacrolimus and cyclosporine serum concentrations when metronidazole was added to the drug regimen. A similar interaction may potentially occur with sirolimus.
    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.
    Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and metronidazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Solifenacin: (Moderate) Concomitant use of metronidazole and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Sorafenib: (Major) Concomitant use of metronidazole and sorafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sotalol: (Major) Concomitant use of metronidazole and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Sunitinib: (Moderate) Concomitant use of metronidazole and sunitinib may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Tacrolimus: (Moderate) Concomitant use of metronidazole and tacrolimus may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Tamoxifen: (Moderate) Concomitant use of metronidazole and tamoxifen may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Telavancin: (Moderate) Concomitant use of metronidazole and telavancin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Tetrabenazine: (Major) Concomitant use of tetrabenazine and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Thalidomide: (Moderate) Thalidomide and other agents that cause peripheral neuropathy such as metronidazole should be used cautiously due to the potential for additive effects.
    Thioridazine: (Contraindicated) Avoid concomitant use of metronidazole and thioridazine due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
    Tipranavir: (Major) Medications with significant alcohol content should not be ingested during therapy with metronidazole and should be avoided for 3 days after therapy is discontinued. The Aptivus brand of tipranavir capsules contain alcohol. Administration of Aptivus capsules to patients receiving or who have recently received metronidazole may result in disulfiram-like reactions. A disulfiram reaction would not be expected to occur with non-ethanol containing formulations.
    Tolterodine: (Moderate) Concomitant use of metronidazole and tolterodine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The risk for tolterodine-associated QT/QTc prolongation may be increased in poor CYP2D6 metabolizers.
    Toremifene: (Major) Concomitant use of toremifene and metronidazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Trazodone: (Major) Concomitant use of metronidazole and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Triclabendazole: (Moderate) Concomitant use of triclabendazole and metronidazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Trifluoperazine: (Minor) QT/QTc prolongation can occur with concomitant use of metronidazole and trifluoperazine although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP.
    Triptorelin: (Moderate) Concomitant use of metronidazole and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Vandetanib: (Major) Concomitant use of metronidazole and vandetanib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Vardenafil: (Moderate) Concomitant use of metronidazole and vardenafil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Vecuronium: (Minor) Caution is warranted with the coadministration of systemic metronidazole and vecuronium. Metronidazole may potentiate the effects of vecuronium.
    Vemurafenib: (Major) Concomitant use of metronidazole and vemurafenib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Venlafaxine: (Moderate) Concomitant use of metronidazole and venlafaxine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Voclosporin: (Moderate) Concomitant use of metronidazole and voclosporin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at three times the maximum recommended dose.
    Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concomitant use of metronidazole and clarithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
    Voriconazole: (Moderate) Concomitant use of metronidazole and voriconazole may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Vorinostat: (Moderate) Concomitant use of metronidazole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
    Warfarin: (Moderate) Monitor prothrombin time and INR and watch for signs of bleeding with concomitant use of systemic metronidazole and warfarin. Warfarin dose adjustments may be necessary. Metronidazole can potentiate the anticoagulant effect of warfarin, resulting in prolongation of prothrombin time and increased risk of bleeding.
    Ziprasidone: (Major) Concomitant use of metronidazole and ziprasidone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.

    PREGNANCY AND LACTATION

    Pregnancy

    Oral metronidazole is contraindicated during the first trimester of pregnancy in patients with trichomoniasis. However, guidelines suggest metronidazole use for trichomoniasis at any stage of pregnancy as studies have not demonstrated an association between metronidazole and teratogenic effects. For indications other than trichomoniasis, avoid metronidazole during pregnancy whenever possible, with use occurring only after careful assessment of the potential risk to benefit ratio. Available data on metronidazole use in pregnant women from published cohort studies, case-control studies, case series, meta-analyses, and case reports over several decades have not established a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproductive studies, no adverse developmental effects were demonstrated when oral metronidazole was administered at doses up to 6 times the recommended human dose. While not an animal teratogen, systemically absorbed metronidazole readily crosses the placenta and enters the fetal circulation. Reports in humans are conflicting, and the effects of metronidazole on human fetal organogenesis are not known. In a large population-based cohort study (n = 139,938 live births) assessing antibiotic exposure during the first trimester of pregnancy (n = 15,469 exposures) and the risk of major birth defects, metronidazole use was not associated with an increased risk of major congenital malformations or organ specific major congenital malformations. However, in a nested, case-control study (n = 87,020 controls; 8,702 cases) within the Quebec Pregnancy Cohort, metronidazole use during early pregnancy was associated with an increased risk of spontaneous abortion (adjusted odds ratio (aOR) 1.7; 95% CI: 1.27 to 2.26; 53 exposed cases); residual confounding by severity of infection may be a potential limitation of this study. There are no data regarding topical or vaginal metronidazole use during pregnancy; however, the mean Cmax and AUC after topical metronidazole 1 g daily for 7 days are less than 1% of those after a single 250 mg oral dose, and the mean Cmax and AUC after a single 5 g vaginal dose are approximately 2% and 4%, respectively, of those after a single 500 mg oral dose.

    Metronidazole is excreted into breast milk. Breast-feeding is not recommended during treatment with systemic products. However, guidelines suggest that the usual metronidazole dose for the treatment of trichomoniasis during breast-feeding (500 mg PO twice daily for 7 days) is compatible with breast-feeding; however, consider deferring breast-feeding for 12 to 24 hours after maternal metronidazole use. Previous American Academy of Pediatrics (AAP) recommendations suggested breast-feeding may be resumed within 24 to 48 hours after the last dose of metronidazole treatment is completed. There are no data on the presence of metronidazole in human milk after intravaginal administration. Because of the possibility of some systemic absorption after intravaginal administration, interrupt breast-feeding for 48 hours after the last intravaginal dose and feed the infant with previously stored human breast milk or formula. The 0.75% vaginal gel achieves 2% of the mean maximum serum concentration of a 500 mg oral dose. Breast-feeding is not recommended during treatment with topical metronidazole. Metronidazole is a mutagen in vitro and has been shown to be carcinogenic in animal studies. In general, increased oral and rectal Candida colonization and loose stools have been reported in infants exposed to metronidazole via breast milk. In a study of 3 patients that received a single 2 g oral dose, peak milk concentrations ranged between 50 and 60 mcg/mL at 2 to 4 hours after the dose. If breast-feeding were to continue, the estimated infant exposure during the next 48 hours would be 25.3 mg; if breast-feeding was interrupted for 12 hours, the estimated 48-hour exposure would be 9.8 mg, and if breast-feeding was interrupted for 24 hours, the estimated 48 hour exposure would be 3.5 mg. In studies of women receiving 600 mg/day, metronidazole milk concentrations ranged from 1.1 to 15.2 mcg/mL and in patients receiving 1,200 mg/day concentrations ranged from 9.02 to 15.52 mcg/mL. The mean milk:plasma ratio in both groups was approximately 1, and the mean plasma concentrations in the exposed infants were approximately 20% of the maternal plasma concentration. Depending on the indication, oral vancomycin, amoxicillin; clavulanate, ampicillin; sulbactam, or clindamycin (systemic or intravaginal) may be potential alternatives to consider during breast-feeding. Assess site of infection, patient factors, local susceptibility patterns, and specific microbial susceptibility before choosing an alternative agent. Vancomycin is excreted in breast milk; however, absorption from the GI tract of any ingested vancomycin would be minimal. Alternative antimicrobials that previous AAP recommendations considered as usually compatible with breast-feeding include clindamycin and penicillins.

    MECHANISM OF ACTION

    Metronidazole is amebicidal, bactericidal, and trichomonicidal. Unionized metronidazole is readily taken up by passive diffusion and activated in the cytoplasm of susceptible anaerobic organisms and cells. Its selectivity for anaerobic bacteria is a result of the ability of these organisms to reduce metronidazole to its active form intracellularly. This process includes intracellular electron transport proteins such as ferredoxin, transfer of an electron to the nitro group of the metronidazole, and formation of a short-lived nitroso free radical. The electron transport proteins necessary for this reaction are found only in anaerobic bacteria. Due to the alteration of the metronidazole molecule, a concentration gradient is created and maintained which promotes the drug's intracellular transport. Reduced metronidazole and free radicals can interact with DNA leading to inhibition of DNA synthesis and DNA degradation. This eventually results in bacterial cell death. Metronidazole is equally effective against dividing and nondividing cells. The precise mechanism of action is unclear.[28581] [52483]
     
    Metronidazole also has immunosuppressive and anti-inflammatory actions, and it has been used in patients with rosacea. The antimicrobial actions of metronidazole alter the bacterial metabolism of bile acids in the GI tract, decreasing pruritus in patients with cholestasis secondary to primary biliary cirrhosis.[24103]
     
    The susceptibility interpretive criteria for metronidazole are delineated by pathogen. The MICs are defined for anaerobes as susceptible at 8 mcg/mL or less, intermediate at 16 mcg/mL, and resistant at 32 mcg/mL or more.[63320] [63321]
     
    The mechanism of resistance for metronidazole appears to be multifactorial and includes decreased drug uptake, higher efflux activity, and/or altered nitroreductase activity.

    PHARMACOKINETICS

    Metronidazole is administered orally, intravenously, intravaginally, and topically. Protein binding is less than 20%. Metronidazole is widely distributed into various body tissues and fluids including cerebrospinal fluid (CSF), pelvic tissue and peritoneal fluid, pancreas, colorectal tissue, bone, saliva, and gingival fluid. CSF concentrations of metronidazole are similar to plasma concentrations. Bactericidal concentrations of metronidazole have also been detected in pus from hepatic abscesses.
     
    Metronidazole is extensively metabolized in the liver by hydroxylation, oxidation, and glucuronide conjugation. The major metabolite is 2-hydroxymethyl metronidazole, which has some antibacterial and antiprotozoal activity (30% to 65% of metronidazole). The major route of elimination of metronidazole and its metabolites is via the urine (60% to 80% of the dose), with approximately 20% appearing as unchanged metronidazole. Fecal excretion accounts for 6% to 15% of the dose. Metronidazole is cleared by the kidneys at a rate of 10 mL/minute/1.73 m2. The mean elimination half-life is approximately 8 hours.
     
    Affected cytochrome P450 isoenzymes and drug transporters: none
    Although previously reported as an inhibitor of CYP3A4 based on assumptions inferred from isolated case reports, controlled in vitro and in vivo studies show that metronidazole does not significantly inhibit CYP3A4/5 activity. Additionally, a study in humans examined S-warfarin and tolbutamide as probes for the CYP2C9 isoenzyme. Metronidazole interacted with S-warfarin, but not tolbutamide. This lessens the likelihood of a potential CYP2C9 interaction, which was originally postulated. It is unknown whether metronidazole alters transport proteins.

    Oral Route

    Immediate-release formulations
    Metronidazole is well absorbed after oral administration (bioavailability more than 90%). Peak concentrations (Cmax) occur 1 to 2 hours after administration.
     
    Extended-release tablets
    Food increases the rate of absorption. The Cmax occurs approximately 4.6 and 6.8 hours after administration under fed and fasted conditions, respectively.

    Intravenous Route

    After IV administration, the plasma concentrations are proportional to the administered dose. An 8-hour IV infusion of 100 to 4,000 mg of metronidazole showed a linear relationship between dose and peak plasma concentration.

    Topical Route

    Topically applied metronidazole products are only minimally absorbed. Peak concentrations of the lotion are approximately 80 times lower than the peak concentrations of a single 250 mg oral dose. The mean Cmax and AUC are less than 1% of the value reported for a single 250 mg oral dose.

    Other Route(s)

    Intravaginal Route
    Intravaginally administered metronidazole is absorbed systemically; but peak serum concentrations (Cmax) and exposure (AUC) are 2% and 4%, respectively, of the concentrations achieved with 500 mg oral doses. The Cmax is achieved approximately 9.5 hours (range, 4 to 17 hours) after administration.