Version July 2025
The FDA has requested that Azurity Pharmaceuticals stop distributing unapproved drugs marketed as "Unit-of-Use Prescription Compounding Kits," including FIRST Lansoprazole, FIRST Pantoprazole, and FIRST Metronidazole. These kits have not been proven safe and effective and do not qualify for exemptions under the compounding provisions in sections 503A and 503B of the Federal Food, Drug and Cosmetic Act.
Further information may be found at https://www.fda.gov/drugs/enforcement-activities-fda/fda-notification-regarding-unapproved-drugs-included-kits.
Metronidazole has been shown to be carcinogenic in mice and rats. Avoid unnecessary use of metronidazole. Reserve metronidazole for use in the following indications: trichomoniasis, amebiasis, and anaerobic bacterial infections.
Amebiasis, intestinal (acute dysentery) or extraintestinal (liver abscess): Oral: 500 to 750 mg every 8 hours for 7 to 10 days followed by an intraluminal agent (eg, paromomycin) (Ref).
Bacterial vaginosis:
Note: Treatment is generally not warranted for patients who are asymptomatic (Ref).
Oral: 500 mg twice daily for 7 days (Ref). For multiple disease recurrences, 500 mg twice daily for 7 days in combination with or prior to a multiweek course of boric acid, followed by suppressive topical therapy (Ref).
Balantidiasis (alternative agent) (off-label use): Oral: 500 to 750 mg 3 times daily for 5 days (Ref).
Bite wound infection, prophylaxis or treatment (animal or human bite) (alternative agent) (off-label use): Oral, IV: 500 mg every 8 hours as part of an appropriate combination regimen (Ref). Duration is 3 to 5 days for prophylaxis; for established infection, continue for 1 to 2 days after resolution, typically 5 to 14 days total, although deep or complicated infection may require a longer duration (Ref).
Clostridioides difficile infection, treatment (off-label use):
Note: Criteria for disease severity is based on expert opinion and should not replace clinical judgment (Ref).
Nonsevere (ie, WBC ≤15,000 cells/mm3 and serum creatinine <1.5 mg/dL), initial episode (alternative agent if oral vancomycin or fidaxomicin unavailable or contraindicated): Oral: 500 mg 3 times daily for 10 to 14 days (Ref).
Fulminant infection (ie, ileus, megacolon, and/or hypotension/shock): IV: 500 mg every 8 hours in combination with oral and/or rectal vancomycin for 10 days; may be extended up to 14 days if patient has improved but has not had symptom resolution (Ref).
Crohn disease (off-label use):
Management after surgical resection:
Monotherapy: Oral: 20 mg/kg/day (in 3 divided doses) or 1 to 2 g/day in divided doses for 3 months (Ref); begin as soon as oral intake is resumed after surgery (Ref).
Combination therapy: Oral: 250 mg 3 times daily (Ref) or 1 to 2 g/day in divided doses for 3 months (Ref); begin as soon as oral intake is resumed after surgery and administer in combination with a thiopurine (azathioprine or mercaptopurine) or a TNF-alpha inhibitor (eg, adalimumab) (Ref).
Treatment of simple perianal fistulas (adjunctive agent): Oral: 500 mg twice daily for 4 weeks initially; if clinical response (ie, cessation of drainage and closure of fistula), continue at 250 mg 3 times daily for an additional 4 weeks (Ref) or 10 to 20 mg/kg/day in divided doses for 4 to 8 weeks with or without ciprofloxacin (Ref).
Giardiasis (alternative agent) (off-label use): Oral: 250 mg 3 times daily or 500 mg 2 times daily for 5 to 7 days (Ref).
Helicobacter pylori eradication (off-label use):
Bismuth quadruple regimen: Oral: Metronidazole 500 mg 3 or 4 times daily in combination with either bismuth subsalicylate or bismuth subcitrate, tetracycline, and a proton pump inhibitor (PPI); continue regimen for 14 days (Ref).
Levofloxacin triple regimen (in patients with penicillin allergy): Oral: Metronidazole 500 mg twice daily, in combination with levofloxacin plus a PPI; continue regimen for 14 days (Ref). Note: Levofloxacin sensitivity testing should be performed prior to using this regimen (Ref).
Intra-abdominal infection:
Note: Empiric oral regimens may be appropriate for patients with mild to moderate infection. Other patients may be switched from IV to oral therapy at the same dose when clinically improved and able to tolerate an oral diet (Ref). The addition of metronidazole may not be necessary for uncomplicated biliary infection of mild to moderate severity (Ref). For acute diverticulitis, some experts suggest deferring antibiotics in otherwise healthy patients who are immunocompetent with mild disease (Ref).
Oral, IV: 500 mg every 8 to 12 hours as part of an appropriate combination regimen (Ref). Duration of therapy is 4 to 5 days following adequate source control (Ref). For diverticulitis or uncomplicated appendicitis managed without intervention, duration is 10 to 14 days (Ref); for perforated appendicitis managed with laparoscopic appendectomy, 2 to 4 days may be sufficient (Ref).
Intracranial abscess (brain abscess, intracranial epidural abscess) : IV: 7.5 mg/kg (usually 500 mg) every 6 to 8 hours (maximum dose: 4 g/day) for 6 to 8 weeks in combination with other appropriate antimicrobial therapy (Ref). Note: May switch IV metronidazole to oral metronidazole at the same dose to complete treatment course (Ref).
Odontogenic infection (off-label use):
Acute simple gingivitis, plaque-associated: Note: Reserve systemic therapy for patients with rapidly progressive disease, severe pain, or immunocompromising conditions (Ref).
Oral: 500 mg every 8 hours in combination with penicillin V for 5 to 7 days (Ref).
Periodontitis, severe, plaque-associated: Oral: 500 mg every 8 hours in combination with amoxicillin for 14 days or until clinical resolution; use in addition to periodontal debridement (Ref).
Pyogenic odontogenic soft tissue infection (alternative agent): IV, Oral: 500 mg every 8 hours as part of an appropriate combination regimen until resolution, typically for 7 to 14 days. Use in addition to appropriate surgical management (eg, drainage and/or extraction) (Ref).
Pneumonia, aspiration (alternative agent): Oral, IV: 500 mg 3 times daily in combination with an appropriate beta-lactam (eg, oral amoxicillin, IV penicillin, or an IV third-generation cephalosporin) for 7 days (Ref).
Sexually transmitted infections:
Empiric treatment following sexual assault in females (off-label use): Oral: 500 mg twice daily for 7 days, as part of an appropriate combination regimen (Ref).
Pelvic inflammatory disease: Oral, IV: 500 mg every 12 hours for 14 days as part of an appropriate combination regimen (Ref).
Trichomoniasis (index case and sex partner):
Initial treatment:
Females: Oral: 500 mg twice daily for 7 days. Note: Single 2 g dose is less effective (Ref), but some experts suggest it as an alternative for those unlikely to complete a multiday regimen (Ref).
Males: Oral: 2 g as a single dose (Ref). Note: Some experts suggest the multiday dosing used for females as an alternative regimen (Ref).
Refractory infection: Note: Patients with suspected reinfection because of reexposure to an untreated partner may receive a regimen used for initial treatment. For others, clinicians may request a kit from the CDC to perform drug-resistance testing (Ref).
Oral: 2 g once daily for 7 days. Alternatively, 500 mg twice daily for 7 days may be sufficient for patients with refractory infection following a single-dose regimen (Ref).
Skin and soft tissue infection:
Necrotizing infection (as a component of an appropriate combination regimen) (alternative agent): IV: 500 mg every 6 hours. Continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (Ref).
Surgical site infection, incisional (eg, intestinal or GU tract; axilla or perineum), warranting anaerobic coverage: IV: 500 mg every 8 hours in combination with other appropriate agents. Duration depends on severity, need for debridement, and clinical response (Ref).
Surgical prophylaxis:
IV: 500 mg within 60 minutes prior to surgical incision in combination with other antibiotics. Considered a recommended agent for select procedures involving the GI tract, urologic tract, or head and neck (Ref).
Oral:
Colorectal surgical prophylaxis (off-label use): 1 g every 3 to 4 hours for 3 doses with additional oral antibiotics, starting after mechanical bowel preparation the evening before a morning surgery and followed by an appropriate IV antibiotic prophylaxis regimen (Ref).
Uterine evacuation (induced abortion or pregnancy loss) (alternative agent) (off-label use): 500 mg as a single dose 1 hour prior to uterine aspiration; may be administered up to 12 hours before the procedure (Ref). Note: The optimal dosing regimen has not been established; various protocols are in use (Ref).
Tetanus ( Clostridium tetani infection) (off-label use): Oral, IV: 500 mg every 6 to 8 hours for 7 to 10 days in combination with supportive therapy (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Decreased kidney function does not impact serum half-life of metronidazole but is associated with accumulation of the active hydroxyl and almost inactive acetic acid metabolites (Ref). Kidney dysfunction may confer a higher risk of CNS side effects, such as neuropathy, encephalopathy, and seizures (Ref).
Note: Single-dose regimens (eg, 2 g once) do not require dose adjustment (Ref).
Altered kidney function:
IV, Oral:
CrCl ≥10 mL/minute: No dosage adjustment necessary (Ref); however, monitor closely for adverse effects due to accumulation of metabolites in patients with more severe impairment (CrCl <30 mL/minute), particularly with prolonged courses of therapy (Ref).
CrCl <10 mL/minute: No dosage adjustment necessary (Ref); however, monitor closely for adverse effects due to accumulation of metabolites, particularly with prolonged courses of therapy. A dose of 500 mg every 12 hours may be adequate to achieve therapeutic plasma levels for nonsevere non-Clostridioides difficile infections (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (42% to 65% metronidazole and hydroxyl and acetic acid metabolites (Ref)):
IV, Oral: Usual dose: 500 mg every 8 to 12 hours (Ref). Note: Larger doses may be utilized depending on clinical indication, but with close monitoring for adverse effects, particularly if the treatment course is >1 to 2 weeks in duration (Ref). On dialysis days, administer after dialysis. If administration cannot be separated from hemodialysis, consider supplemental dose following hemodialysis.
Peritoneal dialysis: Minimally dialyzed (10% removal with single long dwell (Ref)):
IV, Oral: No dosage adjustment necessary (Ref). Monitor for adverse effects due to metabolite accumulation, particularly if the treatment course is >1 to 2 weeks in duration (Ref).
CRRT:
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to metabolite accumulation is important:
IV, Oral: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration):
Note: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important:
IV, Oral: No dosage adjustment necessary (Ref). On PIRRT days, administer after PIRRT session. If administration cannot be separated from PIRRT, consider supplemental dose following completion of PIRRT session.
The liver dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Matt Harris, PharmD, MHS, BCPS, FAST, FCCP; Jeong Park, PharmD, MS, BCTXP, FCCP, FAST; Arun Jesudian, MD; Sasan Sakiani, MD.
Note: Metronidazole clearance is decreased and elimination half-life is prolonged in patients with cirrhosis (Ref). Prolonged use or total cumulative dose may result in accumulation that has been linked to neurotoxicity and encephalopathy, which may be irreversible (Ref). Metronidazole-induced encephalopathy can usually be confirmed (~90% of cases) through MRI (eg, T2 weighted/coronal fluid-attenuated inversion recovery sequences demonstrating symmetric lesions of the dendritic nuclei) (Ref). Close monitoring is warranted for early recognition of metronidazole-induced encephalopathy in patients with cirrhosis.
Liver impairment prior to treatment initiation: Single-dose regimens (eg, 2 g once) do not require dose adjustment (Ref).
Initial or dose adjustment in patients with preexisting liver cirrhosis:
Note: Single-dose regimens (eg, 2 g once) do not require dose adjustment (Ref).
Child-Turcotte-Pugh class A and B: No dosage adjustment necessary (Ref).
Child-Turcotte-Pugh class C: Oral, IV:
Capsules:
Amebiasis: 375 mg 3 times daily (Ref).
Trichomoniasis: 375 mg once daily (Ref).
Injection, tablets:
If usual recommended frequency is every 12 hours: No adjustment necessary.
If usual recommended frequency is every 6 to 8 hours: Maintain dose but reduce frequency to every 12 hours (Ref). For example, if usual recommended dose is 500 mg every 6 hours, then reduce to 500 mg every 12 hours.
Oral suspension: Reduce dose by 50% (Ref).
Severe cutaneous adverse reactions (eg, acute generalized exanthematous pustulosis, drug reactions with eosinophilia and systemic symptoms, Stevens-Johnson syndrome, toxic epidermal necrolysis): Discontinue metronidazole immediately and institute appropriate therapy.
Refer to adult dosing.
(For additional information see "Metronidazole (systemic): Pediatric drug information")
General dosing:
Infants, Children, and Adolescents:
Oral: 15 to 50 mg/kg/day in divided doses every 8 hours; maximum daily dose: 2,250 mg/day (Ref).
IV: 22.5 to 40 mg/kg/day in divided doses every 6 or 8 hours; maximum daily dose: 4,000 mg/day (Ref).
Amebiasis: Infants, Children, and Adolescents: Oral, IV: 35 to 50 mg/kg/day in divided doses every 8 hours for 7 to 10 days; maximum dose: 750 mg/dose; followed by an intraluminal agent (eg, paromomycin). Reserve IV therapy for severe infection or extraintestinal disease and switch to oral therapy when tolerated (Ref).
Balantidiasis: Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 5 days; maximum dose: 750 mg/dose (Ref).
Clostridioides difficile infection:
Infants: Oral, IV: 7.5 mg/kg/dose every 6 hours for 10 days; maximum dose: 500 mg/dose. If using for severe and complicated disease, use as part of an appropriate combination regimen (Ref).
Children and Adolescents:
Nonsevere infection, initial or first recurrence: Oral: 7.5 mg/kg/dose every 6 to 8 hours for 10 days; maximum dose: 500 mg/dose (Ref).
Severe/fulminant infection, initial: IV: 10 mg/kg/dose every 8 hours for 10 days; maximum dose: 500 mg/dose; use concomitantly with oral or rectal vancomycin (Ref).
Crohn disease, perianal disease; induction (adjunctive agent): Children and Adolescents: Oral: 20 to 30 mg/kg/day in divided doses every 8 to 12 hours as part of an appropriate combination regimen; maximum dose: 500 mg/dose. Reported duration variable; may be continued for ~4 to 12 weeks; overall duration of induction therapy dependent on clinical response (Ref).
Dientamoeba fragilis: Infants, Children, and Adolescents: Oral: 35 to 50 mg/kg/day in divided doses every 8 hours for 10 days; maximum dose: 750 mg/dose (Ref).
Exit-site or tunnel infection, peritoneal dialysis catheter: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose every 8 hours; maximum dose: 500 mg/dose (Ref).
Giardiasis: Infants, Children, and Adolescents: Oral: 5 mg/kg/dose every 8 hours for 5 to 7 days; maximum dose: 250 mg/dose (Ref).
Helicobacter pylori eradication: Limited data available: Note: Use as part of an appropriate combination regimen; usual duration of therapy is 14 days (Ref).
Weight-directed dosing: Children and Adolescents: Oral: 10 to 15 mg/kg/dose twice daily; maximum dose: 500 mg/dose (Ref).
Fixed dosing (Ref): Children and Adolescents:
15 to <25 kg: Oral: 250 mg twice daily.
25 to <35 kg: Oral: 500 mg in the morning and 250 mg in the evening or 375 mg twice daily (if using liquid preparation).
≥35 kg: Oral: 500 mg twice daily.
Intra-abdominal infection: Note: Use as part of an appropriate combination regimen. Treatment duration should be limited to 4 to 7 days after source control; longer durations are required when source control inadequate; in some circumstances (eg, acute appendicitis without perforation) therapy should be limited to ≤24 hours (Ref).
Divided dosing:
Infants <4 months: IV: 15 mg/kg loading dose once, followed 24 hours later by 7.5 mg/kg/dose every 6 hours (Ref).
Infants ≥4 months, Children, and Adolescents: IV: 30 to 40 mg/kg/day in divided doses every 8 hours; maximum dose: 500 mg/dose (Ref).
Once-daily dosing: Appendicitis: Children and Adolescents: IV: 30 mg/kg/dose every 24 hours; maximum dose: 1,500 mg/dose (Ref). For patients weighing <80 kg, some studies report a maximum dose of 1,000 mg/dose (Ref).
Pelvic inflammatory disease: Adolescents: Oral, IV: 500 mg every 12 hours for 14 days as part of an appropriate combination regimen (Ref).
Peritonitis in patients receiving peritoneal dialysis:
Prophylaxis: GI or GU procedures: Infants, Children, and Adolescents: IV: 10 mg/kg once prior to procedure in combination with cefazolin; maximum dose: 1,000 mg/dose (Ref).
Treatment: Infants, Children, and Adolescents: Oral: 10 mg/kg/dose every 8 hours; maximum dose: 400 mg/dose (Ref).
Sexually transmitted infections, empiric treatment following sexual assault in females: Adolescent females: Oral: 500 mg every 12 hours for 7 days as part of an appropriate combination regimen (Ref).
Small intestinal bacterial overgrowth: Very limited data available: Note: Optimal dosing regimen and duration of therapy are unknown; some prescribers report alternating courses of different antibiotics (Ref). Dosing based on small descriptive studies and published recommendations.
Children and Adolescents: Oral: Usual dose: 10 mg/kg/dose every 12 hours for 7 to 14 days. Maximum dose has not been established for this indication; however, a maximum of 500 mg/dose has been used for other indications. Reported range: 5 to 10 mg/kg/dose every 8 to 12 hours; may also consider guideline-recommended adult dose of 250 mg every 8 hours in appropriately sized patients (Ref).
Surgical prophylaxis: Children and Adolescents: IV: 15 mg/kg as a single dose 30 to 60 minutes prior to procedure; maximum dose: 500 mg/dose (Ref).
Surgical prophylaxis, colorectal: Children and Adolescents: Oral: 15 mg/kg/dose every 3 to 4 hours for 3 doses, starting after mechanical bowel preparation the afternoon and evening before the procedure, with or without additional oral antibiotics and with an appropriate IV antibiotic prophylaxis regimen; maximum dose: 1,000 mg/dose (Ref).
Tetanus (Clostridium tetani infection): Infants, Children, and Adolescents: IV, Oral: 30 mg/kg/day in divided doses every 8 hours for 7 to 10 days; maximum dose: 500 mg/dose (Ref).
Ulcerative colitis, pouchitis: Children and Adolescents: Oral: 20 to 30 mg/kg/day in divided doses every 8 hours for 14 days; maximum dose: 500 mg/dose (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Infants, Children, and Adolescents:
Manufacturer's labeling:
Mild, moderate, or severe impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, decreased renal function does not alter the single-dose pharmacokinetics.
ESRD requiring dialysis: Metronidazole metabolites may accumulate; monitor for adverse events; accumulated metabolites may be rapidly removed by dialysis.
Intermittent hemodialysis (IHD): If administration cannot be separated from hemodialysis, consider supplemental dose following hemodialysis.
Peritoneal dialysis (PD): No dosage adjustment necessary.
Alternate dosing: Others have used the following adjustments (Ref). Note: Renally adjusted dose recommendations are based on doses of 15 to 30 mg/kg/day divided every 6 to 8 hours.
GFR ≥10 mL/minute/1.73 m2: No adjustment required.
GFR <10 mL/minute/1.73 m2: 4 mg/kg/dose every 6 hours.
Intermittent hemodialysis (IHD): Extensively removed by hemodialysis: 4 mg/kg/dose every 6 hours.
Peritoneal dialysis (PD): Extensively removed by peritoneal dialysis: 4 mg/kg/dose every 6 hours.
Continuous renal replacement therapy (CRRT): No adjustment required.
Infants, Children, and Adolescents:
Mild or moderate impairment: No dosage adjustment necessary; use with caution and monitor for adverse events.
Severe impairment: Reduce dose by 50% (Ref). Based on experience in adult patients, the dosing interval may be prolonged while maintaining the usual individual dose (eg, administration of the usual dose but scheduling it every 12 hours instead of every 6) (Ref).
Metronidazole has been associated with a range of CNS effects, which include peripheral neuropathy (Ref), aseptic meningitis (Ref), ataxia (Ref), neuro cerebellar toxicity (Ref), confusion or disorientation (Ref), dysarthria (Ref), encephalopathy (Ref), seizures (Ref), optic neuropathy (Ref), and vertigo (Ref). Most reports have occurred in adults; however, there are reports in pediatric patients (Ref). CNS effects are generally reversible within days to weeks of discontinuation of therapy (Ref); however, some cases may not be reversible (Ref). Peripheral neuropathy symptoms may be prolonged after discontinuation.
Mechanism: Unclear; proposed mechanisms include binding to neural RNA inhibiting protein synthesis, modulation of inhibitory neurotransmitters gamma-aminobutyric acid receptors within the cerebellar and vestibular systems, reversible mitochondrial dysfunction, and vasogenic and cytotoxic edema (Ref).
Onset: Varied; median of 28 days was reported in a systematic review of metronidazole-induced encephalopathy (Ref) and a median of 54 days was reported in another systematic review (Ref); however, both reviews reported that some cases took less than a week.
Risk factors:
May include:
• High doses, high cumulative doses, or prolonged or repeated courses (Ref)
Limited cases of disulfiram-like reactions with metronidazole have been reported in both adult and pediatric patients when used concurrently with alcohol (Ref). Available clinical data demonstrating an association are conflicting and the CDC sexually transmitted infections guidelines state that refraining from alcohol use during metronidazole therapy is unnecessary (Ref). The proposed mechanism of disulfiram-like reactions is inhibition of aldehyde dehydrogenase, which results in the accumulation of aldehydes (Ref). In one case report, onset was rapid, occurring after 2 days (Ref). No risk factors have been identified.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea (10% to 12%)
Genitourinary: Vaginitis (15%)
Nervous system: Headache (18%)
1% to 10%:
Gastrointestinal: Abdominal pain (4%), diarrhea (4%), metallic taste (9%), xerostomia (2%)
Genitourinary: Dysmenorrhea (3%), genital pruritus (5%), urinary tract infection (2%), urine abnormality (3%)
Infection: Bacterial infection (7%), candidiasis (3%)
Nervous system: Dizziness (4%)
Respiratory: Flu-like symptoms (6%), pharyngitis (3%), rhinitis (4%), sinusitis (3%), upper respiratory tract infection (4%)
Frequency not defined:
Cardiovascular: Chest pain, flattened T-wave on ECG, flushing, palpitations, peripheral edema, syncope, tachycardia
Dermatologic: Erythematous rash, hyperhidrosis, pruritus, urticaria
Endocrine & metabolic: Decreased libido
Gastrointestinal: Abdominal cramps, anorexia, constipation, decreased appetite, dysgeusia, epigastric discomfort, glossitis, hairy tongue, proctitis, stomatitis, vomiting
Genitourinary: Cystitis, dyspareunia, dysuria, urinary incontinence, vaginal dryness, vulvovaginal candidiasis
Hematologic & oncologic: Agranulocytosis, eosinophilia
Hypersensitivity: Facial edema
Local: Inflammation at injection site, injection-site reaction
Nervous system: Asthenia, chills, depression, drowsiness, hypoesthesia, insomnia, irritability, malaise, numbness, psychosis
Neuromuscular & skeletal: Arthralgia, muscle spasm, myalgia
Ophthalmic: Abnormal eye movements (saccadic), nystagmus disorder
Renal: Polyuria
Respiratory: Dyspnea, nasal congestion
Miscellaneous: Fever
Postmarketing:
Cardiovascular: Prolonged QT interval on ECG (Ref)
Dermatologic: Acute generalized exanthematous pustulosis, bullous dermatitis, fixed drug eruption, Stevens-Johnson syndrome (Ref), toxic epidermal necrolysis (Ref)
Gastrointestinal: Pancreatitis (Ref)
Genitourinary: Urine discoloration (Ref)
Hematologic & oncologic: Leukopenia (Ref), neutropenia (Ref), thrombocytopenia (Ref)
Hepatic: Acute hepatic failure (especially in Cockayne syndrome) (Ref), hepatotoxicity (including severe hepatotoxicity, especially in Cockayne syndrome) (Ref)
Hypersensitivity: Anaphylaxis (Ref), drug reaction with eosinophilia and systemic symptoms, serum sickness-like reaction (joint pains) (Ref)
Nervous system: Aseptic meningitis (Ref), ataxia (Ref), confusion (Ref), dysarthria (Ref), encephalopathy (Ref), mania (Ref), neurocerebellar toxicity (Ref), paresthesia (Ref), peripheral neuropathy (Ref), seizure (Ref), vertigo (Ref)
Ophthalmic: Optic neuropathy (Ref)
Otic: Auditory impairment, hearing loss (including sensorineural hearing loss) (Ref), tinnitus
Miscellaneous: Disulfiram-like reaction (with alcohol) (Ref)
Hypersensitivity to metronidazole, nitroimidazole derivatives, or any component of the formulation; during the first trimester of pregnancy in patients with trichomoniasis (with the exception of Likmez); use of disulfiram within the past 2 weeks; use of alcohol or propylene glycol-containing products during therapy or within 3 days of therapy discontinuation; Cockayne syndrome.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Although the manufacturer’s labeling lists use of alcohol-containing products during therapy or within 3 days of therapy discontinuation as a contraindication, the CDC sexually transmitted infection guidelines state refraining from alcohol use while taking metronidazole is not necessary (CDC [Workowski 2021]). Clinical data demonstrating an association between concomitant use with alcohol and a disulfiram-like reaction are conflicting (Mergenhagen 2020).
Canadian labeling: Additional contraindications (not in the US labeling): Active neurological disorders; history of blood dyscrasia; hypothyroidism; hypoadrenalism.
Concerns related to adverse effects:
• Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with hepatic impairment due to potential accumulation; dosage adjustment recommended in patients with severe hepatic impairment.
• Renal impairment: Use with caution in patients with renal impairment due to potential accumulation; dosage adjustments may be required.
• Seizure disorder: Use with caution in patients with a history of seizure disorder.
Dosage-form specific issues:
• Injection: Use injection with caution in patients with heart failure, edema, or other sodium-retaining states, including corticosteroid treatment due to high sodium content. In patients receiving continuous nasogastric secretion aspiration, sufficient metronidazole may be removed in the aspirate to cause a reduction in serum levels.
Parenteral solution contains 28 mEq of sodium/gram of metronidazole.
First-Metronidazole oral suspension is a compounding kit. Refer to manufacturer's labeling for compounding instructions.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Flagyl: 375 mg [DSC]
Generic: 375 mg
Solution, Intravenous:
Generic: 500 mg (100 mL); 500 mg/100 mL (100 mL)
Solution, Intravenous [preservative free]:
Generic: 500 mg (100 mL); 500 mg/100 mL (100 mL)
Suspension, Oral:
Likmez: 500 mg/5 mL (75 mL) [contains methylparaben, propylparaben]
Likmez: 500 mg/5 mL (200 mL) [contains methylparaben, propylparaben; strawberry peppermint flavor]
Tablet, Oral:
Generic: 125 mg, 250 mg, 500 mg
May be product dependent
Capsules (metroNIDAZOLE Oral)
375 mg (per each): $12.29
Solution (metroNIDAZOLE Intravenous)
500 mg/100 mL (per mL): $0.01 - $0.04
Suspension (Likmez Oral)
500 mg/5 mL (per mL): $3.27
Tablets (metroNIDAZOLE Oral)
125 mg (per each): $16.59
250 mg (per each): $0.43 - $0.48
500 mg (per each): $0.73 - $0.84
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Flagyl: 500 mg [DSC] [contains fd&c blue #1 (brilliant blue), quinoline yellow (d&c yellow #10)]
Generic: 500 mg
Solution, Intravenous:
Generic: 500 mg/100 mL (100 mL)
Tablet, Oral:
Generic: 250 mg
IV: Infuse intravenously over 30 to 60 minutes. Avoid contact of drug solution with equipment containing aluminum.
Oral: Administer with food to minimize stomach upset. Shake suspension well before use; administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose.
Oral: May administer with food to minimize GI upset.
Suspension: Shake well before use. Administer with an accurate measuring device (calibrated oral syringe or measuring cup); do not use a household teaspoon or tablespoon to measure dose.
Parenteral: IV: Administer undiluted (5 mg/mL) by slow intermittent infusion over 30 to 60 minutes. Avoid contact of drug solution with equipment containing aluminum.
Amebiasis: Treatment of acute intestinal amebiasis (amebic dysentery) and extraintestinal amebiasis (liver abscess).
Limitations of use: When used for amebic liver abscess, may be used concurrently with percutaneous needle aspiration when clinically indicated.
Anaerobic bacterial infections (caused by Bacteroides spp. , including the B. fragilis group):
Bone and joint infections: Treatment (adjunctive therapy) of bone and joint infections.
CNS Infections: Treatment of CNS infections, including meningitis and brain abscess.
Endocarditis: Treatment of endocarditis.
Gynecologic infections: Treatment of gynecologic infections including endometritis, endomyometritis, tubo-ovarian abscess, and postsurgical vaginal cuff infection (also caused by Clostridium spp., Peptococcus spp., Peptostreptococcus spp., and Fusobacterium spp.).
Intra-abdominal infections: Treatment of intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess (also caused by Clostridium spp., Eubacterium spp., Peptococcus spp., and Peptostreptococcus spp.).
Lower respiratory tract infections: Treatment of lower respiratory tract infections, including pneumonia, empyema, and lung abscess.
Sepsis: Treatment of sepsis including bloodstream infection (also caused by Clostridium spp.).
Skin and skin structure infections: Treatment of skin and skin structure infections (also caused by Clostridium spp., Peptococcus spp., Peptostreptococcus spp., and Fusobacterium spp.).
Surgical prophylaxis (colorectal surgery): Injection: Preoperative, intraoperative, and postoperative prophylaxis to reduce the incidence of postoperative infection in patients undergoing elective colorectal surgery classified as contaminated or potentially contaminated.
Trichomoniasis: Treatment of infections caused by Trichomonas vaginalis, including treatment of asymptomatic sexual partners.
Balantidiasis; Bite wound infection, prophylaxis or treatment (animal or human bite); Clostridioides difficile infection, treatment; Crohn disease; Dientamoeba fragilis infection; Empiric treatment (of sexually transmitted infections) in females following sexual assault; Giardiasis; Helicobacter pylori eradication; Odontogenic infection; Pouchitis (post ileal pouch-anal anastomosis), acute; Surgical prophylaxis, colorectal surgery (oral metronidazole); Surgical prophylaxis, uterine evacuation (induced abortion or pregnancy loss); Tetanus
MetroNIDAZOLE may be confused with mebendazole, meropenem, metFORMIN, methotrexate, metoclopramide, miconazole.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs (contraindicated in pregnancy [first trimester in patients with trichomoniasis, except Likmez]; pediatric liquid medications requiring measurement) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Community/Ambulatory Care Settings).
Substrate of CYP2A6 (Major with inducers), CYP2A6 (Minor with inhibitors); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits CYP2C9 (Weak);
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Alcohol (Ethyl): MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Alcohol (Ethyl). A disulfiram-like reaction may occur. Risk X: Avoid
Bacillus clausii: Antibiotics may decrease therapeutic effects of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider Therapy Modification
BCG (Intravesical): Antibiotics may decrease therapeutic effects of BCG (Intravesical). Risk X: Avoid
BCG Vaccine (Immunization): Antibiotics may decrease therapeutic effects of BCG Vaccine (Immunization). Risk C: Monitor
Busulfan: MetroNIDAZOLE (Systemic) may increase serum concentration of Busulfan. Management: Avoid coadministration metronidazole and busulfan due to increased risks of busulfan toxicity. If coadministration is required, monitor busulfan concentrations closely and adjust the busulfan dose as needed. Risk D: Consider Therapy Modification
Cholera Vaccine: Antibiotics may decrease therapeutic effects of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid
Disulfiram: May increase adverse/toxic effects of MetroNIDAZOLE (Systemic). In particular, the risk for CNS toxicities such as psychosis may be increased. Risk X: Avoid
DroNABinol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of DroNABinol. Specifically, metronidazole may produce severe intolerance to the alcohol contained in the dronabinol oral solution. Risk X: Avoid
Fecal Microbiota (Live) (Oral): May decrease therapeutic effects of Antibiotics. Risk X: Avoid
Fecal Microbiota (Live) (Rectal): Antibiotics may decrease therapeutic effects of Fecal Microbiota (Live) (Rectal). Risk X: Avoid
Fluorouracil Products: MetroNIDAZOLE (Systemic) may increase serum concentration of Fluorouracil Products. Risk C: Monitor
Fosphenytoin: May decrease serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase serum concentration of Fosphenytoin. Risk C: Monitor
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of Haloperidol. Risk C: Monitor
Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies): Antibiotics may decrease therapeutic effects of Immune Checkpoint Inhibitors (Anti-PD-1, -PD-L1, and -CTLA4 Therapies). Risk C: Monitor
Lactobacillus and Estriol: Antibiotics may decrease therapeutic effects of Lactobacillus and Estriol. Risk C: Monitor
Lithium: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Lithium. MetroNIDAZOLE (Systemic) may increase serum concentration of Lithium. Risk C: Monitor
Mebendazole: May increase adverse/toxic effects of MetroNIDAZOLE (Systemic). Particularly the risk for Stevens-Johnson syndrome or toxic epidermal necrolysis may be increased. Risk X: Avoid
Mycophenolate: Antibiotics may decrease active metabolite exposure of Mycophenolate. Specifically, concentrations of mycophenolic acid (MPA) may be reduced. Risk C: Monitor
PHENobarbital: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of PHENobarbital. A disulfiram-like reaction may occur if combined with phenobarbital dosage forms that contain propylene glycol or alcohol. PHENobarbital may decrease serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor
Phenytoin: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Phenytoin. A disulfiram-like reaction may occur if combined with phenytoin dosage forms that contain propylene glycol. Phenytoin may decrease serum concentration of MetroNIDAZOLE (Systemic). MetroNIDAZOLE (Systemic) may increase serum concentration of Phenytoin. Risk C: Monitor
Primidone: May decrease serum concentration of MetroNIDAZOLE (Systemic). Risk C: Monitor
Products Containing Ethanol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Products Containing Ethanol. A disulfiram-like reaction may occur. Risk X: Avoid
Products Containing Propylene Glycol: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Products Containing Propylene Glycol. A disulfiram-like reaction may occur. Risk X: Avoid
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Sodium Picosulfate: Antibiotics may decrease therapeutic effects of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider Therapy Modification
Sulfonylureas: MetroNIDAZOLE (Systemic) may increase serum concentration of Sulfonylureas. Risk C: Monitor
Tipranavir: MetroNIDAZOLE (Systemic) may increase adverse/toxic effects of Tipranavir. A disulfiram-like reaction may occur due to the alcohol contained in tipranavir capsules. Risk C: Monitor
TOLBUTamide: CYP2C9 Inhibitors (Weak) may increase serum concentration of TOLBUTamide. Risk C: Monitor
Typhoid Vaccine: Antibiotics may decrease therapeutic effects of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider Therapy Modification
Vecuronium: MetroNIDAZOLE (Systemic) may increase neuromuscular-blocking effects of Vecuronium. Risk C: Monitor
Vitamin K Antagonists: MetroNIDAZOLE (Systemic) may increase serum concentration of Vitamin K Antagonists. Management: Consider alternatives to concomitant therapy with these agents. If concomitant therapy cannot be avoided, consider reducing the dose of the vitamin K antagonist and monitor for increased INR/bleeding. Risk D: Consider Therapy Modification
Peak antibiotic serum concentration lowered and delayed, but total drug absorbed not affected.
Metronidazole crosses the placenta.
Cleft lip with or without cleft palate has been reported following first trimester exposure to metronidazole; however, most studies have not shown an increased risk of congenital anomalies or other adverse events to the fetus following maternal use during pregnancy. Because metronidazole was carcinogenic in some animal species, concern has been raised whether metronidazole should be used during pregnancy. Available studies have not shown an increased risk of infant cancer following metronidazole exposure during pregnancy; however, the ability to detect a signal for this may have been limited.
Metronidazole pharmacokinetics are similar between pregnant and nonpregnant patients (Amon 1981; Visser 1984; Wang 2011).
Bacterial vaginosis and vaginal trichomoniasis are associated with adverse pregnancy outcomes (such as premature rupture of membranes, preterm delivery). The CDC recommends treatment of pregnant patients with symptomatic bacterial vaginosis; the twice daily dose of oral metronidazole for the treatment of bacterial vaginosis is the same for nonpregnant and pregnant patients; however, a three times daily regimen has also been used. Treatment of pregnant patients with asymptomatic bacterial vaginitis who are at high risk for preterm delivery has had mixed results. Metronidazole is also recommended for the treatment of vaginal trichomoniasis in pregnant patients. Although use of oral metronidazole for vaginal trichomoniasis during the first trimester is contraindicated by the manufacturer, available guidelines note treatment can be given at any stage of pregnancy (CDC [Workowski 2021]).
Metronidazole may also be used for the treatment of giardiasis in pregnant patients (some sources recommend second and third trimester administration only) (Gardner 2001; HHS [OI adult 2020]) and symptomatic amebiasis during pregnancy (HHS [OI adult 2020]; Li 1996). Short courses may be used for the treatment of pouchitis or perianal disease in pregnant patients with inflammatory bowel disease; not recommended for planned maintenance therapy (Mahadevan 2019). The use of other agents is preferred when treatment is needed for Clostridioides difficile during pregnancy (ACG [Kelly 2021]). Consult current recommendations for appropriate use in pregnant patients.
Metronidazole and its active hydroxyl metabolite are present in breast milk at concentrations similar to maternal plasma concentrations.
Data related to the presence of metronidazole in breast milk are available from multiple studies:
• Metronidazole transfer to breast milk was assessed in 3 women 6, 13, and 14 weeks' postpartum. Metronidazole 2 g was given orally as a single dose. Breastfeeding was withheld for 24 hours after the dose and several milk samples were collected during these 24 hours. The highest average milk concentrations occurred 2 to 4 hours after the dose; the highest reported average milk concentration was 45.8 mcg/mL. Average milk concentrations were ~12.6 mcg/mL 12 to 24 hours after the dose. The half-life of metronidazole in breast milk was ~9 to 10 hours (2 patients). The authors estimated the infant dose received via breast milk to be 21.8 mg in the first 24 hours and an additional 3.5 mg in the second day after the dose. They noted that withholding breastfeeding for 12 to 24 hours would significantly decrease metronidazole exposure to the breastfeeding infant (Erickson 1981). Metabolite concentrations were not measured in this study. The relative infant dose (RID) of metronidazole is 13.7% to 22.9% when calculated using the highest average breast milk concentration reported in the study (45.8 mcg/mL), compared to an oral infant therapeutic dose of 30 to 50 mg/kg/day, providing an estimated daily infant dose via breast milk of 6.87 mg/kg/day.
• A review article used information from 4 published studies to calculate an RID for metronidazole and compare it to other antibiotics. Maternal doses of oral metronidazole used in these studies ranged from 200 to 400 mg 3 times daily (Heisterberg 1983; Passmore 1988; Willis 1978) or a 2 g single oral dose (Erickson 1981). Authors of the review calculated the RID of metronidazole to be 11%, providing a median estimated daily infant dose via breast milk of 1.59 mg/kg/day (van Wattum 2019).
• In general, breastfeeding is considered acceptable when the RID is <10%; when an RID is >25%, breastfeeding should generally be avoided (Anderson 2016; Ito 2000). Additional considerations can include the gestational and postnatal age of the infant, the actual amount of milk being ingested (less in the first couple days of life and when weaning), properties of the specific maternal medication, medical conditions of the infant, and medications the infant is receiving therapeutically.
• Breast milk was also evaluated following administration of metronidazole 500 mg IV 3 times a day for 2 days to patients following cesarean delivery. Sampling occurred 1 to 2 hours after the dose on the second day of therapy. Metronidazole concentrations were 7.3 to 10.1 mcg/mL (breast milk) and 7.7 to 13.1 mcg/mL (maternal plasma) (Geballa-Koukoula 2018).
Loose stools, oral and perianal Candida growth, and oral thrush have been reported in breastfeeding infants exposed to metronidazole (Passmore 1988).
Metronidazole and its active metabolite can be detected in the serum of breastfeeding infants (Gray 1961; Heisterberg 1983; Passmore 1988).
A potential for tumorigenicity was observed following chronic oral doses in animal studies; the clinical relevance of this is unclear. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother. Alternately, the mother can express and discard milk for 48 hours after the last dose and feed the infant stored human milk or formula.
Some guidelines note if metronidazole is given, breastfeeding should be withheld for 12 to 24 hours after a single 2 g dose (CDC [Workowski 2021]; WHO 2002); alternatively, the mother may pump and discard breast milk for 24 hours after taking the last metronidazole dose. Use of lower maternal doses may provide lower concentrations of metronidazole in breast milk and use can be considered in patients who are breastfeeding (CDC [Workowski 2021]). Use of other agents is preferred when treating breastfeeding patients for diseases such as Clostridioides difficile infection, or pouchitis or perianal disease in lactating patients with inflammatory bowel disease (ACG [Kelly 2021]).
Take with food to minimize stomach upset.
Sodium: Injectable dosage form may contain sodium.
Ethanol: According to the manufacturer’s labeling, use of ethanol is contraindicated during therapy and for 3 days after therapy discontinuation; however, the CDC sexually transmitted infection guidelines state refraining from alcohol use while taking metronidazole is not necessary (CDC [Workowski 2021]). Clinical data demonstrating an association between concomitant use with alcohol and a disulfiram-like reaction are conflicting (Mergenhagen 2020).
Monitor CBC with differential at baseline, during, and after prolonged or repeated courses of therapy. Closely monitor older patients and patients with severe hepatic impairment or ESRD for adverse reactions. Neurologic symptoms; observe patients carefully if neurologic symptoms occur and consider discontinuation of therapy. Signs and symptoms of severe cutaneous adverse reactions.
After diffusing into the organism, interacts with DNA to cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis and cell death in susceptible organisms
Absorption: Oral: Well absorbed.
Distribution: To bile, seminal fluid, bone, liver, and liver abscesses, lung and vaginal secretions; crosses blood-brain barrier; saliva and CSF concentrations similar to those in plasma.
Vd:
Preterm neonates (PMA: 24 to 39 weeks): Median: 0.95 L/kg (range: 0.75 to 1.03 L/kg) (Cohen-Wolkowiez 2013).
Children ≥9 years and Adolescents ≤14 years: 0.64 ± 0.18 L/kg (Amon 1983).
Protein binding: <20%.
Metabolism: Hepatic (30% to 60%) to several metabolites including an active hydroxyl metabolite which maintains activity ~30% to 65% of the parent compound (Lamp 1999).
Half-life elimination:
Neonates <7 days (Jager-Roman 1982): Within first week of life, more prolonged with lower GA:
GA 28 to 30 weeks: 75.3 ± 16.9 hours.
GA 32 to 35 weeks: 35.4 ± 1.5 hours.
GA 36 to 40 weeks: 24.8 ± 1.6 hours.
Neonates ≥7 days: ~22.5 hours (Upadhyaya 1988).
Children and Adolescents: 6 to 10 hours (Lamp 1999).
Adults: ~8 hours.
Time to peak, serum: Oral: Capsules, tablets: 1 to 2 hours; oral suspension: 0.25 to 6 hours.
Excretion: Urine (unchanged drug and metabolites: 60% to 80%; ~20% of total as unchanged drug); feces (6% to 15%).
Altered kidney function: CrCl ≤65 mL/minute: Half-life: 18 to 32 hours (hydroxy metabolite [active]) (Lamp 1999).
Hepatic function impairment: Half-life: 18.31 hours (mean) in one study (Lau 1987).
According to Child-Pugh classification (Muscara 1995):
Child-Pugh class A: ~10.7 hours.
Child-Pugh class B: ~13.5 hours.
Child-Pugh class C: ~21.5 hours.
Anti-infective considerations:
Parameters associated with efficacy: Concentration dependent; associated with total AUC24/minimum inhibitory concentration (MIC) (Craig 1998; Ibrahim 2004).
Organism specific: B. fragilis: Goal: AUC/MIC ≥70 (Sprandel 2006).
Expected drug exposure in normal renal function:
Cmax (peak): Single dose:
Neonates and Infants <8 weeks PNA: IV: 20 mg/kg: 17.7 ± 3.1 mg/L (Rubenson 1986).
Infants 3 to 10 months of age: IV: 20 mg/kg: 25.3 ± 4.5 mg/L (Rubenson 1986).
Children ≥4 years of age and Adolescents ≤17 years of age: IV: 30 mg/kg (maximum dose: Weight <80 kg: 1,000 mg; Weight >80 kg: 1,500 mg): ~50 mg/L (Child 2019).
Adults: Oral:
250 mg: 6 mg/L (manufacturer's labeling).
500 mg: ~8 to 12 mg/L (Lamp 1999; manufacturer's labeling).
2 g: 40 mg/L (manufacturer’s labeling).
Cmax (peak): Steady state:
Preterm Neonates (GA ≤32 weeks; PNA ≤90 days): IV: 15 mg/kg loading dose followed by 7.5 mg/kg every 12 hours (PNA <14 days) or 24 hours (PNA ≥14 days): 24.6 mg/L (Cohen-Wolkowiez 2013).
Adults: IV:
500 mg every 8 hours: 22.2 ± 5 mg/L (Sprandel 2004).
1 g once daily: 24.8 ± 6.8 mg/L (Sprandel 2004).
1.5 g once daily: 37.7 ± 10 mg/L (Sprandel 2004).
15 mg/kg loading dose; 7.5 mg/kg every 6 hours: 25 mg/L (manufacturer’s labeling).
AUC0-24 (total): Single dose:
Children ≥4 years of age and Adolescents ≤17 years of age (Child 2019): IV: 30 mg/kg (maximum dose: Weight <80 kg: 1,000 mg; Weight >80 kg: 1,500 mg):
4 to 5 years of age: 612 to 732 mg•hour/L.
6 to 9 years of age: 520 to 588 mg•hour/L.
10 to 12 years of age: 419 to 478 mg•hour/L.
13 to 17 years of age: 313 to 369 mg•hour/L.
AUC0-24 (total): Steady state:
Adults: IV:
500 mg every 8 hours: 356 ± 68 mg•hour/L (Sprandel 2004).
1 g once daily: 227 ± 57 mg•hour/L (Sprandel 2004).
1.5 g once daily: 338 ± 105 mg•hour/L (Sprandel 2004).
Postantibiotic effect: Varies based on the organism and antimicrobial exposure (concentration and duration):
C. difficile: 1.2 to 1.7 hours (Odenholt 2007).
T. vaginalis: ~6 hours (Nix 1995).
