FLAGYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for FLAGYL (FLAGYL).
Metronidazole, a nitroimidazole antibiotic, enters bacterial cells and is reduced to cytotoxic intermediates that damage DNA and inhibit nucleic acid synthesis, leading to cell death. It is active against anaerobic bacteria and protozoa.
| Metabolism | Hepatic metabolism via oxidation and glucuronidation; major metabolites include hydroxy metabolite (active) and acid metabolite. CYP450 enzymes involved (CYP2A6, CYP2C9, CYP3A4). |
| Excretion | Renal: 60-80% of dose excreted unchanged in urine; biliary/fecal: 6-15% as metabolites and unchanged drug; enterohepatic circulation contributes to prolonged elimination. |
| Half-life | Terminal elimination half-life: 6-8 hours in adults with normal renal function; prolonged to 7-21 hours in hepatic impairment; no significant change in renal impairment; clinically relevant for dosing interval (usually 8-hourly). |
| Protein binding | Less than 20% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Volume of distribution: 0.6-0.8 L/kg (approximately 40-60 L in adults), indicating extensive tissue penetration; exceeds total body water, consistent with distribution into all tissues including abscess cavities and CNS. |
| Bioavailability | Oral bioavailability: 80-100% (well absorbed); IV bioavailability: 100% (by definition); Topical: Systemic absorption minimal (<2%). |
| Onset of Action | Oral: Onset of clinical effect within 1-2 hours after dose; IV: Immediate after infusion, with therapeutic concentrations achieved within 30 minutes; Topical: Clinical response may take 2-5 days. |
| Duration of Action | Duration: Approximately 12-24 hours after a single dose, depending on dose and route; clinical effects persist for 8-12 hours for infections due to sustained tissue levels. |
| Molecular Weight | 171.15 |
| Action Class | 5-Nitroimidazole (Antiprotozoal & Antibacterial) |
| Brand Substitutes | Metrogyl Suspension |
Metronidazole 500 mg intravenously every 8 hours or 500 mg orally every 8 hours.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >10 mL/min). For severe renal impairment (GFR <10 mL/min), reduce dose to 500 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce dose by 50% (e.g., 250 mg every 8 hours). Child-Pugh C: reduce dose to 250 mg every 12 hours. |
| Pediatric use | 15-50 mg/kg/day intravenously or orally divided every 8 hours, depending on infection type and severity. Maximum 4 g/day. |
| Geriatric use | Monitor renal function; same dosing as adults unless severe renal impairment (CrCl <10 mL/min) requires dose reduction to 500 mg every 12 hours. |
| 1st trimester | Avoid unless clearly needed; associated with cleft palate in animal studies and possible carcinogenicity. Use only if no alternative. |
| 2nd trimester | Use only if clearly needed; consider lowest effective dose for shortest duration. Known to cross placenta. |
| 3rd trimester | Use only if clearly needed; avoid high doses near term due to potential accumulation and unknown fetal effects. |
Clinical note
Comprehensive clinical and safety monograph for FLAGYL (FLAGYL).
| Placental transfer | Readily crosses placenta; fetal concentrations comparable to maternal serum levels. |
| Breastfeeding | Metronidazole is excreted into breast milk in significant amounts (up to 10% of maternal dose). After a single 2g dose, withhold breastfeeding for 12-24 hours. For chronic therapy, alternative agents are preferred due to potential carcinogenicity and mutagenicity. |
■ FDA Black Box Warning
Carcinogenicity: Metronidazole has been shown to be carcinogenic in mice and rats. Chromosomal aberrations have been reported in patients with Crohn's disease and other conditions. Use should be reserved for approved indications only.
| Serious Effects |
Hypersensitivity to metronidazole or other nitroimidazole derivativesFirst trimester of pregnancy (relative, but often considered absolute by some guidelines)
| Precautions | Carcinogenicity risk (see black box warning), Neurologic effects: peripheral neuropathy, seizures, encephalopathy; discontinue if abnormal neurologic signs occur, Hematologic effects: leukopenia, neutropenia; monitor CBC, Hepatic impairment: dosage adjustment recommended, Metronidazole may cause metallic taste, dark urine, and disulfiram-like reaction with alcohol, Prolonged use may result in superinfection (e.g., C. difficile diarrhea), Potential for ethylene glycol toxicity if administered with propylene glycol-containing solutions |
| Food/Dietary | Avoid alcohol and any products containing ethanol (including certain mouthwashes, cough syrups, and fermented foods) during therapy and for at least 48 hours after last dose. No other food restrictions. |
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| Lactation Rating | L3 (Moderately Safe) - Use with caution; consider temporary cessation of breastfeeding after high doses. |
| Teratogenic Risk | Flagyl (metronidazole) crosses the placenta. In the first trimester, use is generally avoided due to theoretical risk of teratogenicity, but data from large cohort studies do not show a significant increase in major malformations (risk category B). In the second and third trimesters, no fetal harm has been demonstrated; however, use only if clearly needed. High doses associated with fetal toxicity in animals. |
| Fetal Monitoring | Monitor maternal liver function (AST, ALT) due to rare hepatotoxicity; complete blood count if therapy exceeds 10 days. Fetal monitoring with ultrasound if used in pregnancy for prolonged courses. No specific fetal monitoring required for short-term use. |
| Fertility Effects | No known adverse effects on fertility in humans. In animal studies, no impairment of fertility at therapeutic doses. |
| Clinical Pearls | Flagyl (metronidazole) is first-line for anaerobic infections and bacterial vaginosis. It can cause a disulfiram-like reaction with alcohol; avoid ethanol during therapy and for 48 hours after last dose. Monitor for peripheral neuropathy with prolonged use. IV formulation is highly irritating; avoid extravasation. Use with caution in hepatic impairment; dose reduction may be needed. Metallic taste is common but benign. |
| Patient Advice | Do not drink alcohol or use products containing alcohol during treatment and for 48 hours after the last dose to avoid severe nausea, vomiting, and flushing. · Take with food to reduce gastrointestinal upset. · Complete the full course even if symptoms improve to prevent resistance. · May cause a metallic taste, which is temporary. · Avoid sexual intercourse or use condoms during treatment for trichomoniasis; partners may need treatment. · Notify doctor if you experience numbness, tingling, or pain in hands/feet. · For vaginal gel, avoid alcohol-containing products (e.g., douches) for 24 hours after use. |