METRONIDAZOLE
Clinical safety rating: safe
Disulfiram-like reaction can occur with alcohol Can cause peripheral neuropathy and seizures with prolonged use.
After entry into the cell, metronidazole is reduced by bacterial nitroreductases to form toxic metabolites that damage DNA and inhibit nucleic acid synthesis, leading to cell death.
| Metabolism | Hepatic metabolism via oxidation and glucuronidation; major cytochrome P450 enzymes: CYP2A6, CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1; also reduced by nitroreductases in some bacteria and human cells. |
| Excretion | Renal (60-80% unchanged drug), biliary/fecal (6-15% as metabolites, <20% unchanged). |
| Half-life | 8 hours (range 6-10 hours) in adults; prolonged to 18-20 hours in severe hepatic impairment; requires adjustment in cirrhosis. |
| Protein binding | <20% bound to plasma proteins (albumin). |
| Volume of Distribution | 0.7-1.1 L/kg; Vd increased in edema/ascites; distributes widely including CNS, bone, and abscess cavities. |
| Bioavailability | Oral: 80-95% (100% for immediate-release); Topical: <2% systemic; Vaginal: 20-25% systemic after 500 mg dose. |
| Onset of Action | Oral: 1-2 hours; IV: immediate; Topical: 2-6 hours; Vaginal: 24-72 hours for trichomoniasis. |
| Duration of Action | Oral/IV: 12-24 hours; Topical: 8-12 hours; Vaginal: 24-72 hours. Metronidazole is bactericidal for 12-24 hours post-dose. |
| Molecular Weight | 171.15 |
500 mg intravenously every 8 hours or 500 mg orally every 8 hours; for bacterial vaginosis, 500 mg orally twice daily for 7 days; for trichomoniasis, 2 g orally as a single dose.
| Dosage form | GEL |
| Renal impairment | For GFR 10-50 mL/min: no adjustment needed; for GFR <10 mL/min: extend interval to every 12 hours if using multiple doses; for intermittent hemodialysis: administer dose after dialysis on dialysis days. |
| Liver impairment | For Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: use with caution, consider further dose reduction (e.g., 50% of normal dose every 12 hours) and monitor for toxicity. |
| Pediatric use | Neonates: 15 mg/kg loading dose, then 7.5 mg/kg every 12 hours for <7 days, or every 8 hours for 7-28 days; Infants and children: 7.5 mg/kg every 6 hours (max 4 g/day) for most infections; for amebiasis: 35-50 mg/kg/day in 3 divided doses for 10 days. |
| Geriatric use | No specific dose adjustment based solely on age, but monitor renal function; reduce dose if creatinine clearance <10 mL/min as per renal adjustment; use lowest effective dose and monitor for neurotoxicity (e.g., peripheral neuropathy, seizures). |
| 1st trimester | Contraindicated due to possible teratogenic effects (cleft palate, CNS defects) based on animal data; use only if no alternative. |
| 2nd trimester | Use only if clearly needed; crosses placenta; associated with potential for carcinogenicity in animal studies. |
| 3rd trimester | Generally avoided due to possible carcinogenic risk; use only if benefit outweighs risk, especially near term. |
Clinical note
Disulfiram-like reaction can occur with alcohol Can cause peripheral neuropathy and seizures with prolonged use.
| FDA category | Human |
| Placental transfer | Crosses the placenta readily; fetal concentrations similar to maternal levels. |
| Breastfeeding |
■ FDA Black Box Warning
Carcinogenicity has been observed in mice and rats following chronic administration; however, the relevance to humans is unclear.
| Common Effects | protozoal infections |
| Serious Effects |
Hypersensitivity to metronidazole or other nitroimidazole derivativesPregnancy (first trimester) for systemic useCockayne syndrome (case reports of severe hepatotoxicity)
| Precautions | May cause peripheral neuropathy and CNS effects including seizures, dizziness, and ataxia; discontinue if abnormal neurologic signs occur., Carcinogenicity in animal studies; use for shortest duration necessary., Hepatotoxicity and pancreatitis reported., Hypersensitivity reactions including Stevens-Johnson syndrome., May prolong QT interval; use with caution in patients with electrolyte disturbances or taking other QT-prolonging drugs., Potential for disulfiram-like reaction with alcohol; avoid during therapy and for at least 48 hours after completion., Possible mutagenicity; avoid use in pregnancy (especially first trimester) unless clearly needed., May cause metallic taste, nausea, and other GI disturbances. |
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| Enters breast milk in significant amounts; may cause diarrhea, rash, or bitter taste in infant; avoid breastfeeding during therapy or withhold for 12-24 hours after last dose. |
| Lactation Rating | L4 |
| Teratogenic Risk | Metronidazole crosses the placenta. First trimester: limited human data show no consistent increase in major malformations; however, some studies suggest a possible small risk of oral clefts. Second/third trimester: generally considered low risk; no known fetal toxicity at standard doses. Avoid high doses in first trimester unless essential. |
| Fetal Monitoring | Monitor maternal liver function, complete blood count (CBC) with differential during prolonged therapy. Fetal: no specific fetal monitoring required for standard short-term use; in high-dose or IV therapy, consider fetal heart rate monitoring in third trimester for preterm labor risk. |
| Fertility Effects | Metronidazole has no known significant effects on human fertility. Animal studies show no impairment of fertility at therapeutic doses. |
| Food/Dietary | Avoid alcohol and alcohol-containing foods (e.g., sauces, vinegars, some desserts) during therapy and for 48 hours after completion. No other significant food interactions. |
| Clinical Pearls | Metronidazole is a nitroimidazole antibiotic effective against anaerobic bacteria and protozoa. It requires acidic environment for activation; thus, avoid concurrent use with antacids or H2 blockers. Monitor for peripheral neuropathy and seizure with prolonged use. Disulfiram-like reaction occurs with alcohol; counsel patients to avoid alcohol during therapy and for 48 hours after last dose. Use caution in hepatic impairment (dose reduction recommended). Intravenous form is irritant; do not co-administer with blood products via same line. |
| Patient Advice | Avoid alcohol and alcohol-containing products during treatment and for 48 hours after the last dose to prevent severe nausea, vomiting, and flushing. · Take with food to minimize gastrointestinal upset. · Complete the full course even if symptoms improve. · Report numbness, tingling, or seizures immediately. · May cause metallic taste (harmless) and darkening of urine (not clinically significant). |