METRONIDAZOLE HYDROCHLORIDE
Clinical safety rating: safe
Disulfiram-like reaction can occur with alcohol Can cause peripheral neuropathy and seizures with prolonged use.
Upon anaerobic reduction of the nitro group, forms toxic intermediates that damage bacterial DNA and inhibit nucleic acid synthesis.
| Metabolism | Hepatic metabolism via oxidation (CYP450 enzymes) and glucuronidation; major metabolites include hydroxy-metronidazole (active). |
| Excretion | Renal 60-80% as unchanged drug and metabolites; fecal 6-15%; biliary minor. |
| Half-life | 7-8 hours in healthy adults; prolonged to 20-30 hours in severe hepatic impairment. |
| Protein binding | <20% bound to plasma proteins. |
| Volume of Distribution | 0.6-1.1 L/kg; wide distribution including CNS, abscesses, and bone. |
| Bioavailability | Oral: 80-100%; IV: 100%. |
| Onset of Action | IV: immediate (peak plasma concentration at end of infusion); oral: 1-2 hours. |
| Duration of Action | 12-24 hours; therapeutic levels maintained with 6-8 hour dosing intervals. |
Intravenous: 500 mg every 6 hours or 500 mg every 8 hours. Typical adult dose: 500 mg IV every 6 hours.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR >10 mL/min. For GFR <10 mL/min, administer 500 mg IV every 12 hours. Metronidazole and metabolites are removed by hemodialysis; administer after dialysis session. |
| Liver impairment | Child-Pugh Class A: No dose adjustment. Child-Pugh Class B: Reduce dose by 50% and consider extended interval (e.g., 500 mg IV every 8-12 hours). Child-Pugh Class C: Reduce dose by 75% (e.g., 250 mg IV every 12 hours or 500 mg IV every 24 hours). |
| Pediatric use | Neonates: 15 mg/kg IV loading dose, then 7.5 mg/kg IV every 12-24 hours depending on gestational age. Infants and children: 10 mg/kg IV every 6-8 hours; maximum 4 g/day. For serious infections, up to 15 mg/kg IV every 6 hours. |
| Geriatric use | No specific dose adjustment; monitor renal function due to age-related decline. For CrCl <10 mL/min, adjust per renal guidelines. Caution with prolonged use due to potential neurotoxicity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Disulfiram-like reaction can occur with alcohol Can cause peripheral neuropathy and seizures with prolonged use.
| FDA category | Human |
| Breastfeeding | Metronidazole is excreted into breast milk with an M/P ratio of approximately 0.9; infant exposure is about 10-20% of maternal dose. Avoid high-dose or prolonged use; after a single 2 g dose, withhold breastfeeding for 12-24 hours; for standard doses, caution advised, though AAP considers compatible. |
| Teratogenic Risk |
■ FDA Black Box Warning
Carcinogenicity in animal studies; reserved for indications where other therapies have been inadequate.
| Common Effects | protozoal infections |
| Serious Effects |
Hypersensitivity to metronidazole or nitroimidazole derivatives, first trimester of pregnancy (unless alternative therapies unavailable), concomitant use with disulfiram (within 2 weeks), concomitant use with alcohol or propylene glycol-containing products.
| Precautions | Carcinogenicity (animal data), seizures and peripheral neuropathy (especially with high doses or prolonged use), disulfiram-like reaction with alcohol, methemoglobinemia, QT prolongation, hepatic impairment (dose adjustment recommended), pregnancy (avoid in first trimester unless essential), lactation (use caution). |
Loading safety data…
| Metronidazole crosses the placenta. First trimester: studies show no consistent increased risk of major malformations, but some reports suggest possible association with cleft lip/palate; avoid unless essential. Second and third trimesters: generally considered safe for short-term use; no evidence of significant fetal harm. |
| Fetal Monitoring | Monitor for signs of neurotoxicity (seizures, peripheral neuropathy) in mother; fetal monitoring not routinely required, but consider ultrasound if used in high doses or prolonged courses. |
| Fertility Effects | No known adverse effects on fertility; animal studies show no impairment. |