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. |
| Molecular Weight | 171.15 Da (as hydrochloride salt; base: 171.15 Da) |
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 | Metronidazole hydrochloride crosses the placenta. Use in first trimester only if clearly needed; available data do not suggest an increased risk of major birth defects. |
| 2nd trimester | Use in second trimester if clearly indicated; considered compatible with use during pregnancy. |
| 3rd trimester | Use in third trimester if clearly indicated; may be used for symptomatic trichomoniasis or bacterial vaginosis. |
Clinical note
Disulfiram-like reaction can occur with alcohol Can cause peripheral neuropathy and seizures with prolonged use.
| FDA category | Human |
| Placental transfer | Metronidazole crosses the placenta readily, achieving fetal serum concentrations similar to maternal levels. |
| Breastfeeding |
■ 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 any component of the formulationPregnancy (first trimester) for the treatment of trichomoniasis (relative contraindication; use only if clearly needed)Concurrent use with disulfiram (psychotic reactions may occur)Concurrent use with alcohol or propylene glycol-containing products (disulfiram-like reaction)
| 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). |
| Food/Dietary |
Loading safety data…
| Metronidazole is excreted into breast milk in concentrations similar to maternal plasma. The American Academy of Pediatrics considers it compatible with breastfeeding. However, because of concerns from animal carcinogenicity data, some clinicians recommend avoiding high doses or discontinuing breastfeeding during high-dose therapy; a single 2g dose may be given with interruption of breastfeeding for 12-24 hours. |
| Lactation Rating | L3 (Moderately Safe) / Compatible |
| Teratogenic Risk | 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. |
| Alcohol must be strictly avoided during therapy and for at least 48 hours after completion to prevent a disulfiram-like reaction (nausea, vomiting, flushing, headache). No other significant food interactions; however, taking with meals can reduce gastrointestinal upset. |
| Clinical Pearls | Metronidazole hydrochloride is metabolized hepatically and excreted renally; dosing adjustment needed for severe hepatic impairment (Child-Pugh C). Avoid alcohol during therapy and for 48 hours after completion due to disulfiram-like reaction. Monitor for peripheral neuropathy with prolonged use; discontinue if signs appear. IV formulation contains sodium; caution in heart failure or hypertension. Drug interactions: warfarin (enhanced anticoagulation), lithium (increased toxicity), phenytoin (increased phenytoin levels), and cimetidine (decreased clearance). |
| Patient Advice | Finish the entire course of medication even if you feel better. · Avoid alcohol and any alcohol-containing products (e.g., mouthwash, cough syrup) during treatment and for 48 hours after the last dose; serious nausea, vomiting, and headache may occur. · Take with food to reduce stomach upset. · Metronidazole may cause a metallic taste; this is temporary. · Contact your healthcare provider if you experience numbness or tingling in your hands or feet. · This medication can cause dizziness; avoid driving or operating machinery if affected. · Inform your doctor if you are pregnant, planning to become pregnant, or breastfeeding. · Report any signs of new infection, such as fever or chills. |