BLACK BOX WARNING
- carcinogenic in rodents — avoid unnecessary prolonged use or high doses
metronidazole
Brand: Flagyl, Metro
⚠ BBW Prototype Drug
Drug Class: antibiotic / antiprotozoal
Drug Family: antibiotic
Subclass: nitroimidazole
Organ Systems: infectious-disease
Mechanism of Action
Prodrug reduced in anaerobic organisms to a cytotoxic nitro radical anion, which damages microbial DNA and causes strand breaks; bactericidal against obligate anaerobes and protozoa; aerobic organisms cannot reduce the drug to its active form.
microbial DNA (reactive intermediate)
Indications
- Clostridioides difficile colitis (vancomycin or fidaxomicin preferred for severe cases)
- bacterial vaginosis
- trichomoniasis (drug of choice)
- intra-abdominal infections (with cephalosporin for aerobic coverage)
- amoebic liver abscess
- H. pylori eradication (component)
- anaerobic wound infections
Contraindications
- first trimester of pregnancy (teratogenicity concerns)
- disulfiram reaction (concurrent disulfiram or within 2 weeks)
Adverse Effects
Common
- metallic taste
- nausea
- headache
- dizziness
Serious
- peripheral neuropathy (dose-dependent; prolonged use)
- CNS neurotoxicity (encephalopathy, cerebellar dysfunction, seizures — mainly high-dose IV)
- disulfiram-like reaction with alcohol
- Clostridioides difficile superinfection (paradoxically)
Pharmacokinetics (ADME)
| Absorption | ~100% oral bioavailability |
| Distribution | Protein binding <20%; Vd ~0.25–0.85 L/kg; excellent CSF penetration |
| Metabolism | Hepatic CYP2C9 and CYP3A4 (minor) to active hydroxy-metabolite |
| Excretion | Renal (~60–80%) and fecal |
| Half-life | 6–12 hours |
| Onset | 1–2 hours |
| Peak | 1–2 hours |
| Duration | 8–12 hours |
| Protein Binding | <20% |
| Vd | 0.25–0.85 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| alcohol | disulfiram-like reaction (flushing, nausea, tachycardia, hypotension) — avoid alcohol during and 48 hours after therapy | major |
| warfarin | CYP2C9 inhibition increases warfarin levels; INR may double | major |
| lithium | may reduce renal lithium clearance; toxicity risk | moderate |
Nursing Considerations
- Counsel patients emphatically about the disulfiram-like reaction with alcohol — avoid all alcohol (including mouthwash, food preparations) during therapy and for 48–72 hours after completion
- For trichomoniasis: treat both partners simultaneously regardless of symptoms; use 2 g single-dose regimen or 500 mg BID x7 days; retest at 3 months
- Monitor for peripheral neuropathy (tingling, numbness in extremities) with prolonged courses — generally reversible but can persist; report immediately
- IV metronidazole for severe C. diff or intra-abdominal anaerobic infections: infuse over 30–60 minutes; IV formulation contains significant propylene glycol (monitor for toxicity with extended infusions)
Clinical Pearls
- Metronidazole is unique among antibiotics in its complete selectivity for obligate anaerobes — aerobic organisms cannot reduce the drug to its toxic intermediate, meaning aerobes are completely unaffected
- The disulfiram-like reaction is not a drug allergy — it is a predictable pharmacodynamic interaction from acetaldehyde accumulation; the interaction is severe enough to warrant strict counseling and documentation
Safety Profile
Pregnancy avoid
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.
Amoebic Liver Abscess Anaerobic Wound Infections Antibiotic / Antiprotozoal Bacterial Vaginosis Clostridioides Difficile Colitis (vancomycin Or Fidaxomicin Preferred For Severe Cases) H. Pylori Eradication (component) Intra-abdominal Infections (with Cephalosporin For Aerobic Coverage) Trichomoniasis (drug Of Choice)