metronidazole

Nitroimidazole antibiotic· Brands: Flagyl, Metrogel, Metrocream, Rozex, Anabact, MetrotopIVPOTOP

Mechanism of action

Metronidazole is a prodrug that enters susceptible cells and is reduced by anaerobic organisms to reactive cytotoxic intermediates. These intermediates disrupt DNA structure and function, leading to cell death. The drug is selectively toxic to anaerobes and certain protozoa because they have the necessary reducing environment.

Pharmacokinetics

Metronidazole is well absorbed after oral administration and has good tissue penetration, including the central nervous system. It is metabolised in the liver, mainly by oxidation, and both the parent drug and metabolites are excreted in urine. The elimination half-life is about 8 hours, but may be prolonged in hepatic impairment.

Indications & dosing

Anaerobic bacterial infection

For mild to moderate anaerobic infections; alternative IV therapy for severe cases.

adult · PO: 400 mg three times daily · For mild to moderate anaerobic infections; alternative IV therapy for severe cases.

Anaerobic bacterial infection

For severe anaerobic infections when oral route not feasible.

adult · IV: 500 mg every 8 hours · For severe anaerobic infections when oral route not feasible.

Trichomoniasis

Alternative: 400 mg twice daily for 7 days.

adult · PO: 2000 mg single dose · Alternative: 400 mg twice daily for 7 days.

Giardiasis

Alternative: 400 mg three times daily for 5 days.

adult · PO: 2000 mg daily for 3 days · Alternative: 400 mg three times daily for 5 days.

Amoebiasis (invasive)

For intestinal and extraintestinal amoebiasis; usually followed by a luminal amoebicide.

adult · PO: 800 mg three times daily · For intestinal and extraintestinal amoebiasis; usually followed by a luminal amoebicide.

Clostridioides difficile infection

No longer first-line; reserve for when fidaxomicin or vancomycin is unavailable or unsuitable; refer to local guidance.

adult · PO: 400 mg three times daily · First-line for mild infection; refer to local guidance.

Bacterial vaginosis

Alternative: 2 g single dose.

adult · PO: 400 mg twice daily · Alternative: 2 g single dose.

Contraindications & precautions

Hypersensitivity to metronidazole or other nitroimidazoles · Includes patients with a history of hypersensitivity to related drugs.
Concurrent use with disulfiram · Risk of acute psychosis or confusional states; separate by at least 2 weeks.
Alcohol intake during and for 48 hours after therapy · Risk of disulfiram-like reaction with abdominal cramps, nausea, vomiting, and headache.
First trimester of pregnancy · Use only if essential; seek specialist advice.
Avoid alcohol during and for at least 48 hours after completing therapy to prevent disulfiram-like reaction.
Use with caution in patients with severe hepatic impairment; consider dose reduction.
Monitor for neurological symptoms such as paraesthesia, ataxia, or seizures; discontinue therapy if these occur.
Caution in patients with a history of blood dyscrasias; full blood count should be monitored during prolonged therapy.
Metronidazole may enhance the effect of warfarin; monitor INR closely.
In renal impairment, reduce dose if severe (creatinine clearance <10 mL/min).

Adverse effects

Metallic taste
Nausea and vomiting
Headache
Peripheral neuropathyserious
Seizuresserious
Encephalopathyserious
Optic neuritisserious
Agranulocytosis or neutropeniaserious

Interactions

warfarinmajorAvoid concomitant use if possible. If co-administration is necessary, monitor the INR frequently (e.g., every 2 to 3 days) for the first week of metronidazole therapy and for several days after discontinuation, and adjust the warfarin dose accordingly to maintain the target INR. Consider using an alternative antibiotic with no known interaction (e.g., a penicillin or macrolide, depending on the infection). Educate the patient about signs of bleeding and the need for prompt medical review.

Renal & hepatic adjustment

eGFR 0+: No dose adjustment required in renal impairment.
Hepatic impairment (mild): No dose adjustment required.
Hepatic impairment (moderate): No adjustment required; monitor for adverse effects.
Hepatic impairment (severe): Avoid in severe hepatic impairment; consider an alternative agent. (avoid)

Monitoring, pregnancy & toxicity

Neurotoxicity (seizures, peripheral neuropathy) · During prolonged therapy
International normalised ratio (INR) · If co-administered with warfarin
Liver function tests · In patients with hepatic impairment
White blood cell count · During prolonged therapy
Pregnancy: Metronidazole may be used when clinically indicated, but alternatives should be considered in the first trimester. Accumulated evidence suggests safety, but caution is advised. Discuss with the patient.
Toxicity: Peripheral neuropathy · Discontinue therapy and provide supportive care. Symptoms may be reversible upon discontinuation.
Toxicity: Seizures · Discontinue drug and treat with an appropriate benzodiazepine.
Toxicity: Disulfiram-like reaction with alcohol · Avoid alcohol and alcohol-containing products during and for at least 3 days after therapy; treat symptomatically.
Toxicity: Nausea and metallic taste · Usually transient and dose-related; advise the patient to take with food to reduce GI upset.

Clinical notes

Metronidazole is used for anaerobic and protozoal infections, including bacterial vaginosis, trichomoniasis, amoebiasis, and infections caused by Bacteroides species. It is also used for Helicobacter pylori eradication in combination regimens. Common adverse effects include nausea, metallic taste, and peripheral neuropathy with prolonged use. Alcohol should be avoided during therapy and for 48 hours after completion due to a disulfiram-like reaction. Dose adjustment may be needed in severe hepatic impairment.

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BNF; local formulary