Metronidazole for Protozoal Disease

Metronidazole is a nitroimidazole with activity against Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis, and against anaerobic bacteria. It is the first-line drug for invasive amoebiasis and amoebic liver abscess, and an alternative for giardiasis and trichomoniasis. It cures tissue disease but not luminal cysts, so a luminal agent follows. It causes a metallic taste and a disulfiram-type reaction with alcohol.

Class. Antiprotozoal; 5-nitroimidazole.

Mechanism. The nitro group is reduced inside anaerobic organisms to reactive intermediates that damage DNA, killing the organism. It acts on trophozoites in tissue.

Pharmacokinetics. Oral bioavailability over 90%. Half life 8 hours. Widely distributed, including cerebrospinal fluid, pus and liver. Metabolised in the liver; excreted in urine.

Invasive amoebiasis (dysentery or liver abscess), adults. 750 mg orally three times daily for 7 to 10 days (500 mg intravenously every 8 hours if unable to take oral). Follow with a luminal agent.

Children. 30 to 50 mg/kg daily in three doses for 7 to 10 days (maximum 2.25 g daily).

Luminal agents after metronidazole. Paromomycin 25 to 35 mg/kg daily in three doses for 7 days, or diloxanide furoate 500 mg three times daily for 10 days.

Giardiasis. 250 mg three times daily for 5 to 7 days (children 15 mg/kg daily in three doses for 5 days).

Trichomoniasis. 500 mg twice daily for 7 days in women; 2 g as a single dose in men; treat partners.

Dose adjustment for liver function. In Child-Pugh C impairment, reduce the dose by 50%.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 4 g daily.

Main alternative. Tinidazole.

Contraindications. Hypersensitivity to nitroimidazoles; disulfiram use within 2 weeks; first trimester of pregnancy for high doses (relative).

Serious adverse effects. Peripheral neuropathy and encephalopathy with long courses, seizures, severe skin reactions, hepatotoxicity (rare), QT prolongation and neutropenia.

Common adverse effects. Metallic taste, nausea, vomiting, headache, dark urine and furred tongue.

Interactions. - Alcohol: flushing, vomiting and tachycardia (disulfiram-type reaction); avoid during treatment and for 48 hours after. - Warfarin: INR rises. - Lithium, busulfan and ciclosporin levels rise. - Phenytoin and phenobarbital lower metronidazole; cimetidine raises it.

Common prescribing errors. Treating amoebic liver abscess without a luminal agent afterwards, long courses without neuropathy checks, and drinking alcohol during treatment.

Special groups. - Pregnancy: acceptable when needed, particularly after the first trimester. - Breastfeeding: compatible with short courses; infant monitoring. - Children: weight-based dosing. - Older adults: usual dose; watch for neuropathy. - Kidney impairment: no adjustment; give after haemodialysis. - Liver impairment: reduce by 50% in Child-Pugh C.

Regional points. Amoebiasis and giardiasis are common in children in East Africa, often treated empirically without stool tests, so luminal clearance after invasive amoebiasis is often missed.

Formulations. Tablets 200 mg, 250 mg, 400 mg and 500 mg; suspension 200 mg/5 mL; intravenous infusion 500 mg/100 mL.

Administration. Oral after food to reduce nausea. Intravenous: infuse over 30 to 60 minutes.

Baseline. Diagnosis by stool microscopy or antigen where available, liver tests in liver disease, pregnancy status, alcohol history.

Monitoring. Clinical response at 48 to 72 hours; neuropathy and mental state during long courses; full blood count if repeated courses.

Stopping thresholds. Stop for new neuropathy, seizures, encephalopathy or severe skin reaction.

Referral and escalation. Specialist or surgical review for large or ruptured liver abscess, fulminant colitis, and treatment failure.