Tinidazole

Tinidazole is a second-generation nitroimidazole with a longer half-life than metronidazole, allowing single-dose or short-course treatment of giardiasis, amoebiasis, trichomoniasis and bacterial vaginosis. It has similar anaerobic activity and the same alcohol interaction.

Classification. Nitroimidazole.

Mechanism. The nitro group is reduced in anaerobic organisms, producing free radicals that break DNA; bactericidal and antiprotozoal.

Spectrum. Bacteroides, Fusobacterium, Clostridium, Peptostreptococcus, Gardnerella, Helicobacter pylori (resistance common), Trichomonas vaginalis, Entamoeba histolytica and Giardia lamblia.

Pharmacokinetics. Oral bioavailability over 90%. Half-life 12 to 14 hours. Protein binding about 12%. Good tissue and CSF penetration. Hepatic metabolism with mostly renal excretion.

Maximum 2 g daily.

Adults, oral, take with food. - Giardiasis: 2 g as a single dose. - Intestinal amoebiasis: 2 g once daily for 3 days. - Amoebic liver abscess: 2 g once daily for 3 to 5 days (6 days in some severe disease), followed by a luminal agent. - Trichomoniasis: 2 g as a single dose, with simultaneous partner treatment. - Bacterial vaginosis: 2 g once daily for 2 days, or 1 g once daily for 5 days. - Anaerobic infection: 2 g on day 1 then 1 g once daily for 5 to 6 days (up to 10 days). - Surgical prophylaxis: 2 g as a single dose about 12 hours before surgery.

Children over 3 years. Giardiasis 50 mg/kg as a single dose (maximum 2 g). Amoebiasis 50 mg/kg once daily for 3 days (liver abscess 3 to 5 days; maximum 2 g a day).

Alternatives. Metronidazole, secnidazole, ornidazole, paromomycin (luminal amoebiasis).

Contraindications. Nitroimidazole hypersensitivity; first trimester pregnancy; blood dyscrasias; active neurological disease (relative); alcohol during treatment and for 72 hours after.

Adverse effects. Metallic taste, nausea, vomiting, anorexia, dizziness, headache, dark urine. Serious: peripheral neuropathy, seizures, leucopenia, severe skin reactions, hepatotoxicity, QT prolongation (rare).

Interactions. Alcohol (disulfiram-like reaction; avoid for 72 hours after); warfarin (INR rise); lithium; phenytoin; fluorouracil; busulfan; disulfiram; QT-prolonging drugs; phenobarbital and rifampicin (lower levels).

Common prescribing errors. Alcohol during or soon after treatment, no luminal agent after invasive amoebiasis, and using it in the first trimester.

Special groups. - Pregnancy: avoid in the first trimester; use after that only if needed. Breastfeeding: avoid during treatment and for 3 days after the last dose (discard milk). - Older adults: usual dose. - Kidney impairment: no adjustment; haemodialysis removes the drug, so give an extra dose or give after the session. - Liver impairment: use with caution; reduce the dose in severe disease. - Region: available in East Africa where single-dose compliance is useful in giardiasis and amoebiasis.

Administration. Take with food. Tablets can be crushed in a sweet food or syrup for children.

Baseline and monitoring. - Baseline: medication review, alcohol history, neurological history, pregnancy status. - During treatment: neurological symptoms and blood count if the course is prolonged or repeated.

Stop rules. Stop for new paraesthesia, ataxia, seizures, severe rash or jaundice.

Referral and escalation. Refer for amoebic abscess not responding at 72 hours, neurotoxicity and treatment failure.