Nitazoxanide

Nitazoxanide is an oral thiazolide antiparasitic with activity against Cryptosporidium, Giardia and some helminths. It shortens diarrhoea in children and immunocompetent adults with cryptosporidiosis, but has modest effect in advanced HIV, where immune recovery with antiretroviral therapy matters more. It is well tolerated and discolours urine and sclerae yellow.

Class. Antiparasitic; thiazolide.

Mechanism. The active metabolite tizoxanide inhibits pyruvate-ferredoxin oxidoreductase, an enzyme needed for anaerobic energy metabolism in protozoa and anaerobic bacteria.

Pharmacokinetics. Rapidly hydrolysed to tizoxanide, which is highly protein bound. Absorption increased by food. Half life about 1.5 hours. Excreted in urine and bile.

Cryptosporidiosis and giardiasis. 500 mg orally twice daily with food for 3 days (adults and children 12 years and over). - Children 1 to 3 years: 100 mg twice daily for 3 days. - Children 4 to 11 years: 200 mg twice daily for 3 days.

Cryptosporidiosis in advanced HIV. 500 mg twice daily for 14 days or until diarrhoea resolves, with antiretroviral therapy started or optimised at once.

Loading dose, maintenance dose and titration. Not applicable. Maximum: 1000 mg daily.

Main alternatives. Supportive care with rehydration; antiretroviral therapy in HIV; metronidazole or tinidazole for giardiasis.

Contraindications. Hypersensitivity.

Serious adverse effects. Hypersensitivity reactions (rare).

Common adverse effects. Abdominal pain, nausea, diarrhoea, headache and yellow discolouration of urine and sclerae.

Interactions. Warfarin and other highly protein-bound drugs may rise; no CYP interactions of importance.

Common prescribing errors. Expecting cure in advanced HIV without starting antiretroviral therapy, and giving fasting.

Special groups. - Pregnancy: limited data; use only when needed. - Breastfeeding: limited data. - Children: from 1 year; suspension by age. - Older adults: usual dose. - Kidney impairment: no adjustment. - Liver impairment: use with care.

Regional points. Cryptosporidiosis is a leading cause of persistent diarrhoea in children with HIV or malnutrition in East Africa; availability is limited, and rehydration, nutrition and antiretroviral therapy are the main treatment.

Formulations. Tablets 500 mg; powder for oral suspension 100 mg/5 mL.

Administration. With food, twice daily.

Baseline. Hydration status, HIV status and CD4 count, stool microscopy where available.

Monitoring. Stool frequency, weight and hydration daily during admission; CD4 and viral load in HIV.

Stopping thresholds. Stop for hypersensitivity.

Referral and escalation. Admission for severe dehydration, persistent diarrhoea beyond 14 days, or malnutrition.