Furazolidone

Furazolidone is a nitrofuran used orally for intestinal infection, including giardiasis, cholera and bacterial diarrhoea, and in some regions as part of rescue Helicobacter pylori therapy. It has been withdrawn in many countries because of carcinogenicity concerns in animals and its monoamine oxidase inhibition.

Classification. Nitrofuran.

Mechanism. Reduced to reactive intermediates that damage bacterial and protozoal DNA and enzymes; bactericidal. It also inhibits monoamine oxidase.

Spectrum. Giardia lamblia, Vibrio cholerae, Shigella, Salmonella, Escherichia coli, Campylobacter, Helicobacter pylori and Trichomonas vaginalis.

Pharmacokinetics. Poorly absorbed from the gut, with high intraluminal levels. Minimal systemic exposure. Metabolites colour the urine brown.

Availability in East Africa is very limited and use is region-specific. Maximum 400 mg daily, for 10 days at most.

Adults, oral. - Giardiasis: 100 mg every 6 hours for 7 to 10 days. - Cholera and bacterial diarrhoea: 100 mg every 6 hours for 3 to 5 days. - Helicobacter pylori rescue (regional regimens): 100 mg every 12 hours for 10 to 14 days in combination with a proton pump inhibitor, bismuth and an antibiotic partner.

Children over 1 month. 5 to 8.8 mg/kg/day in 4 divided doses for 7 days (maximum 400 mg daily). Not advised under 1 month (haemolysis).

Alternatives. Metronidazole, tinidazole, secnidazole (giardiasis); azithromycin, ciprofloxacin (cholera and diarrhoea); bismuth quadruple therapy (Helicobacter pylori).

Contraindications. Infants under 1 month; glucose 6-phosphate dehydrogenase deficiency; hypersensitivity; concurrent monoamine oxidase inhibitors, sympathomimetics and tyramine-rich food.

Adverse effects. Nausea, vomiting, abdominal pain, headache, brown urine. Serious: haemolysis (G6PD deficiency and neonates), hypersensitivity reactions, disulfiram-like reaction with alcohol, hypertensive crisis with tyramine or sympathomimetics, polyneuropathy with prolonged use, hypoglycaemia.

Interactions. Alcohol (disulfiram-like; avoid during and for 4 days after); monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors, sympathomimetics, tyramine-rich food, pethidine and levodopa (hypertensive crisis or serotonin syndrome); antidiabetic drugs.

Common prescribing errors. Alcohol or tyramine-rich food during treatment, use in infants, use with antidepressants, and prolonged courses.

Special groups. - Pregnancy: avoid (haemolysis risk at term and animal carcinogenicity concerns). Breastfeeding: avoid. - Older adults: usual dose; monitor blood pressure. - Kidney impairment: use with caution; limited systemic data. - Liver impairment: use with caution. - Region: limited and variable availability in East Africa; metronidazole or tinidazole is usually used instead.

Administration. Oral with food; avoid alcohol and tyramine-rich foods during treatment and for 4 days after.

Baseline and monitoring. - Baseline: medication review, G6PD status where available, pregnancy status, blood pressure. - During treatment: symptom review at 3 to 5 days; blood pressure and haemolysis signs in prolonged use.

Stop rules. Stop for haemolysis, hypertensive headache, severe rash, jaundice, paraesthesia or confusion.

Referral and escalation. Refer for haemolysis, treatment failure and persistent diarrhoea.