Rifabutin

Rifabutin is a rifamycin with weaker enzyme induction than rifampicin, used for tuberculosis when rifampicin interacts with essential drugs (especially protease-inhibitor-based antiretroviral therapy), for Mycobacterium avium complex infection and Helicobacter pylori rescue therapy.

Classification. Rifamycin.

Mechanism. Binds the beta subunit of bacterial RNA polymerase and blocks transcription; bactericidal.

Spectrum. Mycobacterium tuberculosis (including some rifampicin-resistant strains), Mycobacterium avium complex, Mycobacterium kansasii, Staphylococcus aureus, Helicobacter pylori. Cross-resistance with rifampicin is common.

Pharmacokinetics. Oral bioavailability about 20%. Half-life 32 to 67 hours. Extensive tissue distribution, with tissue levels many times higher than plasma. Hepatic metabolism (CYP3A4 substrate) with renal and biliary excretion. Colours body fluids orange-brown.

Maximum 600 mg daily.

Adults, oral.

• Tuberculosis: 300 mg once daily (5 mg/kg), for 6 months, in place of rifampicin when interactions require it.
• Tuberculosis with a ritonavir- or cobicistat-boosted protease inhibitor: 150 mg once daily (or 150 mg every 48 hours, or 300 mg three times weekly), with the dose set by the antiretroviral regimen.
• Tuberculosis with efavirenz: 450 mg once daily.
• Mycobacterium avium complex treatment: 300 mg once daily with a macrolide and ethambutol (150 mg daily with clarithromycin, to limit uveitis and levels).
• Mycobacterium avium complex prophylaxis (advanced HIV, where antiretroviral therapy is delayed): 300 mg once daily.
• Helicobacter pylori rescue: rifabutin 50 mg (or 150 mg) every 8 hours with amoxicillin 1 g every 8 hours and a proton pump inhibitor, for 14 days (specialist).

Children. 5 to 10 mg/kg once daily (maximum 300 mg); limited data under 12 years.

Alternatives. Rifampicin, rifapentine.

Contraindications. Rifamycin hypersensitivity; active hepatitis or jaundice; severe neutropenia or thrombocytopenia.

Adverse effects. Orange-brown body fluids, rash, nausea, vomiting, abdominal pain, headache. Serious: uveitis (often with clarithromycin, fluconazole or higher doses), neutropenia, thrombocytopenia, arthralgia and myalgia, hepatotoxicity, flu-like syndrome, Clostridioides difficile infection.

Interactions. Substrate of CYP3A4: levels rise with clarithromycin, azole antifungals and protease inhibitors (reduce rifabutin dose) and fall with efavirenz (increase the dose). Weak inducer: hormonal contraception (use a non-hormonal or depot method), warfarin and direct oral anticoagulants, antiepileptics, dolutegravir (usual dose, no change), methadone, sulphonylureas, ciclosporin.

Common prescribing errors. Wrong rifabutin dose with protease inhibitors or efavirenz, missing uveitis symptoms, and using it with contraceptive pills while relying on them.

Special groups. - Pregnancy: use only when needed (limited data); give vitamin K near term. Breastfeeding: acceptable with infant monitoring. - Older adults: monitor counts and liver tests. - Kidney impairment: creatinine clearance under 30 mL/min reduce the dose by 50%. - Liver impairment: avoid in significant disease. - Region: available in East Africa mainly through tuberculosis and HIV programmes, in limited quantity.

Administration. Oral with or without food (food helps tolerance).

Baseline and monitoring. - Baseline: full blood count, liver tests, visual symptoms, medication review. - During treatment: full blood count and liver tests monthly; ask about eye pain, redness and blurred vision.

Stop rules. Stop for uveitis (stop and refer), neutropenia under 1000 cells/microlitre with fever, jaundice, severe rash or hypersensitivity.

Referral and escalation. Refer for uveitis (ophthalmology), antiretroviral therapy dose planning, and drug-resistant tuberculosis.