rifabutin
Brand: Mycobutin
Prototype: rifampin
Drug Class: rifamycin antibiotic
Drug Family: antibiotic
Subclass: anti-mycobacterial rifamycin
Organ Systems: infectious-disease
Mechanism of Action
Inhibits bacterial DNA-dependent RNA polymerase by binding the beta subunit, blocking transcription; less potent CYP3A4 inducer than rifampin, making it preferred when drug interactions must be minimized (e.g., HIV patients on antiretrovirals).
bacterial DNA-dependent RNA polymerase (beta subunit)
Indications
- Mycobacterium avium complex (MAC) prophylaxis in HIV (CD4 <50)
- MAC treatment (in combination)
- tuberculosis (rifampin-intolerant or drug interactions)
Contraindications
- rifamycin hypersensitivity
- active uveitis
Adverse Effects
Common
- orange-brown discoloration of urine/secretions
- GI upset
- neutropenia
- uveitis (anterior)
Serious
- uveitis (dose-related, can cause blindness if untreated)
- neutropenia/thrombocytopenia
- hepatotoxicity
- drug interactions via moderate CYP3A4 induction
Pharmacokinetics (ADME)
| Absorption | 53% oral bioavailability; food reduces rate but not extent |
| Distribution | large Vd; concentrated in tissues; distributes into macrophages |
| Metabolism | hepatic; moderate CYP3A4 inducer (less than rifampin); active metabolite 25-O-desacetylrifabutin |
| Excretion | biliary (primary) and renal (5%) |
| Half-life | 45 hours |
| Onset | 2–4 hours |
| Peak | 2–4 hours |
| Duration | 24 hours (once-daily) |
| Protein Binding | 85% |
| Vd | very large (8–9 L/kg) |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| HIV protease inhibitors (PI) | PIs increase rifabutin levels via CYP3A4 inhibition; dose reduce rifabutin to 150 mg daily or 300 mg 3x/week | major |
| fluconazole | increases rifabutin levels; risk of uveitis and neutropenia at standard doses | major |
| clarithromycin | CYP3A4 inhibition increases rifabutin; may precipitate uveitis | major |
Nursing Considerations
- Warn patients that urine, sweat, tears, and other secretions may turn orange-brown; this is expected and harmless but can permanently stain soft contact lenses.
- Monitor for uveitis symptoms (eye pain, redness, photophobia, blurred vision) — a dose-related adverse effect unique to rifabutin; ophthalmologic evaluation required if symptoms develop.
- CBC monitoring recommended periodically; rifabutin can cause neutropenia, particularly when combined with macrolides or antifungals that raise rifabutin levels.
- Verify antiretroviral regimen before prescribing; extensive drug interactions with HIV antiretrovirals require dosage adjustments of rifabutin.
Clinical Pearls
- Rifabutin is preferred over rifampin for MAC prophylaxis and TB treatment in HIV-infected patients on protease inhibitors because rifabutin is a weaker CYP3A4 inducer, causing less reduction in antiretroviral drug levels.
- Paradoxically, when HIV protease inhibitors (strong CYP3A4 inhibitors) are co-prescribed with rifabutin, the rifabutin dose must be reduced (not increased) to avoid toxicity from elevated rifabutin levels.
Safety Profile
Pregnancy generally-safe
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Required
TDM Not required
Concordance Terms
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