Rifabutin × Voriconazole

The interaction runs both ways. Voriconazole inhibits CYP3A4, the liver enzyme that breaks down rifabutin. With voriconazole 400 mg twice daily, the rifabutin area under the curve (AUC) rose by 331% and peak concentration by 195%. Rifabutin in turn speeds up voriconazole metabolism: at the usual 200 mg twice daily, voriconazole AUC fell by 78% and peak concentration by 69%. At 350 mg twice daily, voriconazole peak concentration was close to the usual level (4% lower), but AUC stayed 32% lower than with 200 mg without rifabutin. At 400 mg twice daily, voriconazole peak concentration and AUC almost doubled.

Excess rifabutin can show as uveitis: eye pain and redness, photophobia, blurred vision. Neutrophil and, less often, platelet counts fall, which can lead to fever, infections or bruising. Too little voriconazole shows as a fungal infection that does not respond to treatment: fever persists and lesions in the lungs or other organs do not regress.

The combination is contraindicated in the US labels of both voriconazole and rifabutin (US Food and Drug Administration, FDA). In Europe it is not contraindicated, but avoid it unless the benefit outweighs the risk (voriconazole SmPC, European Medicines Agency, EMA; rifabutin ficha técnica, Spanish Agency of Medicines, AEMPS). If there is no alternative to rifabutin, raise the voriconazole maintenance dose: orally from 200 to 350 mg twice daily (from 100 to 200 mg twice daily in patients under 40 kg), or intravenously to 5 mg/kg twice daily (voriconazole SmPC, EMA). Throughout co-administration, closely monitor the full blood count and adverse effects of rifabutin, especially uveitis (voriconazole SmPC, EMA). If uveitis is suspected, refer the patient to an ophthalmologist and stop rifabutin if needed (rifabutin ficha técnica, AEMPS).