Drug Interactions between atazanavir and rifabutin

ADJUST DOSE: Coadministration with atazanavir may significantly increase the plasma concentrations of rifabutin and its active 25-O-desacetyl metabolite. The mechanism is atazanavir inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of rifabutin. In 3 study subjects, atazanavir (600 mg once a day for 10 days) increased the mean steady-state peak plasma concentration (Cmax), area under the concentration-time curve (AUC) and trough plasma concentration (Cmin) of rifabutin (150 mg once a day for 10 days) by 18%, 110% and 243%, respectively, compared to administration of rifabutin alone at 300 mg once a day. The Cmax, AUC and Cmin of the 25-O-desacetyl metabolite were 8, 22, and 75 times the values observed with rifabutin alone at 300 mg once a day.

MANAGEMENT: Use of the fixed combination atazanavir-cobicistat with rifabutin is not recommended and some authorities consider the use to be contraindicated. However, if concomitant use is needed, some authorities recommend a reduction in the rifabutin dosage of up to 75% (e.g., 150 mg every other day or three times per week). A further dosage reduction of rifabutin to 150 mg twice weekly may be necessary for patients in whom the 150 mg three times per week dose is not tolerated. Patients should be monitored for rifabutin toxicity such as leucopenia, uveitis, arthralgias and skin discoloration. Current guidelines should be consulted for the appropriate treatment of tuberculosis in HIV infected patients.

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