Drug Interactions between amoxicillin / omeprazole / rifabutin and darunavir

ADJUST DOSE: Coadministration of rifabutin and darunavir/ritonavir is expected to increase the plasma concentrations of rifabutin and its 25-O-desacetylrifabutin metabolite and may also increase the plasma concentrations of darunavir and ritonavir. The proposed mechanism involves ritonavir inhibition of rifabutin metabolism via CYP450 3A4. In 11 study subjects, administration of lower-dose rifabutin (150 mg every other day for 12 days) and darunavir/ritonavir (600 mg/100 mg twice daily for 12 days) resulted in non-significant changes in the peak plasma concentration (Cmax), systemic exposure (AUC), and trough plasma concentration (Cmin) of rifabutin, as compared to the standard dose of rifabutin alone (300 mg once daily). In the same study, Cmax, AUC, and Cmin of darunavir were increased by 57%, 42% and 75% respectively. Uveitis secondary to rifabutin toxicity has been reported in some cases.

MANAGEMENT: To minimize the risk of rifabutin toxicity including leukopenia, uveitis, arthralgias and skin discoloration, darunavir labeling recommends that rifabutin dosage be reduced to 150 mg every other day in patients treated with darunavir/ritonavir or darunavir/cobicistat. A complete blood count should be performed at least weekly and as clinically indicated to monitor for development of neutropenia. Local guidelines should be consulted for appropriate recommendations.