Based on theoretical considerations rifapentine is expected to decrease darunavir and/or cobicistat plasma concentrations (CYP3A induction). Co-administration of darunavir/cobicistat with rifapentine is not recommended. Consideration should be given to official guidance on the appropriate treatment of tuberculosis in HIV infected patients. [This recommendation is different from ritonavir-boosted darunavir. Consult the Summary of Product Characteristics for darunavir for further details.]

Coadministration is expected to decrease concentrations of darunavir. Co-administration with rifapentine is not recommended.

The pharmacokinetic of darunavir/cobicistat (800/150 mg once daily) were evaluated when coadministered with once weekly rifapentine + isoniazid given for 3 months (3HP). Healthy volunteers received darunavir/cobicistat 800/150 mg once daily alone for 4 days then continued darunavir/cobicistat once daily for days 5-19 with weekly 3HP coadministration on days 5, 12 and 19. Intensive PK assessment were performed on day 4 (darunavir/cobicistat alone), 14 (darunavir/cobicistat 48-72 hours after 3HP) and 19 (darunavir/cobicistat simultaneously with 3HP). Relative to darunavir/cobicistat alone, darunavir AUC0-24h, C0h, Cmax and C24h were significantly decreased with 3HP coadministration with more marked decreases 48-72 hours after rifapentine administration (day 14) in comparison to simultaneous administration (day 19). Darunavir AUC0-24h, C0h and C24 h ratios were 0.29, 0.04 and 0.04, respectively on day 14 relative to darunavir/cobicistat alone. Darunavir AUC0-24h, C0h and C24 h ratios were 0.64, 0.19 and 0.11, respectively on day 19 relative to darunavir/cobicistat alone. CL/F was increased and V/F differed depending on the timing of 3HP administration, suggesting induction and changes in bioavailability, respectively, with 3HP. On day 14, several individual C0h and C24h were below the darunavir EC50. This study shows that darunavir exposure was significantly decreased with 3HP coadministration. Multiple trough concentrations fell below the darunavir EC50 thus coadministration between darunavir/cobicistat should be avoided.