bi-201335 and efavirenz

Faldaprevir is a potent, once-daily hepatitis C virus (HCV) NS3/4A protease inhibitor. Studies were performed to investigate potential drug interactions between faldaprevir and the commonly used antiretrovirals darunavir/ritonavir, efavirenz, and tenofovir to guide the coadministration of faldaprevir with these agents in human immunodeficiency virus/HCV-coinfected patients.. In 3 open-label, phase 1 pharmacokinetic (PK) studies, healthy adult volunteers received (1) darunavir/ritonavir (800 mg/100 mg once daily) with and without faldaprevir (240 mg once daily); (2) faldaprevir (240 mg twice daily) with and without efavirenz (600 mg once daily); or (3) faldaprevir (240 mg twice daily) or tenofovir (300 mg once daily) alone and in combination. To assess potential drug interactions, geometric mean ratios and 90% confidence intervals for PK parameters were calculated. Safety was evaluated.. Efavirenz decreased faldaprevir area under the concentration-time curve (AUC) by 35%, Cmax by 28%, and Cmin by 46%, consistent with induction of CYP3A by efavirenz. Tenofovir decreased faldaprevir AUC by 22%, which was not considered to be clinically relevant. Faldaprevir had no clinically relevant effects on darunavir or tenofovir PK (15% and 22% AUC increase, respectively). Adverse events were consistent with the known safety profiles of faldaprevir and the antiretrovirals being examined.. No clinically significant interactions were observed between faldaprevir and darunavir/ritonavir or tenofovir. A potentially clinically relevant decrease in faldaprevir exposure was observed when coadministered with efavirenz; this decrease can be managed using the higher of the 2 faldaprevir doses tested in phase 3 trials (240 mg once daily as opposed to 120 mg once daily).

Topics: Adenine; Adult; Alkynes; Aminoisobutyric Acids; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Benzoxazines; Coinfection; Cyclopropanes; Darunavir; Drug Interactions; Female; Healthy Volunteers; Hepacivirus; Hepatitis C; HIV Infections; HIV-1; Humans; Leucine; Male; Middle Aged; Oligopeptides; Organophosphonates; Proline; Protease Inhibitors; Quinolines; Ritonavir; Sulfonamides; Tenofovir; Thiazoles; Young Adult