The pharmacokinetic interaction between an oral contraceptive containing ethinyl estradiol and norethindrone and the HCV protease inhibitor telaprevir.

Background: Telaprevir is a hepatitis C virus protease inhibitor that is both a substrate and an inhibitor of CYP3A.

Study Design: The effect of steady-state telaprevir (administered 750 mg every 8 hours) on the steady-state pharmacokinetics of ethinyl estradiol (EE) and norethindrone (NE) was evaluated in 24 healthy women receiving oral contraceptives (OC) containing 0.5 mg NE and 0.035 mg EE for at least 3 months at the time of screening. This was a phase 1, open-label, single-center, nonrandomized study that included a cycle 1 (OC only for 21 days, followed by no OC for 7 days), cycle 2 (OC plus telaprevir for 21 days, followed by telaprevir alone for 7 days), and a follow-up period.

Results: When administration with or without telaprevir was compared, the least-squares mean ratios (90% confidence limits) for EE were 0.74 (0.68; 0.80) for C(max), 0.67 (0.63; 0.71) for C(min), and 0.72 (0.69; 0.75) for AUC; neither NE nor telaprevir exposure was affected.

Conclusions: The efficacy of the OC may be compromised by the 26% to 33% reduction in EE exposure. Therefore, alternative methods of nonhormonal contraception should be used when hormonal contraceptives are coadministered with telaprevir and for up to 2 weeks following cessation of telaprevir.