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.


METHODS
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.
Vertex Pharmaceuticals Incorporated, Cambridge, MA 02139-4242, USA. varun_garg@vrtx.com
Varun
V
Garg
Rolf
R
van Heeswijk
Yijun
Y
Yang
Robert
R
Kauffman
Frances
F
Smith
Nathalie
N
Adda
D000328:Adult; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004997:Ethinyl Estradiol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D016174:Hepacivirus; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D009842:Oligopeptides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D011374:Progesterone / Q000097:blood; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D003277:Contraceptives, Oral, Combined; D065692:Cytochrome P-450 CYP3A Inhibitors; D009842:Oligopeptides; D011480:Protease Inhibitors; D004997:Ethinyl Estradiol; D011374:Progesterone; C486464:telaprevir; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009640:Norethindrone