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

J Clin Pharmacol. 2012 Oct;52(10):1574-83. doi: 10.1177/0091270011419855. Epub 2011 Oct 30.

Abstract

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.

Publication types

  • Clinical Trial, Phase I
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / blood
  • Contraceptives, Oral, Combined / pharmacokinetics*
  • Cross-Over Studies
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Interactions
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / blood
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Follicle Stimulating Hormone / blood
  • Hepacivirus
  • Humans
  • Luteinizing Hormone / blood
  • Middle Aged
  • Norethindrone / administration & dosage
  • Norethindrone / blood
  • Norethindrone / pharmacokinetics*
  • Oligopeptides / administration & dosage
  • Oligopeptides / blood
  • Oligopeptides / pharmacokinetics*
  • Progesterone / blood
  • Protease Inhibitors / administration & dosage
  • Protease Inhibitors / blood
  • Protease Inhibitors / pharmacokinetics*
  • Young Adult

Substances

  • Contraceptives, Oral, Combined
  • Cytochrome P-450 CYP3A Inhibitors
  • Oligopeptides
  • Protease Inhibitors
  • Ethinyl Estradiol
  • Progesterone
  • telaprevir
  • Luteinizing Hormone
  • Follicle Stimulating Hormone
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Norethindrone