The effect of efavirenz on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy HIV-negative women

Antivir Ther. 2011;16(2):149-56. doi: 10.3851/IMP1725.


Background: Women of childbearing age represent a growing proportion of people living with HIV. Preventing pregnancy is important in HIV-infected women receiving efavirenz as part of their antiretroviral therapy.

Methods: The effects of coadministration of efavirenz (600 mg once daily) on the pharmacokinetics (PK) of the active components (ethinyl estradiol [EE] and 17-deacetyl norgestimate [NGMN]) of Ortho Cyclen(®) (Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ, USA) were investigated in 28 healthy HIV-negative women. The peak plasma concentration (C(max)), area under the concentration-time curve for a dosing interval (AUC([τ])), and lowest plasma concentration (C(min)) for EE and NGMN during cycles of treatment with Ortho Cyclen with and without coadministration of efavirenz were compared. Additionally, a post hoc exploratory analysis was conducted to assess the effect of efavirenz on the PK of an additional progestin, levonorgestrel (LNG).

Results: Exposures to EE were similar during coadministration of efavirenz and Ortho Cyclen to those during administration of Ortho Cyclen alone. Exposures to NGMN were substantially decreased following coadministration of efavirenz and Ortho Cyclen (adjusted geometric means for C(max), AUC([τ]) and C(min) decreased by 46%, 64% and 82%, respectively) compared with Ortho Cyclen alone. Consistent with NGMN, LNG exposures were decreased 80-86% by efavirenz.

Conclusions: Although efavirenz had no significant effect on the PK of EE, exposures to the progestin components of Ortho Cyclen, NGMN and LNG, were substantially reduced. The results reinforce the need to use reliable methods of barrier contraception, even when taking oral contraceptives and efavirenz.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alkynes
  • Anti-HIV Agents / administration & dosage*
  • Anti-HIV Agents / pharmacokinetics
  • Area Under Curve
  • Benzoxazines / administration & dosage*
  • Benzoxazines / pharmacokinetics
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / pharmacokinetics*
  • Contraceptives, Oral, Synthetic / administration & dosage
  • Contraceptives, Oral, Synthetic / pharmacokinetics
  • Cyclopropanes
  • Drug Interactions
  • Estrogens / administration & dosage
  • Estrogens / pharmacokinetics
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Norgestrel / administration & dosage
  • Norgestrel / analogs & derivatives*
  • Norgestrel / pharmacokinetics
  • Reverse Transcriptase Inhibitors / administration & dosage*
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Young Adult


  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Contraceptives, Oral, Combined
  • Contraceptives, Oral, Synthetic
  • Cyclopropanes
  • Estrogens
  • Reverse Transcriptase Inhibitors
  • Norgestrel
  • Ethinyl Estradiol
  • norgestimate
  • efavirenz