The effect of atazanavir/ritonavir on the pharmacokinetics of an oral contraceptive containing ethinyl estradiol and norgestimate in healthy women

Antivir Ther. 2011;16(2):157-64. doi: 10.3851/IMP1724.


Background: Coadministration of oral contraceptives with protease inhibitors is complicated by drug interactions. An open-label three-period single-sequence study assessed the effect of coadministration of atazanavir (ATV)/ritonavir (RTV) with Ortho Tri-Cyclen(®) and with Ortho Tri-Cyclen(®) LO (Ortho-McNeil-Janssen Pharmaceuticals, Inc., Raritan, NJ, USA) on the pharmacokinetics (PK) of ethinyl estradiol (EE), norgestimate (NGM), ATV and RTV.

Methods: A total of 20 healthy women aged 18-45 years received study treatments. In the lead-in period and in period 1, participants received a full cycle of Ortho Tri-Cyclen (EE 35 μg with NGM 0.18/0.215/0.25 mg) from days 1-28. In period 2, participants received a full cycle of Ortho Tri-Cyclen LO (EE 25 μg with NGM 0.18/0.215/0.25 mg) plus ATV/RTV (300/100 mg once daily) on days 29-42. PK assessments were performed on days 14 and 42 in periods 1 and 2, respectively.

Results: ATV/RTV with dose-normalized EE/NGM resulted in geometric mean reductions of 16% in EE peak plasma concentration (C(max)), 19% in EE area under the concentration-time curve for a dosing interval (AUC([τ])) and 37% in EE lowest plasma concentration (C(min)), compared with EE 35 μg with NGM in the absence of ATV/RTV. NGM with EE and ATV/RTV 300/100 mg once daily resulted in increases of approximately 68%, 85% and 102% in 17-deacetyl NGM C(max), AUC((τ)) and C(min), respectively. Two participants discontinued the study because of adverse events.

Conclusions: ATV/RTV with Ortho Tri-Cyclen was well-tolerated and reductions in EE were not predicted to decrease contraceptive efficacy if the formulation contained ≥30 μg of EE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Anti-HIV Agents / pharmacokinetics*
  • Atazanavir Sulfate
  • Contraceptives, Oral, Combined / administration & dosage
  • Contraceptives, Oral, Combined / pharmacokinetics*
  • Drug Combinations
  • Drug Interactions
  • Drug Therapy, Combination
  • Ethinyl Estradiol / administration & dosage
  • Ethinyl Estradiol / pharmacokinetics*
  • Female
  • Humans
  • Middle Aged
  • Norgestrel / administration & dosage
  • Norgestrel / analogs & derivatives*
  • Norgestrel / pharmacokinetics
  • Oligopeptides / administration & dosage
  • Oligopeptides / pharmacokinetics*
  • Pyridines / administration & dosage
  • Pyridines / pharmacokinetics*
  • Ritonavir / administration & dosage
  • Ritonavir / pharmacokinetics*
  • Women's Health
  • Young Adult


  • Anti-HIV Agents
  • Contraceptives, Oral, Combined
  • Drug Combinations
  • Oligopeptides
  • Pyridines
  • norgestimate, ethinyl estradiol drug combination
  • Norgestrel
  • Ethinyl Estradiol
  • Atazanavir Sulfate
  • norgestimate
  • Ritonavir