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

• Published in: Antiviral therapy 2011-01, Vol.16 (2), p.157-164
• Main Authors: ZHANG, Jenny, CHUNG, Ellen, YONES, Cynthia, PERSSON, Anna, MOHNKE, Lisa, ELEY, Timothy, XIAOHUI XU, BERTZ, Richard
• Format: Article
• Language: English
• Subjects: Adult; Anti-HIV Agents - administration & dosage; Anti-HIV Agents - pharmacokinetics; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Atazanavir Sulfate; Biological and medical sciences; Contraceptives, Oral, Combined - administration & dosage; Contraceptives, Oral, Combined - pharmacokinetics; Drug Interactions; Drug Therapy, Combination; Ethinyl Estradiol - administration & dosage; Ethinyl Estradiol - pharmacokinetics; Female; Humans; Medical sciences; Middle Aged; Norgestrel - administration & dosage; Norgestrel - analogs & derivatives; Norgestrel - pharmacokinetics; Oligopeptides - administration & dosage; Oligopeptides - pharmacokinetics; Pharmacology. Drug treatments; Pyridines - administration & dosage; Pyridines - pharmacokinetics; Ritonavir - administration & dosage; Ritonavir - pharmacokinetics; Women's Health; Young Adult
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP1724

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. 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. 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. 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.