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

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((R)) and with Ortho Tri-Cyclen((R)) 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 mug 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 mug 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([tau])) and 37% in EE lowest plasma concentration (C(min)) compared with EE 35 mug 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((tau)) 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 mug of EE.