• drug–drug interaction;
  • ethinyl estradiol;
  • HIV-1;
  • oral contraceptive;
  • raltegravir


• Oral contraceptives are a widely prescribed means of birth control that requires the maintenance of adequate pharmacokinetics of the active components to maintain efficacy.

• Oral contraceptive use in HIV-infected women is widespread and may often occur in women receiving raltegravir as part of their antiretroviral therapy.

• Given the prevalence of oral contraceptive use and likely need for co-administration with raltegravir, combination administration should be studied to assess the safety and the pharmacokinetics of the oral contraceptive components.


• This study is the first to provide the practitioner with a detailed description of the influence of raltegravir on the pharmacokinetics of a triphasic oral contraceptive.

• This study demonstrates that raltegravir does not meaningfully alter the pharmacokinetics of the estrogen or progestin components of such oral contraceptives.

• This paper provides confidence to the practitioner that there will be no clinically meaningful interaction that would preclude the concurrent use of raltegravir and such oral contraceptives in combination.

AIMS Oral contraceptives such as norgestimate–ethinyl estradiol (Ortho Tri-Cyclen®) are commonly prescribed in the HIV-infected patient population. A placebo-controlled, randomized, two-period crossover study in healthy HIV-seronegative subjects was conducted to assess the effect of raltegravir on the pharmacokinetics of the estrogen and progestin components of norgestimate–ethinyl estradiol [ethinyl estradiol (EE) and norelgestromin (NGMN), an active metabolite of norgestimate (NGT)].

METHODS In each of two periods, nineteen healthy women established on norgestimate–ethinyl estradiol contraception (21 days of active contraception; 7 days of placebo) received either 400 mg raltegravir or matching placebo twice daily on days 1–21. Pharmacokinetics were analysed on day 21 of each period.

RESULTS The geometric mean ratio (GMR) and 90% confidence interval (CI) for the EE component of norgestimate–ethinyl estradiol when co-administrated with raltegravir relative to EE alone was 0.98 (0.93–1.04) for the area under the concentration–time curve from 0 to 24 h (AUC0–24 h) and 1.06 (0.98–1.14) for the maximum concentration of drug in the plasma (Cmax); the GMR (90% CI) for the NGMN component of norgestimate–ethinyl estradiol when co-administered with raltegravir relative to NGMN alone was 1.14 (1.08–1.21) for AUC0–24 h and 1.29 (1.23–1.37) for Cmax. There were no discontinuations due to a study drug-related adverse experience, nor any serious clinical or laboratory adverse experience.

CONCLUSIONS Raltegravir has no clinically important effect on EE or NGMN pharmacokinetics. Co-administration of raltegravir and an oral contraceptive containing EE and NGT was generally well tolerated; no dose adjustment is required for oral contraceptives containing EE and NGT when co-administered with raltegravir.