Effect of steady-state etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone☆☆☆★

Abstract 

Background

Etravirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI) active against NNRTI-resistant HIV, is an inducer of CYP3A4 and an inhibitor of CYP2C9/19.

Study Design

The effect of etravirine on the pharmacokinetics and pharmacodynamics of ethinylestradiol and norethindrone was assessed in 30 HIV-negative females.

Following a run-in cycle with ethinylestradiol/norethindrone, the pharmacokinetics of ethinylestradiol and norethindrone was assessed on Day 15 of Cycle 2. Etravirine 200 mg bid was coadministered on Day 1 to Day 15 of Cycle 3, with pharmacokinetic assessments of ethinylestradiol, norethindrone and etravirine on Day 15.

Results

When combined with etravirine, the least-squares means (LSM) ratios (90% confidence interval) for ethinylestradiol AUC_24h, C_max and C_min were 1.22 (1.13–1.31), 1.33 (1.21–1.46) and 1.09 (1.01–1.18), respectively, compared to administration alone. LSM ratios for norethindrone parameters were 0.95 (0.90–0.99), 1.05 (0.98–1.12) and 0.78 (0.68–0.90), respectively.

Conclusion

These changes are not considered clinically relevant. No loss in contraceptive efficacy is expected when coadministered with etravirine.

Keywords: Oral contraceptives, Ethinylestradiol, Norethindrone, TMC125, Etravirine, Non-nucleoside reverse transcriptase inhibitor, Drug–drug interaction, Pharmacokinetics