Simeprevir versus Ethinyl Estradiol/Norethindrone
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Study Design
Interactions between simeprevir and ethinylestradiol/norethindrone were evaluated in an open-label study of 18 healthy female subjects. Subjects received ethinylestradiol/ norethindrone (35 lg/1 mg) for two consecutive 28-day oral contraceptive cycles (21 days of the drug, followed by a 7-day drug-free period). During the second cycle (days 29–56), subjects also received simeprevir (150 mg once daily) for the last 10 days of ethinylestradiol/norethindrone treatment (days 40–49; all treatments were taken under fed conditions). Serum hormone levels for progesterone, follicle-stimulating hormone and luteinizing hormone were also evaluated in this study.
Study Results
The Cmin and AUC24h for ethinylestradiol were similar with coadministration of simeprevir in comparison with ethinylestradiol/norethindrone alone [although the 90 % confidence interval (CI) for the AUC24h ratio of test to reference did not include 1]; the Cmax was 18 % higher with coadministration. The Cmax and AUC24h values for norethindrone were similar with coadministration of simeprevir in comparison with ethinylestradiol/ norethindrone alone (although the 90 % CI for the AUC24h ratio of test to reference did not include 1); the Cmin was 24 % higher with coadministration. These differences are unlikely to be clinically relevant. Coadministration of simeprevir did not yield differences in these levels of progesterone, follicle-stimulating hormone, or luteinizing hormone, in comparison with ethinylestradiol/ norethindrone alone.
Drug Effect on PK PK Parameters
Cmax AUC Cmin
Simeprevir NA NA NA NA
Ethinyl Estradiol No change 1.18 (1.09 – 1.14) 1.12 (1.05 – 1.2) 1 (0.89 – 1.13)
Norethindrone No change 1.06 (0.99 – 1.14) 1.15 (1.08 – 1.22) 1.24 (1.13 – 1.35)
Study Conclusions
The authors concluded that there were no clinically significant changes in pharmacokinetics of ethinyl estradiol or noethindrone when coadministered with simeprevir. Ethinylestradiol/norethindrone may be used in combination with simeprevir without dose adjustment.
References
Ouwerkerk Mahadevan S, Snoeys J, Peeters M, Beaumont Mauviel M, Simion A. Drug–drug interactions with the ns3/4a protease inhibitor simeprevir. Clinical Pharmacokinetics. 2016; 2: 197-208.
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