Comparison of contraceptive failures associated with CYP3A4-inducing drug-drug interactions by route of hormonal contraceptive in an adverse event reporting system

ABSTRACT Objective : To estimate associations between contraceptive failures and concomitant CYP3A4-inducing medications by route of administration. Study Design : Comparison of unintended pregnancy outcomes within U.S. Food and Drug Administration's Adverse Event Reporting System by co-use of CYP3A4-inducing drugs and route of administration for levonorgestrel and etonogestrel/desogestrel. Results : Among 14,504 levonorgestrel case reports, the reporting odds ratio (ROR) was increased for oral (ROR=4.2[3.0-5.7]), implants (ROR=8.0 [5.8-11.0]), but not intrauterine (ROR=0.9[0.6-1.3]) levonorgestrel products. For 9,348 etonogestrel/desogestrel case reports, oral and vaginal products were not associated with contraceptive failure. Etonogestrel containing implants (ROR=4.9 [4.1-5.9]) were associated with increased contraceptive failure. Conclusion : Levonorgestrel containing combination oral products and implants containing levonorgestrel or etonogestrel were prone to CYP3A4-inducing drug-drug interactions that may increase contraceptive failures.