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

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 couse 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 9348 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. IMPLICATIONS: The progestin components of hormonal contraceptives are susceptible to drug-drug interactions, but this susceptibility is influenced by route of administration. This study provides evidence from an Adverse Event Reporting System that CYP3A4-inducing medications increase the risk of unintended pregnancy for oral and implant contraceptives but not intrauterine or vaginal devices.