Center for Drug Evaluation and Safety, Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, FL, United States; Showa University, School of Pharmacy, Tokyo, Japan.
Center for Pharmacometrics and Systems Pharmacology, Department of Pharmaceutics, University of Florida College of Pharmacy, Orlando, FL, United States.
Contraception. 2021 Apr;103(4):222-224. doi: 10.1016/j.contraception.2020.12.002. Epub 2020 Dec 17.
To estimate associations between contraceptive failures and concomitant CYP3A4-inducing medications by route of administration.
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.
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.
Levonorgestrel containing combination oral products and implants containing levonorgestrel or etonogestrel were prone to CYP3A4-inducing drug-drug interactions that may increase contraceptive failures.
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.
评估通过给药途径与避孕失败相关的同时使用 CYP3A4 诱导药物的情况。
通过美国食品和药物管理局不良事件报告系统，比较依 CYP3A4 诱导药物和给药途径使用左炔诺孕酮和依托孕烯/去氧孕烯的情况下，非意愿妊娠结局。
在 14504 例左炔诺孕酮报告病例中，口服（OR=4.2[3.0-5.7]）、植入（OR=8.0[5.8-11.0]）左炔诺孕酮产品的报告比值比（ROR）增加，但宫内（OR=0.9[0.6-1.3]）左炔诺孕酮产品无此关联。在 9348 例依托孕烯/去氧孕烯报告病例中，口服和阴道产品与避孕失败无关。含依托孕烯的植入物（OR=4.9[4.1-5.9]）与避孕失败风险增加相关。
含左炔诺孕酮的复方口服产品和含左炔诺孕酮或依托孕烯的植入物易发生 CYP3A4 诱导的药物-药物相互作用，可能增加避孕失败的风险。
激素避孕药的孕激素成分易发生药物-药物相互作用，但这种易感性受给药途径的影响。本研究从不良事件报告系统提供了证据，表明 CYP3A4 诱导药物增加了口服和植入避孕药而非宫内或阴道装置的意外怀孕风险。
