Real-world effect of a potential drug-drug interaction between topiramate and oral contraceptives on unintended pregnancy outcomes

Abstract

Objective: To evaluate the association of concomitant topiramate and oral hormonal contraceptive use with unintended pregnancies.

Study design: We conducted a retrospective cohort design in MarketScan Research Databases (2005-2018) on women aged 12-48 who had migraines or chronic headaches and concomitantly used topiramate and oral contraceptives. We used a cohort of patients with oral contraceptives and concomitant use of other migraine prevention therapies (propranolol, metoprolol, amitriptyline, venlafaxine, or verapamil) as a comparator. We followed patients for up to 1 year from cohort entry to assess the occurrence of unintended pregnancy (i.e., contraception failure). Pregnancy events were measured via an algorithm harnessing medical encounters information with live births, terminations, or prenatal visits. Statistical models accounted for multiple cohort entries and adjusted for measured confounders via a propensity score weighting method.

Results: We identified 63,649 episodes of oral contraceptives+topiramateand 59,012 episodes of oral contraceptives+other maintenance therapies. The mean age was 29.2±9.0 and 29.0±9.3 years in the study cohorts. In the adjusted analysis, the contraception failure rate (95% confidence interval) was 1.3 (1.1, 1.6) per 100 person-years in the oral contraceptives+topiramate cohort and 1.3 (1.1, 1.6) in the oral contraceptives+other maintenance therapies cohort. The adjusted rate ratio and rate difference measures were 1.00 (0.80, 1.26) and 0.00 (-0.3, 0.3).

Conclusion: Concomitant use of low-dose topiramate and oral contraceptives among patients with migraines was not associated with a higher risk for unintended pregnancies.

Implications: Our real-world findings confirm clinical pharmacology trials, suggesting that low-dose (≤200 mg/d) topiramate may not influence oral contraceptive effectiveness.

Keywords: CYP3A4; Drug interaction; Hormonal contraception; Pharmacoepidemiology; Topiramate; Translational science.