Continuous low dose use of the anticonvulsant medication topiramate and oral contraceptives is not associated with increased risk of unintended pregnancy among patients with migraines, according to a recent study.
Worldwide, family planning is often managed using hormonal contraceptives, many of which are taken in oral dosage forms. Contraception failure refers to unintended pregnancy while on treatment and is linked to potential significant emotional and health consequences.
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Factors such as smoking, treatment adherence, obesity, and potential drug-drug interactions impact the efficacy of hormonal contraceptives. These products achieve hepatic metabolism through the CYP3A4 enzyme family, making them susceptible to enzyme-inducing agents.
Patients with epilepsy management and migraine prophylaxis may use topiramate, a moderate CYP3A4 enzyme inducer, for treatment. Preventing unintended pregnancy is critical for topiramate use, making drug-drug interactions between topiramate and hormonal contraceptives likely.
To determine the association between topiramate and oral hormonal contraceptive use with unintended pregnancies, investigators conducted a retrospective cohort design using MarketScan Research Databases, a private health insured database. Data from 2005 to 2018 on medical and pharmacy encounters was included in the database.
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Patients aged 12 to 48 years with diagnoses of migraines or chronic headaches were included in the analysis. Participants mainly had a daily topiramate dose of 200 mg or less, which is considered low dose topiramate.
Exclusion criteria included infertility, hirsutism, ovary dysfunctions, and not having continuous insurance eligibility at least 6 months before the reference date.
Drug use periods were measured using prescription dispensing data and “days of supply” information. Patients with overlapping days of oral contraceptive and topiramate supplies made up a concomitant use cohort. At least 14 days of use was seen in this cohort.
Patients also had at least 2 medical claims of migraine or chronic headache in the 6 months before entering the study. The topiramate cohort was compared with a cohort consisting of metoprolol, propranolol, venlafaxine, amitriptyline, and verapamil users.
Contraceptive failure was the primary outcome of the study, identified through a pregnancy identification algorithm. The pregnancy start date was not reported, but medical encounters for pregnancy end point and prenatal visits were used to determine pregnancy.
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There were 63,649 cases of combined contraceptive and topiramate use, 95% of which took low topiramate daily. There were also 59,012 cases of oral contraceptive use alongside other maintenance therapies. Patients were aged a mean 29.2 years in the topiramate group and 29 years in the other maintenance therapies group.
Similar demographics and comorbidities were reported between the 2 groups. The other maintenance therapies group saw a higher rate of hypertension, at 10.9% compared to 5.9% in the topiramate group.
There were 158 pregnancies identified in the topiramate group and 144 in the other maintenance therapies group. Both groups had a contraception failure rate of 1.3 per 100 person-years, with a rate difference of 0.02.
No rate difference was observed between the 2 groups in the adjusted analysis. This indicates low dose topiramate will not affect oral contraceptive efficacy, but investigators noted differing between strong and moderate CYP3A4 induction effects could better inform prescribing choices.
Reference
Sarayani A, Winterstein A, Cristofoletti R, Vozmediano V, Schmidt S, Brown J. Real-world effect of a potential drug-drug interaction between topiramate and oral contraceptives on unintended pregnancy outcomes. Contraception. 2023;120. doi:10.1016/j.contraception.2023.109953
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