Risky ASM-Contraceptive Co-prescribing Still Common

Nearly one third of women with epilepsy prescribed a hormonal contraceptive also had overlapping prescriptions for an enzyme-inducing anti-seizure medication (ASM) that could reduce the efficacy of the birth control, increasing the risk for unintended pregnancy, new research suggested.Laura Kirkpatrick, MD, MSThe findings are surprising, given well-established evidence that the drug combination can reduce the efficacy of this form of birth control, said lead investigator Laura Kirkpatrick, MD, MS, assistant professor of pediatrics and neurology at the University of Pittsburgh School of Medicine in Pittsburgh.In a retrospective cohort study of more than 20,000 women with epilepsy of reproductive age, 32.6% of those prescribed hormonal contraceptives had at least 14 days of overlap with an enzyme-inducing ASM known to affect contraceptive efficacy. Among those with overlap, the median duration was about 7 months.Researchers also found that overlapping prescriptions were more common among those with intellectual disability or drug-resistant epilepsy (DRE).“I was surprised by how many people with epilepsy may be at risk for contraceptive failure,” Kirkpatrick told Medscape Medical News. “Contraception is very important in people with epilepsy to prevent unplanned pregnancy when desired.”The study was published online on October 7 in Neurology.Drug Interaction ConcernsPreventing unplanned pregnancy is important for people with epilepsy, given the potential risks for seizures during pregnancy and fetal risks associated with some ASMs.Studies show that certain enzyme-inducing ASMs can increase the breakdown of hormones used in some contraceptives, potentially reducing their effectiveness. Birth control types affected include combined oral contraceptives, progestin-only pills, patches, vaginal rings, and subdermal implants. Hormonal and copper intrauterine devices (IUDs) are not affected by these kinds of ASMs.The US Medical Eligibility Criteria classifies combined hormonal contraceptives and progestin-only pills used with enzyme-inducing ASMs as category 3, meaning the risks generally outweigh the benefits. However, subdermal implants are classified as category 2. Despite these recommendations, previous research has shown that clinicians may not always recognize these potential drug interactions. A 2022 survey published in Epilepsy & Behavior showed gaps in neurologists’ knowledge of ASM-contraceptive interactions. In 35% of responses, neurologists incorrectly identified which ASM could interact with hormonal contraception.To learn more about how often these potentially interacting medications are co-prescribed in patients with epilepsy, researchers analyzed data on 110,976 women aged 12-51 years with epilepsy (median age, 24 years; 54.8% White) who were enrolled in Medicaid from 2016 to 2021. Of the full cohort, 21,923 were prescribed a hormonal contraceptive that could interact with enzyme-inducing ASMs between 2018 and 2021.Prescriptions were considered to overlap when a hormonal contraceptive and an enzyme-inducing ASM were prescribed at the same time for at least 14 days. The enzyme-inducing ASMs included carbamazepine, cenobamate, clobazam, eslicarbazepine, felbamate, oxcarbazepine, perampanel, phenobarbital, phenytoin, primidone, rufinamide, and topiramate.Prolonged Overlap CommonAmong women prescribed a hormonal contraceptive, 32.6% also had overlapping prescriptions for an enzyme-inducing ASM during the study period. This occurred with 33.4% of combined oral contraceptives, 29.6% of progestin-only pills, 27.5% of implants, 24.1% of patches, and 19.1% of vaginal rings.When the prescriptions overlapped, 61.9% of patients were prescribed the contraceptive first, while 38.1% started the enzyme-inducing ASM first. The overlap lasted a median of 218 days, or about 7 months.Patients with intellectual disability had more than twice the odds of experiencing an overlap (adjusted odds ratio [aOR], 2.33), as did those with DRE (aOR, 1.73). Women aged 35 years or older also had higher odds of overlap than those aged 19-34 years (aOR, 1.45).Intellectual disability was also associated with more contraceptive days overlapping with an enzyme-inducing ASM (OR, 2.27), while DRE was associated with a smaller increase in overlap (OR, 1.27). Those aged 35 years or older also had more overlap days (OR, 1.51).Study limitations included the use of claims data, which did not show whether women actually took the prescribed medications, received counseling about potential interactions, or experienced contraceptive failure.Unnoticed Potential InteractionsThe prolonged overlap between contraceptive and enzyme-inducing ASM prescriptions was one of the study’s notable findings, Kirkpatrick said, noting that the duration suggests these medication combinations may not be addressed quickly.“The combination of medications isn’t a transient phenomenon that is rapidly being addressed or corrected. Most likely, the drug interactions are going unrecognized for prolonged periods of time,” she said. “It’s also possible that the medications are being used together intentionally, but this possibility seems less likely to me.”The findings also raise questions about why these medications are prescribed together, particularly among people with DRE.“I think people with drug-resistant epilepsy often require multiple strong medications to treat their epilepsy, and at times drug interactions with other medications might be overlooked,” Kirkpatrick said.The investigators plan to use the same data set to examine pregnancy rates among people prescribed interacting medications. They also plan to conduct qualitative research with clinicians and patients to better understand why they make these prescribing decisions. “Is it simply a matter of lack of knowledge of the drug interaction, or are these medications being used together on purpose for some reason?” Kirkpatrick said.Don’t Overlook ContraceptionWhen an enzyme-inducing ASM is necessary, clinicians should consider contraceptive methods that are not affected by these medications, including IUDs, which are highly effective and have minimal systemic drug interactions, Trudy D. Pang, MD, assistant professor of neurology at Harvard Medical School in Boston, told Medscape Medical News.Trudy D. Pang, MD“The choice should be individualized through shared decision-making, taking into account reproductive goals, patient preference, and medical comorbidities,” said Pang, who is also the director of the Clinical Neurophysiology and Adult Epilepsy Fellowship at Beth Israel Deaconess Medical Center in Boston.Contraception and family planning should be part of routine epilepsy care, Pang said, with potential interactions reviewed whenever an ASM or hormonal contraceptive is started or changed.Alexa M. King, MD, assistant professor of neurology at Feinberg School of Medicine in Chicago, echoed the importance of ongoing counseling.“Ideally, counseling about the potential interaction of ASMs and contraception should occur early and often to empower patients to be aware of these interactions,” she told Medscape Medical News.For patients who cannot or do not want to use an IUD, King recommended discussing additional contraceptive protection.“If an intrauterine device is not an option, then counseling about using a backup barrier method of contraception in addition to a susceptible hormonal method should be done,” said King, who is also the director of the Women’s Epilepsy Program at Northwestern Medicine in Chicago.The choice of contraception may also change as reproductive goals shift over time, she added.“Counseling about reproductive goals and these interactions should continue throughout the subsequent visits with the patient,” King said.Disclosure information for study authors is available in the original study publication.