Interactions between hormonal contraception and antiepileptic drugs: Clinical and mechanistic considerations

Abstract

Antiepileptic drugs (AEDs) and hormonal contraceptives may affect each other's metabolism and clinical efficacy. Loss of seizure control and unplanned pregnancy may occur when these compounds are used concomitantly. Although a large number of available preparations yield a plethora of possible drug combinations, most of these drug interactions are predictable and, thus, avoidable. Unfortunately, there is a substantial lack of data regarding the newer AEDs. Detailed understanding of these issues is necessary for those who prescribe AEDs and/or hormonal contraception to women with epilepsy, as well as for those who provide comprehensive care, education and counseling to them, in order to reduce the unacceptably high number of unplanned pregnancies among women with epilepsy.

The JAK1 Inhibitor Upadacitinib Has No Effect on the Pharmacokinetics of Levonorgestrel and Ethinylestradiol: A Study in Healthy Female Subjects

“…The estrogen ethinylestradiol and the progestin levonorgestrel are among the most commonly prescribed contraceptives and both are metabolized through CYP3A, sulfotransferases, and uridine 5′‐diphospho‐glucuronosyltransferases . Drugs that have pharmacokinetic interactions with oral contraceptives can potentially result in failure of contraception through induction of metabolism or increased incidence of the side effects through inhibition of metabolism . Given the wide use of hormonal contraceptives, this study was conducted to characterize any potential effect of upadacitinib on ethinylestradiol and levonorgestrel pharmacokinetics to inform safety of coadministration in patients.…”

Practice Guideline: Contraception for Adolescents with Chronic Illness

“…Specific anti-epileptic drugs induce liver enzymes and diminish contraceptive efficacy. The following anti-epileptic drugs do not appear to interact with hormonal birth control: gabapentin, levetiracetam, zonisamide, lacosamide, and topiramate (if dose < 200 mg; Reimers, Brodtkorb, & Sabers, 2015).…”

Establishing a Multidisciplinary Framework to Study Drug‐Drug Interactions of Hormonal Contraceptives: An Invitation to Collaborate

“…For example, some anti‐epileptic drugs, such as carbamazepine, felbamate, or phenytoin (perpetrators), may induce cytochrome P450 (CYP)3A4 and, hence, increase the clearance of HCAs (victims). Therefore, women with epilepsy taking HCAs are at particular risk for DDIs . When used properly, HCA failure is 1% in healthy women but it is 3–6% in women with epilepsy .…”

“…Therefore, women with epilepsy taking HCAs are at particular risk for DDIs . When used properly, HCA failure is 1% in healthy women but it is 3–6% in women with epilepsy . Although, in the past, studies and recommendations on the interaction between HCAs and anti‐epileptic drugs have often focused on the alteration of the estrogen component of the agents, it has now become clear that it is, in fact, the progestin component that provides the major part of the contraceptive effect of modern combined oral contraceptives .…”

“…Such understanding is hampered by the fact that many of the HCAs were developed > 50 years ago with different standards of clinical trial development compared to today, so that knowledge gaps on the metabolic pathways of progestins and ethinyl estradiol remain, albeit this could be tackled in part by conducting in vitro experiments. As a consequence, our knowledge on the potential for pharmacokinetic (PK; or pharmacodynamic (PD)) DDIs with HCAs is incomplete . The use of model‐informed drug development and discovery approaches including physiologically based pharmacokinetic (PBPK) and model‐based meta‐analysis (MBMA) can offer integrated assessment to bridge these gaps.…”