Antiseizure medications and oral contraceptives: Impact of enzyme inducers on pregnancy outcomes and costs

Purpose: To show the impact of drug-drug interactions (DDIs) associated with co-administration of enzyme-inducing (EI) antiseizure medications and oral contraceptives (OCs) on the annual number of unintended pregnancies, their outcomes, and their associated costs in the United States (US). Methods: A Microsoft Excel pregnancy-outcomes model was developed to determine the impact of DDIs in women who take an OC as well as an EI antiseizure medication known to lower the effectiveness of the OC in preventing pregnancy. The model compared the number of unintended pregnancies, the expected pregnancy outcomes, and associated costs in women taking an OC and an EI medication with a matched cohort of women who took an OC and an enzyme-neutral (EN) antiseizure medication that is known not to interact with OCs. The model perspectives were patients and third-party payers in the US. Unintended pregnancy rates, pregnancy outcomes, and cost inputs for the model were taken from published studies. Results: The results of the analysis showed an estimated increase in the annual number of unintended pregnancies in the US of 503 (a change from 1151 to 1654), an increase of 44.7%, for the estimated 71,922 women currently taking an OC plus an EI medication in the US when compared with a matched cohort taking an OC plus an EN medication. This resulted in an estimated annual healthcare cost increase of $3 million, which is an increase of 5.5% in the annual costs for contraception and pregnancy care. A scenario analysis showed that the annual number of unintended pregnancies could be lower (575 vs 1654) for a matched cohort of women taking EI medications and using a copper intrauterine device, a highly effective and nonhormonal form of contraception, rather than an OC. Conclusions: Physicians treating women of reproductive age for epilepsy who wish to avoid pregnancy should consider the potential for DDIs that might result in unintended pregnancies. Thus, physicians should alert women using EI medications for epilepsy control to the increased potential for unintended pregnancies if they use OCs for contraception. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).