Clinical drug drug interactions between antiepileptic drugs and hormonal contraceptives: pharmacist considerations

Objective: More than 50 years ago hormonal contraceptive agents (HCAs) were introduced and are used by 100 million women. However, investigation of the effects of antiepileptic drugs (AEDs) is lacking. The objective of this study was to provide a comprehensive review of the evidence on the relationship between antiepileptic use and hormonal contraceptive failure. Methods: A systematic review concerning HCAs and AEDs was performed, 2000-2019, using PubMed. PRISMA guidelines were used to document key search terms. Outcomes were categorized into: effectiveness of therapy, toxicity, and pharmacokinetics. The selected articles were summarized by year, author, title, design, methods, findings, and source. Articles were graded using the Oxford for Evidence-based Medicine scale. Preliminary Results: Thirteen articles met the inclusion criteria. An interaction between AEDs and the combined oral contraceptive pill was first proposed when estradiol was reduced from 100 to 50 microg. Studies report a higher incidence of breakthrough bleeding and contraceptive failure among women with epilepsy. Phenobarbital, phenytoin, carbamazepine, oxcarbazepine, felbamate and topiramate have been shown to increase the metabolism of ethinylestradiol and progestogens. There were no studies showing an interaction between the combined oral contraceptive pill, progesterone-only pill, medroxyprogesterone injections or levonorgestrel implants and the AEDs valproic acid, vigabatrin, lamotrigine, gabapentin, tiagabine, levetiracetam, zonisamide, ethosuximide and benzodiazepines. Conclusions: Considerations for pharmacists when counseling women taking AEDs: preparation containing at least 50 microg of ethinylestradiol is needed. This is an important study as access for HCAs expands. Eight states and D.C. allow pharmacist HCA prescribing.