Switching the manufacturer of antiepileptic drugs is associated with higher risk of seizures

Objective

Despite bioequivalence, the exchangeability of antiepileptic drugs in clinical settings is disputed. Therefore, we investigated the risk for recurrent seizures after switching the manufacturer of the same drug in a large German cohort.

Methods

Anonymous patient data from practice neurologists throughout Germany between 2011 and 2016 were collected using the IMS Disease Analyzer database (QuintilesIMS, Frankfurt, Germany). People with epilepsy were included if at least 2 prescriptions within 360 days and 1 within 180 days prior to the index date were available. The cohort was separated into a seizure group and seizure‐free controls. Both groups were matched 1:1 according to age, gender, insurance status, and treating physician. The risk for breakthrough seizures after a manufacturer switch of the same antiepileptic drug was analyzed using multivariate regression models.

Results

A total of 3,530 people with epilepsy were included (each group, n = 1,765; age = 53.7 ± 19.8 years). Patients with seizures had switched the drug manufacturer more often than controls (26.8% vs 14.2%; odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.08–1.69, p = 0.009), both from branded to generic (5.5% vs 2.4%; OR = 1.85, 95% CI = 1.30–2.64, p < 0.001) and between generic drugs (14.7% vs 7.1%; OR = 1.45, 95% CI = 1.13–1.87, p = 0.004).

Interpretation

In previously seizure‐free patients, switching the manufacturer of antiepileptic medications was associated with a higher risk for seizure recurrence. Our retrospective approach does not allow us to determine whether other changes in medical care at the same time could contribute to the recurrence. However, it would be prudent to avoid switching the manufacturer of anticonvulsants in seizure‐free patients.