Switching to Generic Levetiracetam Associated With Minimal Impact on Seizure Frequency

Replacing brand-name levetiracetam, a broad-spectrum antiepileptic drug (AED), with a generic version is associated with a minimal increase in seizure frequency among patients with focal and general epilepsy, according to findings from a retrospective study.

“Generic prescription substantially reduces the costs of treatment and plays an important role in patient adherence due to the lower price compared to that of branded products,” the researchers, led by Lee Gha-Hyun, of the Pusan National University School of Medicine in Busan, the Republic of Korea, wrote. “Clinicians are concerned about substituting AEDs, especially in well-controlled patients, as even a single breakthrough seizure may have severe financial and social consequences, such as loss of driving license, loss of employment, and/or injuries.”

Epilepsy patients receiving levetiracetam treatment and care from a tertiary outpatient epilepsy clinic were included in the analysis (n = 148). Patients had been taking the drug for ≥6 months and converted to generic levetiracetam during the study period. Study investigators analyzed data from individual patient medical records from 6 months prior and 6 months after the generic substitution. The variables included in the analysis included increases in seizure frequency, defined as a ≥50% increase in seizures following conversion date, and seizure freedom, or the achievement of a seizure-free status during and after the 6-month conversion date.

Approximately 6 months prior to generic substitution, 73.6% (n = 109) of patients had achieved seizure freedom. Seizure-free status was maintained in 96.3% (n = 105) of patients, with seizures occurring in 3.7% (n = 4) of patients approximately 6 months after generic conversion. Up to 8 patients out of 39 who had seizures prior to conversion attained seizure-free status 6 months after substitution.

At baseline, the median seizure frequency prior to conversion was 0 (interquartile range, 0-1). Approximately 1.5% (n = 1) of patients on levetiracetam monotherapy at baseline had a documented increase in seizure frequency after generic substitution. Conversely, 3.0% (n = 2) of patients experienced a reduction in frequency. More patients with focal epilepsy experienced an increase in seizure frequency compared with those with generalized epilepsy (6 vs 1, respectively), and each patient who experienced a decrease in seizure frequency had a documented diagnosis of focal epilepsy.

Younger age was associated with significantly greater reductions in seizure frequency following generic substitution (P = .035). Additionally, those with decreased seizure frequency had significantly more seizures prior to generic conversion than those with seizure frequency that was unchanged (P <.001).

Considering patients in this study had epilepsy that was adequately controlled, the findings may not generalize to patients with poorly controlled disease. The researchers also wrote, “Several confounding factors could contribute to a change in seizure frequency that mimics a breakthrough seizure…[and] the group sizes in this study may have been insufficient to show a significant effect.”

The study, “Brand name to generic substitution of levetiracetam in patients with epilepsy,” was published in Seizure.