There may be subsets of individuals who are at increased risk for seizures with small changes in bioequivalence, such as those who have had life-threatening status epilepticus in the past, pregnant women, people with epilepsy who have been seizure free for many years, and people with other serious medical conditions.
We don't really know what percentage change in AUC or Cmax between products is actually safe—that is, which ranges of bioequivalence translate to therapeutic equivalence and which do not. In his study, Dr. Krauss is suggesting that certain ranges of difference between products should be safe and others perhaps not so safe. Unfortunately, we have no data to support that inference. There are no data providing evidence that 90% confidence intervals in the 80%-125% range, which are the current FDA standard, translate to therapeutic equivalence. The FDA created this range based on expert opinion.
A recent FDA advisory committee indicated that the range for generic AED confidence intervals may not be optimal for patients with epilepsy, but the committee did not agree upon any specific recommendations.
The FDA states that all brand name–to-generic or generic-to-generic switches are safe for all people with epilepsy. I believe the only way to test this is to perform a prospective, randomized study of people with epilepsy.
MICHAEL PRIVITERA, M.D., is a professor of neurology at the University of Cincinnati and is director of the Cincinnati Epilepsy Center. He has received research funding and honoraria for speaking or consulting from UCB, Johnson & Johnson, Pfizer, Eisai, the National Institutes of Health, and the American Epilepsy Society.
