Brand-Name Versus Generic AEDs: Are They Really Any Different?

Summary and Comment |
October 4, 2011

Brand-Name Versus Generic AEDs: Are They Really Any Different?

  1. Robert C. Knowlton, MD, MSPH

Analysis of bioequivalence studies suggests that switching between brand-name and generic antiepileptic drugs is relatively safe but that generic-to-generic switching might increase the risk for adverse effects.

  1. Robert C. Knowlton, MD, MSPH

A major concern for epilepsy patients and their caregivers is the switch from brand-name antiepilepsy drugs (AEDs) to generic formulations. Switching to or starting on generic AEDs has become mandatory for the vast majority of epilepsy patients in the U.S., since nearly all the newer-generation AEDs are now available in generic formulations. These authors analyzed bioequivalence studies required for Abbreviated New Drug Applications submitted to the FDA, obtained via Freedom of Information Act requests, to answer the central question of whether generic AEDs are accurate copies of brand-name drugs. They also addressed whether switches between generic formulations are safe and effective.

Data from 141 generic formulations of the following AEDs were analyzed: carbamazepine, divalproex, gabapentin, lamotrigine, topiramate, levetiracetam, oxcarbazepine, and zonisamide. Between generic and brand-name formulations, total drug concentration differences were less than 15% for nearly all bioequivalence studies (98.8%). Peak drug concentrations differed more — by 15% to 25% in 10.85% of studies. Variability in distributions for both measures was similar between formulations. Because generic–generic switches were not studied, the authors conducted simulation studies of all possible generic substitutions for other generic AEDs. In these simulations, total drug concentrations differed by 15% to 25% for 14.3% of the comparisons, and peak drug concentrations differed by that much for 35.1% of the comparisons. (The other comparisons showed smaller differences.) The authors conclude that total drug delivery for generic carbamazepine, divalproex, and newer-generation AEDs is comparable to reference brand-name drugs, but that substitutions between generic AEDs may not be well-tolerated by some patients.

Comment

These findings are very important because they should at least begin to put to rest what has at times been a contentious debate about the safety and efficacy of relatively inexpensive generic substitutes for brand-name epilepsy drugs. However, the study findings also show that another concern about generic AEDs is valid: The variation in generic–generic substitutions is potentially significant. Simulations of these substitutions reveal that a substantial minority of patients might experience adverse effects from a relatively large variation in peak drug concentrations if numerous generic formulation changes occur. The data do not indicate any clear risk for “breakthrough” seizures from switching between generics. The findings may not apply to children or to older populations, who were not subjects in most of the bioequivalence studies. Because of the potential risk for altered effectiveness with generic–generic switches, patients, their caregivers, or their physicians may want to ask their pharmacies to maintain generic formulation consistency as much as possible.

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