Impact of Generic Substitution of Anticonvulsants on the Treatment of Epilepsy

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Abstract
Two anticonvulsants, namely phenytoin and carbamazepine, are susceptible to bioavailability problems as a result of very low water solubility and a low therapeutic ratio. In addition, phenytoin has nonlinear pharmacokinetics that exaggerate the effects of changes in the fraction of the dose absorbed. There are many published reports of bioinequivalence with different formulations of phenytoin, but fewer with carbamazepine. However, regulatory bodies have developed criteria that have to be satisfied before a new formulation is licensed, and it is therefore considered unlikely that important incidents of bioinequivalence following generic substitution will occur with these drugs in the future. As an overall source of variation in therapeutic response, bioinequivalence is negligible.