Impact of generic substitution of anticonvulsants on the treatment of epilepsy.

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.However, generic substitution may cause confusion and anxiety in patients' minds when it occurs without prior warning. These effects can be allayed by information given by prescribing physicians, pharmacists and patient organisations.Given a positive approach to the issues that arise, the financial benefits of generic prescribing can be enjoyed by patients and by healthcare systems. The pharmaceutical industry should be expected to meet the challenge of fair competition in trading.