The hazards and problems of generic substitutions for antiepileptic drugs are reviewed in a Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology [1] and are discussed by Nuwer MR et al [2]. According to the present Federal guidelines for manufacturers a generic product may be approved as equivalent to a brand name product even if it produces widely varying bioavailability in some individuals. Implicit in the FDA guidelines is the assumption that a ± 20% change in mean steady-state serum concentration of antiepileptic drugs can be tolerated safely. However, there is no scientific evidence to support this assertion. When substitution of different formulations of an antiepileptic drug occurs, the patient is put at risk of drug intoxication or breakthrough seizures. Generic substitution of drugs such as phenytoin and carbamazepine which have a narrow therapeutic range is especially problematic.
COMMENT. Economic benefits because of lower cost of generic substitutions may be outweighed by the need for more frequent serum concentration determinations and costs of follow-up visits.