Are there potential problems with generic substitution of antiepileptic drugs?: A review of issues

SummaryIn response to increasing cost pressures, healthcare systems are encouraging the use of generic medicines. This review explores potential problems with generic substitution of antiepileptic drugs (AEDs).A broad search strategy identified approximately 70 relevant articles. Potential problems with generic substitution included:
• potentially serious consequences of failure of therapy, particularly in well-controlled patients;
• potential for adverse events and variability of response to AEDs;
• need for careful titration and dosing of AEDs and susceptibility of some patients to develop problems, even with small changes in drug levels;
• bioequivalence, as defined by regulatory bodies, may not correspond to therapeutic equivalence for AEDs, because of the permitted range of bioavailability for generics, evaluation methods that use small numbers of relatively young healthy volunteers and individual variation;
• potential for problems from poor continuity of supply;
• cost savings may be outweighed by the cost of adverse consequences;
• potential medico-legal consequences in patients who did not give informed consent to switching of AEDs.The limited evidence (mainly case reports with some pharmacokinetic studies) appears to support these concerns for older AEDs. As a result, restrictions on use of specific generic AEDs are in place in some countries and recommended by some lay epilepsy organisations.As more AEDs lose patent protection, it is important to examine the question of whether generic substitution may pose problems for patients with epilepsy, and whether there should be safeguards to ensure that both physician and patient are informed when generic substitution occurs.