Recommendations of the Italian League against Epilepsy working group on generic products of antiepileptic drugs.
The availability of generic products of antiepileptic drugs (AEDs) has been increasing in recent years. In view of the importance of the issue, the Italian League against Epilepsy (LICE) set up an ad hoc working group whose task was to assess available evidence on the efficacy and safety of generic AEDs in the treatment of epilepsy and to produce recommendations on their use. A careful review of the literature revealed no adequately powered randomized controlled trials that assessed the risk/benefit ratio of generic substitution. Although there have been reports of loss or worsened seizure control, or appearance of adverse events, following the switch from brand products to generics, a critical assessment of the evidence generally does not allow us to establish a cause-effect relationship between the switch and a change in clinical status. Overall, the working group concluded that generic AEDs meeting current regulatory criteria for bioequivalence represent a valuable choice in the management of epilepsy by allowing a substantial reduction of treatment costs, particularly in patients initiating monotherapy or adjunctive treatment and in those with persistent seizures. The working group considered that in patients who achieved seizure freedom a modest change in plasma drug levels, which may occasionally occur even after substitution of products that meet bioequivalence criteria, could in rare cases lead to seizure breakthrough. Therefore, generic substitution is not recommended in patients who achieved seizure remission. Switches between a particular generic and another generic should also be preferably avoided. Finally, sustained-release AED formulations should not be used interchangeably with immediate-release brand or generic products. Patients need to be informed about the stringent criteria that currently govern the approval of generic products and about the implications of the use of generic AEDs, and their opinion should be taken into consideration at the time of prescribing.
Perucca
Emilio
E
Clinical Pharmacology Unit and Institute of Neurology IRCCS C. Mondino Foundation, University of Pavia, Pavia, Italy. perucca@unipv.it
Albani
Fiorenzo
F
Capovilla
Giuseppe
G
Bernardina
Bernardo Dalla
BD
Michelucci
Roberto
R
Zaccara
Gaetano
G
D026683:Advisory Committees / Q000592:standards; D000927:Anticonvulsants / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D017277:Drug Approval; D016527:Drug Costs; D011307:Drug Prescriptions / Q000592:standards; D016568:Drugs, Generic / Q000009:adverse effects / Q000191:economics / Q000627:therapeutic use*; D004827:Epilepsy / Q000188:drug therapy*; D006801:Humans; D007390:International Agencies / Q000592:standards; D007558:Italy; D017410:Practice Guidelines as Topic; D013810:Therapeutic Equivalency
D000927:Anticonvulsants; D016568:Drugs, Generic