Perucca Emilio, Albani Fiorenzo, Capovilla Giuseppe, Bernardina Bernardo Dalla, Michelucci Roberto, Zaccara Gaetano
Clinical Pharmacology Unit and Institute of Neurology IRCCS C. Mondino Foundation, University of Pavia, Pavia, Italy.
Epilepsia. 2006;47 Suppl 5:16-20. doi: 10.1111/j.1528-1167.2006.00871.x.
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.
近年来，抗癫痫药物（AEDs）仿制药的可获得性一直在增加。鉴于该问题的重要性，意大利癫痫防治联盟（LICE）成立了一个特别工作组，其任务是评估有关仿制药治疗癫痫的有效性和安全性的现有证据，并就其使用提出建议。对文献的仔细回顾发现，没有足够有力的随机对照试验来评估仿制药替代的风险/效益比。尽管有报道称，从品牌产品转换为仿制药后，癫痫发作控制出现丧失或恶化，或出现不良事件，但对证据的批判性评估通常不允许我们确定转换与临床状况变化之间的因果关系。总体而言，工作组得出结论，符合当前生物等效性监管标准的仿制药AEDs是癫痫管理中的一个有价值的选择，因为它可以大幅降低治疗成本，特别是在开始单药治疗或辅助治疗的患者以及癫痫持续发作的患者中。工作组认为，在癫痫发作得到控制的患者中，即使在替换符合生物等效性标准的产品后偶尔可能出现的血浆药物水平的适度变化，在极少数情况下也可能导致癫痫发作突破。因此，不建议在癫痫发作缓解的患者中进行仿制药替代。也应尽量避免在特定仿制药与另一种仿制药之间进行转换。最后，缓释AED制剂不应与速释品牌或仿制药产品互换使用。需要告知患者目前管理仿制药批准的严格标准以及使用仿制药AEDs的影响，并且在开处方时应考虑他们的意见。
