Generic substitution in the treatment of epilepsy - Case evidence of breakthrough seizures
Generic substitution in the treatment of epilepsy - Case evidence of breakthrough seizures
复制标题
DOI：
10.1212/01.wnl.0000319958.37502.8e
复制
发表时间：
2008-08-12
期刊：
影响因子：
9.9
通讯作者：
Haskins, L. S.
中科院分区：
文献类型：
--
作者：
Berg, M. J.;Gross, R. A.;Haskins, L. S.
目的：有人担心仿制药和品牌抗癫痫药 (AED) 的治疗效果可能不同。本研究调查了非专利 AED 替代可能如何产生负面后果。方法：参与非专利 AED 替代大型调查的 150 名医生中有 69 名填写了病例审查表，该表格涉及一名因非专利 AED 导致癫痫发作失控的患者。 19 名患者被排除在分析之外。 结果：50 名患者在使用品牌 AED 后控制良好，随后在改用仿制药且没有其他诱发因素的情况下出现了突破性癫痫发作或癫痫发作频率增加。 AED 包括苯妥英（15 例）、丙戊酸（14 例）、卡马西平（7 例）、加巴喷丁（8 例）和唑尼沙胺（8 例）。两名患者同时服用两种 AED，但后来都改为仿制药。在 26 例患者中，在仿制药替代前后血清 AED 水平均已知。 21 人在服用非专利药物后出现突破性癫痫发作时，其水平较低。癫痫发作失控对生活质量产生负面影响，包括失去驾驶权 (n = 30) 和缺课/工作日 (n = 9)。结论：从品牌抗癫痫药 (AED) 改为仿制药可能会导致癫痫发作。这引发了人们的担忧，即当前的食品和药物治疗等效性测试法规可能不足以用于 AED，并表明需要更多的临床证据。医生、药剂师、患者和政策制定者应该意识到，对于某些患者来说，从品牌 AED 转向仿制药 AED 可能存在风险。
Objective: There are concerns that generic and brand antiepileptic drugs (AEDs) may not be therapeutically equivalent. This study investigated how generic AED substitution may have negative consequences.Methods: Sixty-nine of 150 physicians who participated in a large survey on generic AED substitution completed a case review form regarding a patient who experienced a loss of seizure control due to a generic AED. Nineteen were excluded from analysis.Results: Fifty patients, well-controlled on a brand AED, subsequently experienced a breakthrough seizure or increased seizure frequency after switching to a generic without other provoking factors. AEDs included phenytoin (15 cases), valproic acid (14), carbamazepine (7), gabapentin (8), and zonisamide (8). Two patients were on a combination of two AEDs, both of which were switched to generics. In 26 cases serum AED levels were known both before and after generic substitution. Twenty-one had lower levels at the time of the breakthrough seizure on the generic medication. Loss of seizure control had a negative impact on quality of life, including loss of driving privileges (n = 30) and missed school/work days (n = 9).Conclusions: Changing from a brand antiepileptic drug (AED) to a generic may result in seizures. This raises the concern that current Food and Drug therapeutic equivalence testing regulations may not be adequate for AEDs and suggests that more clinical evidence is needed. Physicians, pharmacists, patients, and policy makers should be aware that for some patients there may be risks associated with switching from brand to generic AEDs.