Generic substitution of levetiracetam resulting in increased incidence of breakthrough seizures.
Generic substitution of levetiracetam resulting in increased incidence of breakthrough seizures.
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DOI：
10.1345/aph.1p765
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发表时间：
2011-05-01
期刊：
影响因子：
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通讯作者：
Jacobson, Mercedes P
中科院分区：
文献类型：
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作者：
Fitzgerald, Christine L;Jacobson, Mercedes P
目的：我们报告4例癫痫发作的发病率增加时，治疗从品牌名称左乙拉西坦（凯普拉），以通用的左乙拉西坦formulations.CASE SUMMARY：患者报告癫痫发作活动增加后，他们的神经科医生治疗从凯普拉通用左乙拉西坦配方。为了确认使用仿制药后癫痫发作活动增加的时间轴，并将这些不良事件报告给MedWatch，我们致电每位患者的药房，收集有关分发日期和仿制药生产商的信息。在左乙拉西坦仿制药导致癫痫发作频率增加后，所有4例患者的治疗均转回凯普拉。癫痫发作的频率在所有患者返回到基线时Keppra reinstituted.Discussion：美国食品和药物管理局（FDA）认为仿制药是治疗等效于其相应的品牌配方时，通用符合生物等效性标准。考虑到左乙拉西坦的线性药代动力学特征，如果患者保持一致的剂量，则癫痫发作控制丧失或血清浓度波动是非预期的。然而，越来越多的证据支持品牌抗癫痫药物（AED）在临床上不等同于仿制药的概念。由于FDA依赖于医疗保健专业人员和消费者向其MedWatch计划自愿报告的不良事件，因此报告不足使得难以量化品牌与仿制药转换的重要性，以及同样重要的仿制药与仿制药转换。结论：在一项大型随机盲法对照研究中对仿制AED的使用进行评估之前，临床医生必须警惕地努力向MedWatch报告由于从AED品牌转换为AED的通用配方而导致的不良事件。
OBJECTIVE: We report on 4 patients having an increased incidence of seizures when treatment was switched from brand name levetiracetam (Keppra) to generic levetiracetam formulations.CASE SUMMARY: Patients reported an increase in seizure activity to their neurologists after treatment was switched from Keppra to generic levetiracetam formulations. To confirm the timeline of increased seizure activity with use of the generic drug and report these adverse events to MedWatch, we made a telephone call to each patient's pharmacy to collect information on dispensing dates and the generic formulations' manufacturers. Subsequent to the increase in seizure frequency with generic levetiracetam, treatment in all 4 patients was switched back to Keppra. Seizure frequency in all patients returned to baseline when Keppra was reinstituted.DISCUSSION: The Food and Drug Administration (FDA) considers generic medications to be therapeutically equivalent to their corresponding brand name formulation when the generic meets bioequivalence criteria. Considering the linear pharmacokinetic profile of levetiracetam, loss of seizure control or fluctuations of serum concentrations are unexpected if the patient remains on a consistent dose. However, there is growing evidence to support the concept that brand name antiepileptic drugs (AEDs) are not clinically equivalent to their generic counterparts. Because the FDA relies on voluntary reporting of adverse events from health-care professionals and consumers to their MedWatch program, underreporting makes it difficult to quantify the significance of brand to generic switches, and, equally important, generic to generic switches.CONCLUSIONS: Until the use of generic AEDs can be evaluated in a large randomized blinded controlled study, clinicians must be vigilant in their efforts to report to MedWatch adverse events resulting from the switch from an AED brand to generic formulation of an AED.