Epilepsy-Center Berlin-Brandenburg, Department of Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.
Epilepsia. 2018 Jul;59(7):1273-1281. doi: 10.1111/epi.14439. Epub 2018 Jun 12.
Generic antiepileptic drugs (AED) are significantly cheaper than brand name drugs, and may reduce overall health care expenditures. Regulatory bodies in Europe and North America require bioequivalence between generic and innovator drugs with regard to area under the plasma concentration-time curve (AUC) and peak plasma concentration (C ); strict cutoff values have been defined. The main issue is if bioequivalence ensures therapeutic equivalence. Are switches from brand to generic, or between generic AEDs entirely safe or potentially harmful in patients with epilepsy? We summarized and evaluated the available evidence from bioequivalence, health care utilization, and clinical studies on safety of generic AEDs. In most cases, variations in AUC and C were negligible when comparing innovator and generic AEDs. Due to interindividual pharmacokinetic and pharmacodynamic variability, measured differences between innovator and generic drugs may be the same as differences between different lots of the same brand. Studies from several countries based on insurance data have reported an increase in health care usage after switch from brand to generic AEDs; switchback rates are significantly higher for AEDs compared to other compounds. Patients may be confused, and nonadherence may increase, when AEDs are switched between manufacturers, perhaps due to changes in medication shape and color. But clinical studies do not report changes in seizure frequency and tolerability attributable to generics. Sufficient evidence indicates that most generics are bioequivalent to innovator AEDs; they do not pose a relevant risk for patients with epilepsy. However, some patients are reluctant towards variations in color and shape of their AEDs which may result in nonadherence. We recommend administering generics when a new AED is initiated. Switches from brand to generic AEDs for cost reduction and between generics, which is rarely required, generally seem to be safe, but should be accompanied by thorough counseling of patients on low risks.
通用型抗癫痫药物（AED）比品牌药显著便宜，可能降低整体医疗保健支出。欧洲和北美的监管机构要求通用药物与创新药物在血浆浓度-时间曲线下面积（AUC）和血浆峰浓度（C）方面具有生物等效性；已经定义了严格的截止值。主要问题是生物等效性是否能确保治疗等效性。癫痫患者从品牌药换用通用药，或者在通用 AED 之间转换是否完全安全或潜在有害？我们总结和评估了生物等效性、医疗保健利用以及通用 AED 安全性的临床研究方面的现有证据。在大多数情况下，比较创新药物和通用 AED 时，AUC 和 C 的变化可以忽略不计。由于个体间药代动力学和药效动力学的变异性，创新药物和通用药物之间的测量差异可能与同一品牌不同批次之间的差异相同。基于保险数据的来自多个国家的研究报告称，从品牌 AED 换用通用 AED 后医疗保健使用率增加；与其他化合物相比，AED 的换用回原药率显著更高。当 AED 从一个制造商转换到另一个制造商时，患者可能会感到困惑，并且不遵医嘱的可能性会增加，这可能是由于药物形状和颜色的变化。但临床研究并未报告由于使用通用药物而导致癫痫发作频率和耐受性发生变化。有充分证据表明，大多数通用药物与创新型 AED 具有生物等效性；它们不会给癫痫患者带来相关风险。然而，一些患者不喜欢其 AED 药物颜色和形状的变化，这可能导致不遵医嘱。我们建议在开始使用新的 AED 时使用通用药物。出于降低成本而从品牌药换用通用药，以及很少需要的通用药之间的转换，一般来说似乎是安全的，但应在患者中彻底开展低风险的教育。
