University of California, San Francisco, Department of Clinical Pharmacy, 490 Illinois Street Floor 3, San Francisco 94158, CA, United States.
University of California, San Francisco, School of Medicine, 550 16th Street, San Francisco 95158, CA, United States.
Epilepsy Res. 2022 Aug;184:106947. doi: 10.1016/j.eplepsyres.2022.106947. Epub 2022 May 23.
There have been several reports that switching formulations of antiseizure medications (ASMs) has been associated with a deterioration of seizure control, seizure relapse or increased adverse effects. Considering recent findings that excipients, namely purported inactive ingredients, may nevertheless exert biological effects, it is possible that the variation in adverse event profile of antiseizure drugs may be related to differences in excipients. To test our hypothesis, we constructed a new research tool to connect FDA-compiled adverse event reports to the excipient in the medicine. Analysis of adverse events to formulations of five different second-generation antiseizure drugs - gabapentin, lamotrigine, levetiracetam, oxcarbazepine, and topiramate - showed several significant associations between specific excipient in the formulations and an adverse event when compared to the same medicine formulated with other excipients. Epilepsy and seizure adverse events were associated with multiple excipients across gabapentin, lamotrigine, and levetiracetam formulations. A different group of excipients were associated with reports of hypersensitivity reactions including urticaria, rash, erythema, and Stevens-Johnson syndrome. Our study provides a novel approach to analyzing post-market surveillance reports by including excipients. It may be useful to clinicians when evaluating select patient groups that may be refractory to pharmacological treatment or experience worsening adverse events when switching formulations of the same antiseizure medicine.
已有多项报告指出，抗癫痫药物（ASM）的配方更换与癫痫控制恶化、癫痫复发或不良反应增加有关。考虑到最近发现赋形剂（即所谓的非活性成分）可能具有生物学效应，抗癫痫药物不良反应谱的差异可能与赋形剂的差异有关。为了验证我们的假设，我们构建了一个新的研究工具，将 FDA 编译的不良反应报告与药物中的赋形剂联系起来。对五种不同第二代抗癫痫药物（加巴喷丁、拉莫三嗪、左乙拉西坦、奥卡西平和托吡酯）配方的不良反应进行分析，与使用其他赋形剂配制的相同药物相比，发现配方中特定赋形剂与不良反应之间存在几个显著关联。癫痫和癫痫发作不良反应与加巴喷丁、拉莫三嗪和左乙拉西坦配方中的多种赋形剂有关。一组不同的赋形剂与过敏反应报告有关，包括荨麻疹、皮疹、红斑和史蒂文斯-约翰逊综合征。我们的研究通过纳入赋形剂为分析上市后监测报告提供了一种新方法。当评估可能对药物治疗有抗性或在使用相同抗癫痫药物的配方时出现不良反应恶化的特定患者群体时，它可能对临床医生有用。
