Department of Pharmacy Services, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Pediatr Transplant. 2021 Jun;25(4):e14026. doi: 10.1111/petr.14026. Epub 2021 Apr 24.
Busulfan is a chemotherapy agent used in hematopoietic stem cell transplant (HSCT) conditioning regimens. Busulfan is associated with tonic-clonic seizures in ~10% of patients if administered without seizure prophylaxis. Historically, phenytoin was the most commonly utilized seizure prophylaxis agent; however, phenytoin is associated with CYP450 drug interactions and potentially increases the clearance of busulfan. Levetiracetam is being used more recently for busulfan seizure prophylaxis and is not associated with drug-drug interactions; however, data supporting use in pediatric patients are limited. The primary objective is to determine whether there is any difference in seizure rates or safety profile between phenytoin and levetiracetam when used for seizure prophylaxis.
We conducted a retrospective chart review including patients who received busulfan between 2010 and 2019 were identified. The data were evaluated to compare the incidence of busulfan-induced seizures in HSCT patients receiving either phenytoin or levetiracetam and to determine the impact of drug-drug interactions on treatment outcomes/adverse events.
A total of 342 patients were included with a median age of six years. Overall, five patients within the phenytoin group (n = 126) (4%) and zero patients in the levetiracetam group (n = 216) experienced a seizure (P = .007). There were no differences in liver enzyme elevations, recurrence rates of primary disease, and veno-occlusive disease.
Levetiracetam is effective at preventing seizures associated with busulfan administration with no clinically significant adverse effects when compared to phenytoin.
白消安是一种用于造血干细胞移植（HSCT）预处理方案的化疗药物。如果没有给予癫痫预防，约有 10%的患者在使用白消安时会出现强直阵挛性发作。历史上，苯妥英钠是最常用的癫痫预防药物；然而，苯妥英钠与 CYP450 药物相互作用有关，并可能增加白消安的清除率。左乙拉西坦最近被用于白消安癫痫预防，并且与药物相互作用无关；然而，支持在儿科患者中使用的数据有限。主要目的是确定在用于癫痫预防时，苯妥英钠和左乙拉西坦在癫痫发作率或安全性方面是否存在差异。
我们进行了一项回顾性图表审查，包括 2010 年至 2019 年间接受白消安治疗的患者。评估数据以比较接受苯妥英钠或左乙拉西坦治疗的 HSCT 患者中白消安引起的癫痫发作发生率，并确定药物相互作用对治疗结果/不良事件的影响。
共有 342 例患者纳入研究，中位年龄为 6 岁。总体而言，在苯妥英钠组（n=126）中有 5 例（4%）患者（n=126）和左乙拉西坦组（n=216）中无患者发生癫痫（P=0.007）。肝酶升高、原发性疾病复发率和静脉闭塞性疾病无差异。
与苯妥英钠相比，左乙拉西坦在预防与白消安给药相关的癫痫发作方面有效，且无临床显著不良影响。
