Hernández García Ernestina, Lambert Lamazares Brenda, Gómez-Lira Gisela, Mendoza-Torreblanca Julieta Griselda, Duke Lomeli Pamela, López Flores Yessica, Rangel Escobar Laura Elena, Mejía Aranguré Eréndira, Ruiz-Velasco Acosta Silvia, Naranjo Albarrán Lizbeth
Laboratorio de Farmacología, Subdirección de Medicina Experimental, Instituto Nacional de Pediatría, Ciudad de México 04530, Mexico.
Programa de Maestría y Doctorado en Ciencias Matemáticas y de la Especialización en Estadística Aplicada, Instituto de Investigaciones en Matemáticas Aplicadas y en Sistemas, Universidad Nacional Autónoma de México, Ciudad de México 04510, Mexico.
Pharmaceuticals (Basel). 2025 Jul 26;18(8):1116. doi: 10.3390/ph18081116.
Epilepsy is a chronic neurological disease with a relatively high incidence in the pediatric population. Anti-seizure medication (ASM) may cause adverse drug reactions (ADRs), which may occur repeatedly. This study aimed to analyze the recurrence of ADRs caused by ASMs over a period of 122 months in hospitalized Mexican pediatric epilepsy patients. The patients were under monotherapy or polytherapy treatment, with valproic acid (VPA), phenytoin (PHT), and levetiracetam (LEV), among others. A total of 313 patients met the inclusion criteria: 211 experienced ADRs, whereas 102 did not. Patient sex, age, seizure type, nutritional status and related drugs were considered explanatory variables. Four statistical models were used to analyze recurrent events that were defined as "one or more ADRs occurred on a single day", considering both the classification of ADR seriousness and the ASM causing the ADR. A total of 499 recurrence events were identified. The recurrence risk was significantly greater among younger patients for both nonsevere and severe ADRs and among those with focal seizures for nonsevere ADRs. Interestingly, malnutrition was negatively associated with the risk of nonsevere ADRs, and obesity was positively associated with the risk of severe ADRs. Finally, LEV was associated with a significantly greater risk of causing nonsevere ADRs than VPA. However, LEV significantly reduced the risk of severe ADRs compared with VPA, and PHT increased the risk in comparison with VPA. In conclusion, this study offers a robust clinical tool to predict risk factors for the presence and recurrence of ASM-ADRs in pediatric patients with epilepsy.
癫痫是一种慢性神经疾病，在儿科人群中发病率相对较高。抗癫痫药物（ASM）可能会引起药物不良反应（ADR），且这些反应可能会反复出现。本研究旨在分析墨西哥住院儿科癫痫患者在122个月期间由ASM引起的ADR的复发情况。患者接受单药治疗或联合治疗，使用的药物包括丙戊酸（VPA）、苯妥英（PHT）和左乙拉西坦（LEV）等。共有313名患者符合纳入标准：211名经历了ADR，而102名未经历。患者的性别、年龄、癫痫类型、营养状况和相关药物被视为解释变量。使用四种统计模型来分析复发事件，复发事件被定义为“同一天发生一次或多次ADR”，同时考虑ADR严重程度的分类以及引起ADR的ASM。共识别出499次复发事件。对于非严重和严重ADR，年轻患者的复发风险显著更高；对于非严重ADR，局灶性癫痫患者的复发风险也显著更高。有趣的是，营养不良与非严重ADR的风险呈负相关，而肥胖与严重ADR的风险呈正相关。最后，与VPA相比，LEV引起非严重ADR的风险显著更高。然而与VPA相比，LEV显著降低了严重ADR的风险，而PHT与VPA相比增加了风险。总之，本研究提供了一个强大的临床工具，用于预测癫痫儿科患者中ASM-ADR存在和复发的风险因素。
