Pellock J M
Division of Child Neurology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298, USA.
Drug Saf. 1999 Sep;21(3):225-39. doi: 10.2165/00002018-199921030-00006.
Felbamate demonstrates a unique therapeutic profile and often results in seizure control when other agents fail. Its use has been associated with risks for aplastic anaemia and hepatic failure. A number of confounding factors makes the actual incidence rate for each adverse effect difficult to determine. However, certain risk factors are common in reported cases. In order to minimise the risk, at the present time, it is necessary to rely on the clinical profile of the patients reporting these adverse effects. The patient reporting aplastic anaemia is usually female, Caucasian, and an adult. The dose did not appear to be a factor and the time to onset of aplastic anaemia was less than 1 year for all patients. Concomitant medications and diseases may play an important role. Patients with reported aplastic anaemia generally had a history of a serious allergy or toxicity to other anticonvulsants and/or a background of having had a cytopenia due to other anticonvulsants, and a diagnosis or serological evidence of concomitant immune disorder. The demographics associated with hepatic failure are less well defined. Patients were also predominantly female, were equally divided among adult and paediatric patients, and had a broad range of time to presentation of hepatotoxicity following felbamate therapy. Concomitant medications again play an important role with, in this case, valproic acid (sodium valproate), phenytoin and carbamazepine being the most frequent. In 50% of the population, hepatic failure was not felt to be due to felbamate but associated with confounding factors including status epilepticus, paracetamol (acetaminophen) toxicity, hepatitis and shock liver. Initial research has failed to provide a diagnostic indicator. However, work on a potential intermediate felbamate metabolite has suggested the formation of a reactive aldehyde whose end products have been detected in the urine of felbamate treated patients. Until these data are confirmed, the medical history, clinical picture, and laboratory testing, should be used to identify patients at risk. The risks for toxicity with felbamate should be evaluated before starting treatment. In addition, liver function tests and complete blood count (CBC) prior to therapy and at clinically rational intervals should be conducted. Patients must be educated in the likely prodromal symptoms of potential marrow/liver toxicity. Felbamate is too valuable an anticonvulsant to be relegated to the therapeutic scrap heap. With monitoring, patient education, and continued research to further elucidate risk factors, felbamate can be a viable therapeutic agent for patients with epilepsy.
非氨酯具有独特的治疗特点，当其他药物治疗无效时，它常常能控制癫痫发作。其使用与再生障碍性贫血和肝衰竭风险相关。一些混杂因素使得每种不良反应的实际发生率难以确定。然而，某些风险因素在报告的病例中很常见。为了将风险降至最低，目前有必要依据报告这些不良反应的患者的临床特征。报告再生障碍性贫血的患者通常为成年女性、白种人。剂量似乎不是一个因素，所有患者再生障碍性贫血的发病时间均少于1年。同时使用的药物和疾病可能起重要作用。报告有再生障碍性贫血的患者通常有对其他抗惊厥药严重过敏或中毒的病史，和/或因其他抗惊厥药导致血细胞减少的病史，以及有免疫紊乱的诊断或血清学证据。与肝衰竭相关的人口统计学特征不太明确。患者也以女性为主，成年患者和儿童患者各占一半，非氨酯治疗后出现肝毒性的时间范围很广。同时使用的药物同样起重要作用，在这种情况下，丙戊酸（丙戊酸钠）、苯妥英和卡马西平最为常见。在50%的患者中，肝衰竭被认为并非由非氨酯引起，而是与包括癫痫持续状态、对乙酰氨基酚（扑热息痛）中毒、肝炎和休克肝等混杂因素有关。初步研究未能提供诊断指标。然而，对非氨酯一种潜在中间代谢产物的研究表明会形成一种反应性醛，其终产物已在接受非氨酯治疗患者的尿液中检测到。在这些数据得到证实之前，应利用病史、临床表现和实验室检查来识别有风险的患者。在开始治疗前应评估非氨酯的毒性风险。此外，在治疗前以及按临床合理间隔进行肝功能检查和全血细胞计数（CBC）。必须让患者了解潜在骨髓/肝毒性可能出现的前驱症状。非氨酯作为一种抗惊厥药非常有价值，不应被弃用。通过监测、患者教育以及持续研究以进一步阐明风险因素，非氨酯可以成为癫痫患者一种可行的治疗药物。
