Armijo J A, Sánchez M B, Campos C, Adín J
Departamento de Fisiología y Farmacología, Universidad de Cantabria, España.
Rev Neurol. 2006;42(11):681-90.
Antiepileptic drugs, which often have to be used in patients with cancer, can have important effects on the results offered by antineoplastic agents. Here, we review the influence of antiepileptic drugs on antineoplastic agents and the influence of antineoplastic agents on antiepileptic drugs; measures to prevent such interactions are also suggested.
Antiepileptic drugs that induce cytochrome P450, such as carbamazepine, phenytoin and phenobarbital, can reduce the levels and effects of antineoplastics that metabolise by means of this enzyme, for example, taxanes, Vinca alkaloids, methotrexate, teniposide and camptothecin. Furthermore, enzyme-inducing antiepileptic drugs diminish the levels and effects of many other drugs that can be administered to oncology patients, such as other antiepileptic drugs used in polytherapy, narcotic analgesics, antidepressants, antipsychotics or antibiotics. In contrast, valproate can increase the toxicity of etoposide or nitrosoureas. Moreover, antineoplastic agents like cisplatin or corticoids can lower the effectiveness of phenytoin and methotrexate has a similar effect on valproate. In contrast, 5-fluorouracil can increase the toxicity of phenytoin. Pharmacodynamic interactions are also possible.
Information about the clinical consequences of the interactions between antiepileptics and antineoplastic agents is often based on cases or series of cases, but a growing body of evidence from pharmacokinetic studies shows that enzyme-inducing antiepileptics exert an important influence on the effectiveness of the antineoplastic agents. It is therefore recommendable to avoid them and replace them with non-enzyme-inducing antiepileptics, such as gabapentin, lamotrigine, levetiracetam, pregabalin, topiramate or zonisamide. When enzyme-inducing antiepileptics have to be used, it is likely that higher doses of antineoplastic agents or other inducible drugs will have to be utilised.
抗癫痫药物常需用于癌症患者，其可能对抗肿瘤药物的疗效产生重要影响。在此，我们综述抗癫痫药物对抗肿瘤药物的影响以及抗肿瘤药物对抗癫痫药物的影响；同时也提出预防此类相互作用的措施。
诱导细胞色素P450的抗癫痫药物，如卡马西平、苯妥英和苯巴比妥，可降低通过该酶代谢的抗肿瘤药物的水平和疗效，例如紫杉烷类、长春花生物碱、甲氨蝶呤、替尼泊苷和喜树碱。此外，诱导酶的抗癫痫药物还会降低许多其他可用于肿瘤患者的药物的水平和疗效，如联合治疗中使用的其他抗癫痫药物、麻醉性镇痛药、抗抑郁药、抗精神病药或抗生素。相比之下，丙戊酸盐可增加依托泊苷或亚硝基脲的毒性。此外，顺铂或皮质类固醇等抗肿瘤药物可降低苯妥英的疗效，甲氨蝶呤对丙戊酸盐也有类似作用。相反，5-氟尿嘧啶可增加苯妥英的毒性。药效学相互作用也有可能发生。
关于抗癫痫药物与抗肿瘤药物相互作用的临床后果的信息通常基于病例或病例系列，但越来越多的药代动力学研究证据表明，诱导酶的抗癫痫药物对抗肿瘤药物的疗效有重要影响。因此，建议避免使用它们，并用非诱导酶的抗癫痫药物替代，如加巴喷丁、拉莫三嗪、左乙拉西坦、普瑞巴林、托吡酯或唑尼沙胺。当必须使用诱导酶的抗癫痫药物时，可能需要使用更高剂量的抗肿瘤药物或其他可诱导药物。
