The National Center for Epilepsy, Sandvika, and Department of Pharmacology, Oslo University Hospital, Oslo, Norway.
Curr Neuropharmacol. 2010 Sep;8(3):254-67. doi: 10.2174/157015910792246254.
Antiepileptic drugs (AEDs) are widely used as long-term adjunctive therapy or as monotherapy in epilepsy and other indications and consist of a group of drugs that are highly susceptible to drug interactions. The purpose of the present review is to focus upon clinically relevant interactions where AEDs are involved and especially on pharmacokinetic interactions. The older AEDs are susceptible to cause induction (carbamazepine, phenobarbital, phenytoin, primidone) or inhibition (valproic acid), resulting in a decrease or increase, respectively, in the serum concentration of other AEDs, as well as other drug classes (anticoagulants, oral contraceptives, antidepressants, antipsychotics, antimicrobal drugs, antineoplastic drugs, and immunosupressants). Conversely, the serum concentrations of AEDs may be increased by enzyme inhibitors among antidepressants and antipsychotics, antimicrobal drugs (as macrolides or isoniazid) and decreased by other mechanisms as induction, reduced absorption or excretion (as oral contraceptives, cimetidine, probenicid and antacides). Pharmacokinetic interactions involving newer AEDs include the enzyme inhibitors felbamate, rufinamide, and stiripentol and the inducers oxcarbazepine and topiramate. Lamotrigine is affected by these drugs, older AEDs and other drug classes as oral contraceptives. Individual AED interactions may be divided into three levels depending on the clinical consequences of alterations in serum concentrations. This approach may point to interactions of specific importance, although it should be implemented with caution, as it is not meant to oversimplify fact matters. Level 1 involves serious clinical consequences, and the combination should be avoided. Level 2 usually implies cautiousness and possible dosage adjustments, as the combination may not be possible to avoid. Level 3 refers to interactions where dosage adjustments are usually not necessary. Updated knowledge regarding drug interactions is important to predict the potential for harmful or lacking effects involving AEDs.
抗癫痫药物（AEDs）广泛用于癫痫和其他适应证的长期辅助治疗或单药治疗，包括一组易发生药物相互作用的药物。本综述的目的是重点关注涉及 AED 的临床相关相互作用，特别是药代动力学相互作用。较老的 AED 易引起诱导（卡马西平、苯巴比妥、苯妥英、扑米酮）或抑制（丙戊酸），分别导致其他 AED 以及其他药物类别的血清浓度降低或升高（抗凝剂、口服避孕药、抗抑郁药、抗精神病药、抗菌药物、抗肿瘤药物和免疫抑制剂）。相反，抗抑郁药和抗精神病药中的酶抑制剂、抗菌药物（如大环内酯类或异烟肼）可能会增加 AED 的血清浓度，而其他机制如诱导、吸收或排泄减少（如口服避孕药、西咪替丁、丙磺舒和抗酸剂）可能会降低 AED 的血清浓度。涉及新型 AED 的药代动力学相互作用包括酶抑制剂非氨酯、鲁非酰胺和 stiripentol 以及诱导剂奥卡西平和托吡酯。拉莫三嗪受这些药物、较老的 AED 和其他药物类别的影响，如口服避孕药。根据血清浓度改变的临床后果，个体 AED 相互作用可分为三个级别。这种方法可能指向特定的重要相互作用，尽管应该谨慎实施，因为它并不是要简化事实。第 1 级涉及严重的临床后果，应避免联合使用。第 2 级通常意味着谨慎和可能的剂量调整，因为可能无法避免联合使用。第 3 级是指通常不需要调整剂量的相互作用。更新的药物相互作用知识对于预测涉及 AED 的有害或缺乏效果的潜在风险非常重要。
