Abstract:
The goal of epilepsy treatment is seizure freedom, typically with antiseizure medication (ASM). If patients fail to attain seizure control despite two trials of appropriately chosen ASMs at adequate doses, they are classified as having drug-resistant epilepsy (DRE). Adverse events (AEs) commonly occur in people with DRE because they are typically on ⩾2 ASMs, increasing the potential for drug-drug interactions. Early emerging AEs may impact adherence, decrease quality of life, and delay achieving optimal treatment dosages. Cenobamate is an oral ASM with a long half-life which has proven to be highly effective in clinical trials. An international Delphi panel of expert epileptologists experienced in the clinical use of cenobamate and other ASMs was convened to develop consensus best practices for managing patients during and after cenobamate titration, with consideration for its known pharmacokinetic and pharmacodynamic interactions, to allow patients to reach the most appropriate cenobamate dose while limiting tolerability issues. The modified Delphi process included one open-ended questionnaire and one virtual face-to-face meeting. Participants agreed that cenobamate can be prescribed for most patients experiencing focal-onset seizures. Patients initiating cenobamate therapy should have access to healthcare professionals as needed and their treatment response should be evaluated at the 100-mg dose. Patients with intellectual disabilities may need additional support to navigate the titration period. Proactive down-titration or withdrawal of sodium channel blockers (SCBs) is recommended when concomitant ASM regimens include ⩾2 SCBs. When applicable, maintaining a concomitant clobazam dose at ~5-10 mg may be beneficial. Patients taking oral contraceptives, newer oral anticoagulants, or HIV antiretroviral medications should be monitored for potential interactions. Because clinical evidence informing treatment decisions is limited, guidance regarding dose adjustments of non-ASM drugs was not developed beyond specific recommendations presented in the Summary of Product Characteristics.
摘要:
癫痫治疗的目标是癫痫发作的自由,通常与抗癫痫药物(ASM)。如果患者尽管在适当的剂量下进行了两次适当选择的ASM试验,但仍未能控制癫痫发作,他们被归类为耐药癫痫(DRE)。不良事件(AE)通常发生在DRE患者中,因为他们通常在2ASM上,增加药物-药物相互作用的可能性。早期出现的AE可能会影响依从性,降低生活质量,并延迟达到最佳治疗剂量。Cenobamate是一种具有长半衰期的口服ASM,已被证明在临床试验中非常有效。召集了一个国际德尔菲专家小组,该小组由在西诺本和其他ASM的临床使用方面经验丰富的癫痫专家组成,以制定在西诺本滴定期间和之后管理患者的共识最佳实践。考虑到其已知的药代动力学和药效学相互作用,以允许患者达到最合适的锡溴酸盐剂量,同时限制耐受性问题。修改后的Delphi流程包括一份开放式问卷和一次虚拟面对面会议。参与者一致认为,对于大多数发生局灶性发作性癫痫发作的患者,可以开西伯甲酯。开始西诺本治疗的患者应根据需要与医疗保健专业人员接触,并应在100mg剂量下评估其治疗反应。智障患者可能需要额外的支持来浏览滴定期。当伴随的ASM方案包括2SCB时,建议主动下调或撤回钠通道阻滞剂(SCB)。如果适用,将伴随的氯巴赞剂量维持在〜5-10mg可能是有益的。服用口服避孕药的患者,新型口服抗凝剂,或HIV抗逆转录病毒药物应监测潜在的相互作用。因为告知治疗决定的临床证据有限,关于非ASM药物剂量调整的指导并未超出产品特性摘要中的具体建议.