Abstract：
BACKGROUND: Our objective was to provide expert consensus recommendations to improve treatment tolerability through dose adjustments of concomitant antiseizure medications (ASMs) during addition of cenobamate to existing ASM therapy in adult patients with uncontrolled focal seizures.
METHODS: A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided.
RESULTS: We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy.
CONCLUSIONS: The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.
Some people with epilepsy need to take more than one seizure medicine as part of their treatment. Taking more than one seizure medicine, however, can increase the risk of unwanted side effects. One approach to preventing side effects when adding a new seizure medicine is to lower the amount (dose) of existing seizure medicines. Cenobamate is a newer seizure medicine available in the USA for adults with focal seizures (also referred to as partial-onset seizures). Cenobamate, like many seizure medicines, must be titrated over time to a target dose. A group of epilepsy specialists met and developed recommendations for when and how to change the doses of existing seizure medicines when adding cenobamate. The goal of these recommendations is to prevent or reduce side effects like sleepiness or dizziness. The authors recommend that the dose of specific seizure medicines, including clobazam, lacosamide, phenytoin, and phenobarbital, be lowered as cenobamate is started or as cenobamate’s dose is being increased (but before side effects occur). Regular doses of other seizure medicines can be lowered if a side effect occurs because reducing the dose of the other seizure medications can often stop the side effect. These recommendations may help patients successfully reach their optimal dose of cenobamate with fewer side effects, potentially improving their seizure control. Video Abstract: Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.
METHODS: A panel of seven epileptologists experienced in the use of ASMs, including cenobamate, used a modified Delphi process to reach consensus. The panelists discussed tolerability issues with concomitant ASMs during cenobamate titration and practical strategies for dose adjustments that may prevent or mitigate adverse effects. The resulting recommendations consider concomitant ASM dose level and specify proactive (prior to report of an adverse effect) and reactive (in response to report of an adverse effect) dose adjustment suggestions based on concomitant ASM pharmacokinetic and pharmacodynamic interactions with cenobamate. Specific dose adjustment recommendations are provided.
RESULTS: We recommend proactively lowering the dose of clobazam, phenytoin, and phenobarbital due to their known drug-drug interactions with cenobamate, and lacosamide due to a pharmacodynamic interaction with cenobamate, to prevent adverse effects during cenobamate titration. Reactive lowering of a concomitant ASM dose is sufficient for other ASMs at standard dosing owing to quick resolution of adverse effects. For carbamazepine and lamotrigine doses exceeding the upper end of standard dosing (e.g., carbamazepine, greater than 1200 mg/day; lamotrigine, greater than 500 mg/day), we encourage consideration of proactive dose reduction at cenobamate 200 mg/day to prevent potential adverse effects. All dose reductions for adverse effects can be repeated every 2 weeks as dictated by the adverse effects. At cenobamate 200 mg/day, we recommend that patients be evaluated for marked improvement of seizures and further dose reductions be considered to reduce potentially unnecessary polypharmacy.
CONCLUSIONS: The primary goal of the recommended dose reductions of concomitant ASMs is to prevent or resolve adverse effects, thereby allowing cenobamate to reach the optimal dose to achieve the maximal potential of improving seizure control.
Some people with epilepsy need to take more than one seizure medicine as part of their treatment. Taking more than one seizure medicine, however, can increase the risk of unwanted side effects. One approach to preventing side effects when adding a new seizure medicine is to lower the amount (dose) of existing seizure medicines. Cenobamate is a newer seizure medicine available in the USA for adults with focal seizures (also referred to as partial-onset seizures). Cenobamate, like many seizure medicines, must be titrated over time to a target dose. A group of epilepsy specialists met and developed recommendations for when and how to change the doses of existing seizure medicines when adding cenobamate. The goal of these recommendations is to prevent or reduce side effects like sleepiness or dizziness. The authors recommend that the dose of specific seizure medicines, including clobazam, lacosamide, phenytoin, and phenobarbital, be lowered as cenobamate is started or as cenobamate’s dose is being increased (but before side effects occur). Regular doses of other seizure medicines can be lowered if a side effect occurs because reducing the dose of the other seizure medications can often stop the side effect. These recommendations may help patients successfully reach their optimal dose of cenobamate with fewer side effects, potentially improving their seizure control. Video Abstract: Dose Adjustment of Concomitant Antiseizure Medications During Cenobamate Treatment: Expert Opinion Consensus Recommendations.
摘要：
背景：我们的目标是提供专家共识建议，以通过在未控制的局灶性癫痫发作的成年患者的现有ASM治疗中添加西伯那酯的同时抗癫痫药物（ASM）的剂量调整来提高治疗耐受性。
方法：由7名癫痫专家组成的小组在使用ASM方面经验丰富，包括西诺酸盐,使用修改的Delphi过程达成共识。小组成员讨论了在西诺酸盐滴定期间伴随ASM的耐受性问题，以及可以预防或减轻不良反应的剂量调整的实际策略。由此产生的建议考虑了伴随的ASM剂量水平，并根据伴随的ASM药代动力学和药效学相互作用，指定了主动（在报告不良反应之前）和反应性（响应于报告不良反应）剂量调整建议。提供了具体的剂量调整建议。
结果：我们建议积极降低氯巴赞的剂量，苯妥英,和苯巴比妥由于它们已知的药物-药物相互作用，和拉科沙胺由于药效学相互作用与cenobamate，以防止cenobamate滴定过程中的不利影响。伴随ASM剂量的反应性降低对于其他ASM在标准剂量下是足够的,这是由于副作用的快速解决。对于超过标准剂量上限的卡马西平和拉莫三嗪剂量（例如，卡马西平,大于1200毫克/天；拉莫三嗪，大于500毫克/天)，我们鼓励考虑主动减量西诺膦酸200mg/天,以防止潜在的不良反应.不良反应的所有剂量减少可以根据不良反应的指示每2周重复一次。在西诺巴特200毫克/天，我们建议对患者进行癫痫发作明显改善的评估,并考虑进一步减量以减少潜在的不必要的多重用药.
结论：推荐减少伴随ASM的剂量的主要目标是预防或消除不良反应，从而允许西诺本达到最佳剂量，以实现改善癫痫发作控制的最大潜力。
一些癫痫患者需要服用一种以上的癫痫药物作为治疗的一部分。服用不止一种癫痫药，然而,会增加不必要副作用的风险。在添加新的癫痫发作药物时防止副作用的一种方法是降低现有癫痫发作药物的量(剂量)。Cenobamate是一种在美国可用于局灶性癫痫发作（也称为部分发作性癫痫发作）的成人的较新的癫痫发作药物。Cenobamate,像许多癫痫药物一样，必须随着时间的推移滴定到目标剂量。一组癫痫专家会面并提出了建议，建议在添加cenobamate时何时以及如何更改现有癫痫发作药物的剂量。这些建议的目的是防止或减少嗜睡或头晕等副作用。作者建议特定癫痫药物的剂量，包括Clobazam,拉科沙胺,苯妥英,还有苯巴比妥,当开始时或当西诺酸盐的剂量增加时(但在副作用发生之前)降低。如果发生副作用，可以降低其他癫痫发作药物的常规剂量，因为减少其他癫痫发作药物的剂量通常可以阻止副作用。这些建议可能会帮助患者成功地达到他们的最佳剂量的西伯酸盐的副作用少，有可能改善他们的癫痫控制。
方法：由7名癫痫专家组成的小组在使用ASM方面经验丰富，包括西诺酸盐,使用修改的Delphi过程达成共识。小组成员讨论了在西诺酸盐滴定期间伴随ASM的耐受性问题，以及可以预防或减轻不良反应的剂量调整的实际策略。由此产生的建议考虑了伴随的ASM剂量水平，并根据伴随的ASM药代动力学和药效学相互作用，指定了主动（在报告不良反应之前）和反应性（响应于报告不良反应）剂量调整建议。提供了具体的剂量调整建议。
结果：我们建议积极降低氯巴赞的剂量，苯妥英,和苯巴比妥由于它们已知的药物-药物相互作用，和拉科沙胺由于药效学相互作用与cenobamate，以防止cenobamate滴定过程中的不利影响。伴随ASM剂量的反应性降低对于其他ASM在标准剂量下是足够的,这是由于副作用的快速解决。对于超过标准剂量上限的卡马西平和拉莫三嗪剂量（例如，卡马西平,大于1200毫克/天；拉莫三嗪，大于500毫克/天)，我们鼓励考虑主动减量西诺膦酸200mg/天,以防止潜在的不良反应.不良反应的所有剂量减少可以根据不良反应的指示每2周重复一次。在西诺巴特200毫克/天，我们建议对患者进行癫痫发作明显改善的评估,并考虑进一步减量以减少潜在的不必要的多重用药.
结论：推荐减少伴随ASM的剂量的主要目标是预防或消除不良反应，从而允许西诺本达到最佳剂量，以实现改善癫痫发作控制的最大潜力。
一些癫痫患者需要服用一种以上的癫痫药物作为治疗的一部分。服用不止一种癫痫药，然而,会增加不必要副作用的风险。在添加新的癫痫发作药物时防止副作用的一种方法是降低现有癫痫发作药物的量(剂量)。Cenobamate是一种在美国可用于局灶性癫痫发作（也称为部分发作性癫痫发作）的成人的较新的癫痫发作药物。Cenobamate,像许多癫痫药物一样，必须随着时间的推移滴定到目标剂量。一组癫痫专家会面并提出了建议，建议在添加cenobamate时何时以及如何更改现有癫痫发作药物的剂量。这些建议的目的是防止或减少嗜睡或头晕等副作用。作者建议特定癫痫药物的剂量，包括Clobazam,拉科沙胺,苯妥英,还有苯巴比妥,当开始时或当西诺酸盐的剂量增加时(但在副作用发生之前)降低。如果发生副作用，可以降低其他癫痫发作药物的常规剂量，因为减少其他癫痫发作药物的剂量通常可以阻止副作用。这些建议可能会帮助患者成功地达到他们的最佳剂量的西伯酸盐的副作用少，有可能改善他们的癫痫控制。
