Wellington K, Goa K L
Adis International Limited, Mairangi Bay, Auckland, New Zealand.
CNS Drugs. 2001;15(2):137-63. doi: 10.2165/00023210-200115020-00005.
Oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) is a 10-keto analogue of carbamazepine with anticonvulsant activity. In newly diagnosed adult patients, oxcarbazepine monotherapy is as effective as phenytoin and vaiproic acid at reducing generalised tonic-clonic and partial seizure frequency. Furthermore, oxcarbazepine 2400 mg/day as monotherapy has also proved effective in the treatment of refractory partial seizures in adult patients. Oxcarbazepine 600, 1200 and 2400 mg/day as adjunctive therapy significantly reduced seizure frequency compared with placebo in 692 patients with refractory partial seizures. The efficacy of oxcarbazepine monotherapy is similar to that of phenytoin in the treatment of children and adolescents with newly diagnosed partial or generalised tonic-clonic seizures. Additionally, adjunctive therapy with oxcarbazepine was significantly more effective than placebo at reducing seizure frequency in children and adolescents with refractory partial seizures. The most commonly reported adverse events associated with oxcarbazepine monotherapy and/or adjunctive therapy in adults and/or children are somnolence, dizziness, headache, nausea and vomiting. Oxcarbazepine monotherapy is better tolerated than phenytoin (in both adults and children) and valproic acid (in adults), and although 75 to 90% of adult patients in 5 recent monotherapy studies reported adverse events while receiving oxcarbazepine, <8% withdrew from treatment because of them. Acute hyponatraemia, although usually asymptomatic, develops in 2.7% of patients treated with oxcarbazepine. Adverse events most likely to resolve upon switching to oxcarbazepine therapy from treatment with carbamazepine are undetermined skin reactions (rashes, pruritus, eczema), allergic reactions and a combination of malaise, dizziness and headache. Although oxcarbazepine does have a clinically significant interaction with some drugs (e.g. phenytoin and oral contraceptives), it has a lower propensity for interactions than older antiepileptic drugs (AEDs) because its major metabolic pathway is mediated by noninducible enzymes.
Oxcarbazepine as monotherapy is a viable alternative to established AEDs in the treatment of partial and generalised tonic-clonic seizures in adults and children. Furthermore, it is also effective as adjunctive therapy in the treatment of refractory partial seizures in both age groups. In addition, the drug is tolerated better than the older, established AEDs, and has a lower potential for drug interactions. These attributes make oxcarbazepine an effective component in the initial treatment of newly diagnosed partial and generalised tonic-clonic seizures, and also as an adjunct for medically intractable partial seizures in both adults and children.
奥卡西平(10,11 - 二氢 - 10 - 氧代 - 5H - 二苯并[b,f]氮杂䓬 - 5 - 甲酰胺)是卡马西平的10 - 酮类似物,具有抗惊厥活性。在新诊断的成年患者中,奥卡西平单药治疗在降低全身强直 - 阵挛发作和部分性发作频率方面与苯妥英钠和丙戊酸效果相当。此外,奥卡西平2400毫克/天单药治疗已被证明对成年患者难治性部分性发作有效。在692例难治性部分性发作患者中,与安慰剂相比,奥卡西平600、1200和2400毫克/天作为辅助治疗可显著降低发作频率。奥卡西平单药治疗在治疗新诊断的部分性或全身强直 - 阵挛发作的儿童和青少年中疗效与苯妥英钠相似。此外,在难治性部分性发作的儿童和青少年中,奥卡西平辅助治疗在降低发作频率方面比安慰剂显著更有效。与奥卡西平单药治疗和/或辅助治疗相关的在成人和/或儿童中最常报告的不良事件是嗜睡、头晕、头痛、恶心和呕吐。奥卡西平单药治疗比苯妥英钠(在成人和儿童中)和丙戊酸(在成人中)耐受性更好,并且尽管在最近的5项单药治疗研究中75%至90%的成年患者在接受奥卡西平治疗时报告了不良事件,但因这些不良事件退出治疗的患者<8%。急性低钠血症虽通常无症状,但在用奥卡西平治疗的患者中发生率为2.7%。从卡马西平治疗转换为奥卡西平治疗时最有可能缓解的不良事件是未明确的皮肤反应(皮疹、瘙痒、湿疹)、过敏反应以及不适、头晕和头痛的组合。尽管奥卡西平确实与某些药物(如苯妥英钠和口服避孕药)有临床显著相互作用,但因其主要代谢途径由非诱导性酶介导,所以与 older antiepileptic drugs(AEDs)相比,其相互作用倾向较低。
奥卡西平作为单药治疗在治疗成人和儿童的部分性及全身强直 - 阵挛发作方面是现有抗癫痫药物的可行替代方案。此外,它作为辅助治疗在两个年龄组的难治性部分性发作治疗中也有效。另外,该药物耐受性优于 older, established AEDs,且药物相互作用可能性较低。这些特性使奥卡西平成为新诊断的部分性和全身强直 - 阵挛发作初始治疗以及成人和儿童药物难治性部分性发作辅助治疗的有效成分。