Spencer C M, Noble S
Adis International Limited, Auckland, New Zealand.
Drugs Aging. 1998 Nov;13(5):391-411. doi: 10.2165/00002512-199813050-00005.
Rivastigmine (SDZ ENA 713) is a carbamylating, long-acting reversible and noncompetitive carbamate acetylcholinesterase inhibitor that is indicated as an oral treatment for patients with mild to moderately severe Alzheimer's disease. The drug has been evaluated for this use in 3 well designed, adequately powered, phase II/III, 26-week clinical trials that included a total of 1479 rivastigmine and 647 placebo recipients. Most of these patients had concomitant disorders that were being treated with numerous other drugs. Individual and pooled results of these trials indicate that rivastigmine 6 to 12 mg/day usually produces cognitive, global and functional changes that indicate significantly less deterioration than was observed with placebo in patients with mild to moderately severe Alzheimer's disease. Individual results of the 2 pivotal trials and pooled analysis also show that, compared with placebo recipients, significantly more rivastigmine 6 to 12 mg/day recipients respond to therapy. Indeed, after 26 weeks of therapy in the 2 pivotal trials, significantly more rivastigmine 6 to 12 mg/day than placebo recipients achieved clinically meaningful improvements as defined by 3 separate response criteria. The lower dosage range of 1 to 4 mg/day was not as effective as 6 to 12 mg/day, as measured using these criteria and other efficacy parameters. Rivastigmine causes adverse events that are generally those expected from an acetylcholinesterase inhibitor. They are usually mild to moderate, of short duration and responsive to dosage reduction. Unpublished data from 3989 patients indicate that rivastigmine and placebo were associated with similar incidences of serious adverse events and changes in laboratory parameters, ECG and cardiorespiratory vital signs. The most common events were gastrointestinal, central and peripheral nervous system and whole body adverse events. However, compared with placebo, rivastigmine more commonly caused adverse events resulting in treatment withdrawal. These events were most frequently gastrointestinal and were more common in women.
Rivastigmine is a useful option for the treatment of patients with mild to moderately severe Alzheimer's disease. Although only short term (6- month) comparisons with placebo are available, given the lack of established treatment options it should be considered for first-line use in this population.
卡巴拉汀（SDZ ENA 713）是一种氨基甲酰化、长效可逆且非竞争性的氨基甲酸酯类乙酰胆碱酯酶抑制剂，适用于轻度至中度重度阿尔茨海默病患者的口服治疗。该药物已在3项设计良好、样本量充足的II/III期26周临床试验中进行了此项用途的评估，共纳入1479名接受卡巴拉汀治疗的患者和647名接受安慰剂治疗的患者。这些患者中的大多数伴有其他多种药物正在治疗的合并症。这些试验的个体和汇总结果表明，卡巴拉汀6至12毫克/天通常会产生认知、整体和功能方面的变化，表明与轻度至中度重度阿尔茨海默病患者使用安慰剂相比，病情恶化程度明显减轻。两项关键试验的个体结果和汇总分析还显示，与接受安慰剂治疗的患者相比，接受卡巴拉汀6至12毫克/天治疗的患者对治疗有反应的比例明显更高。事实上，在两项关键试验中经过26周的治疗后，按照3种不同的反应标准定义，接受卡巴拉汀6至12毫克/天治疗的患者在临床上取得有意义改善的人数明显多于接受安慰剂治疗的患者。按照这些标准和其他疗效参数衡量，1至4毫克/天的较低剂量范围不如6至1毫克/天有效。卡巴拉汀引起的不良事件通常是乙酰胆碱酯酶抑制剂所预期的那些。它们通常为轻度至中度，持续时间短，且可通过减少剂量来应对。来自3989名患者的未发表数据表明，卡巴拉汀和安慰剂的严重不良事件发生率以及实验室参数、心电图和心肺生命体征的变化相似。最常见的事件是胃肠道、中枢和外周神经系统以及全身不良事件。然而，与安慰剂相比，卡巴拉汀更常引起导致治疗中断的不良事件。这些事件最常发生在胃肠道，且在女性中更为常见。
卡巴拉汀是治疗轻度至中度重度阿尔茨海默病患者的一种有用选择。尽管目前仅有与安慰剂的短期（6个月）比较，但鉴于缺乏既定的治疗选择，在该人群中应考虑将其作为一线用药。
