Rudd G D, Haverkamp W, Mason J W, Wenger T, Jay G, Hebert D, Doty P, Horstmann R
Department of Cardiology, Campus Virchow Clinic, Charite'-University Medicine Berlin, Berlin, Germany.
Cardiology Division, Department of Medicine, University of Utah, Salt Lake City, UT, USA.
Acta Neurol Scand. 2015 Nov;132(5):355-63. doi: 10.1111/ane.12414. Epub 2015 Apr 30.
To evaluate the cardiac safety of adjunctive lacosamide in a large pool of adults with partial-onset seizures (POS).
Post-randomization changes from baseline for electrocardiographic (ECG) measurements, diagnostic findings, and relevant adverse events (AEs) were compared for pooled data from three randomized, placebo-controlled trials of adjunctive lacosamide for the treatment of POS.
Lacosamide did not prolong the QTc interval or affect heart rate as determined by an analysis of data from patients randomized to lacosamide 200, 400, or 600 mg/day (n = 944) compared with placebo (n = 364). After 12-week maintenance treatment, mean changes from baseline for QRS duration were similar between the placebo and lacosamide 200 and 400 mg/day groups (0.0, -0.2, and 0.4 ms), but slightly increased for lacosamide 600 mg/day (2.3 ms). A small, dose-related mean increase in PR interval was observed (-0.3, 1.4, 4.4, and 6.6 ms for the placebo and lacosamide 200, 400, and 600 mg/day groups, respectively). First-degree atrioventricular (AV) block was reported as a non-serious AE in 0.0%, 0.7%, 0.2%, and 0.5% of patients in the same respective groups. Second- or higher degree AV block was not observed. There was no evidence of a PR-interval-related pharmacodynamic interaction of lacosamide with either carbamazepine or lamotrigine.
Evaluation of the pooled cardiac safety data from patients with POS showed that adjunctive lacosamide at the maximum recommended dose (400 mg/day) was not clearly associated with any cardiac effect other than a small, dose-related increase in PR interval that had no evident symptomatic consequence.
评估在大量成人部分性发作（POS）患者中添加拉科酰胺的心脏安全性。
对三项用于治疗POS的拉科酰胺辅助治疗的随机、安慰剂对照试验的汇总数据，比较随机分组后心电图（ECG）测量、诊断结果及相关不良事件（AE）相对于基线的变化。
与安慰剂组（n = 364）相比，对随机接受200、400或600 mg/天拉科酰胺治疗的患者（n = 944）的数据进行分析，结果显示拉科酰胺未延长QTc间期或影响心率。12周维持治疗后，安慰剂组与200和400 mg/天拉科酰胺组的QRS时限相对于基线的平均变化相似（分别为0.0、-0.2和0.4 ms），但600 mg/天拉科酰胺组略有增加（2.3 ms）。观察到PR间期有与剂量相关的小幅平均增加（安慰剂组及拉科酰胺200、400和600 mg/天组分别为-0.3、1.4、4.4和6.6 ms）。在相同的各治疗组中，分别有0.0%、0.7%、0.2%和0.5%的患者报告一度房室（AV）阻滞为非严重不良事件。未观察到二度或更高程度的AV阻滞。没有证据表明拉科酰胺与卡马西平或拉莫三嗪存在与PR间期相关的药效学相互作用。
对POS患者汇总心脏安全性数据的评估表明，最大推荐剂量（400 mg/天）的辅助拉科酰胺除了使PR间期有与剂量相关的小幅增加且无明显症状后果外，与任何心脏效应均无明确关联。
