ST LOUIS (MD Consult) - On June 1, 2009, GlaxoSmithKline announced that the US Food and Drug Administration (FDA) has approved Lamictal XR (lamotrigine) extended-release tablets as a once-daily, add-on therapy for patients aged ≥13 years with epilepsy who experience partial-onset seizures. The safety and effectiveness of Lamictal XR have not been established in patients younger than 13 years.

The FDA approval of Lamictal XR was granted on the basis of data from an international, multicenter, randomized, double-blind, placebo-controlled trial of 236 patients aged ≥13 years with inadequately controlled partial seizures. Study participants had been receiving a stable regimen of 1 or 2 antiepileptic drugs and had experienced at least 8 partial seizures during the 8-week baseline phase of the study. Before randomization during the trial's baseline period, the patients were experiencing 4 to 6 seizures weekly.

The study's treatment period consisted of a 7-week escalation phase and a 12-week maintenance phase. Over the entire 19-week treatment period, the group assigned to once-daily Lamictal XR showed a 47% reduction in partial seizures, compared with a 25% reduction in partial seizures recorded in the placebo group (P = .0001).

In addition to the aforementioned trial, an open-label study was done to evaluate the conversion from the immediate-release form of Lamictal given twice daily to the same total daily dose of Lamictal XR given once daily. Forty-four patients with epilepsy aged ≥13 years were enrolled. Participants were divided into 3 treatment groups. Group placement depended on the type of adjunctive antiepileptic drug being taken by the patient. (The rate at which Lamictal clears the bloodstream varies depending on the other antiepileptic drugs a patient may be taking.) Study results showed that patients could be switched from the immediate-release formulation of Lamictal taken twice daily to the same total daily dose of Lamictal XR taken once daily while maintaining comparable minimum blood levels of lamotrigine, regardless of the other antiepileptic medicines being taken concurrently.

The label for Lamictal XR contains a boxed warning about the risk of serious skin rash. This risk is higher during the first 2 to 8 weeks of treatment. The risk is increased if a patient is also receiving valproic acid or divalproex sodium or is taking a higher starting dose of Lamictal XR than is prescribed. It is also increased if Lamictal XR dose escalation occurs at a faster rate than prescribed.

Patients and their caregivers and families should be informed that antiepileptic drugs increase the risk of suicidal thoughts and behavior. They should be advised to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.

Common adverse effects of Lamictal XR include dizziness, diarrhea, tremor, hot flashes, diplopia, nausea, depression, myalgia, nervousness, weakness and fatigue, and difficulty with coordination or balance. Other common adverse effects have been reported with another form of Lamictal that include headache, somnolence, and vomiting.

圣路易斯(MD Consult)——2009年6月1日，葛兰素史克公司宣布，美国食品药品管理局(FDA)已批准Lamictal XR(拉莫三嗪) 缓释片每日1次用药可作为年龄≥13岁、局部发作型癫痫症患者的添加疗法。在年龄小于13岁的患者中，该药的安全性和有效性尚未得以证实。

FDA对Lamictal XR治疗的批准是依据一项国际性、多中心、随机、双盲、安慰剂对照试验的研究结果，该试验纳入了236例年龄≥13岁、局部发作型癫痫症未得到充分控制的患者。受试者先前一直在接受一套由1至2种抗癫痫药构成的稳定用药方案，并于本研究的8周基线期至少经历了8次局部癫痫发作。在试验基线期随机化分组前，患者每周有4至6次癫痫发作。

此研究的治疗期由7周剂量递增期和12周剂量维持期构成。在整个19周的治疗期中，接受每日1次Lamictal XR用药的试验组患者局部癫痫发作减少了47％，而安慰剂组局部癫痫发作减少了25％(P=0.0001)。

除了上述试验外，还进行了一项开放标记研究，评价由每日2次Lamictal速释片转为日剂量相同、每日1次Lamictal XR用药的疗效 。44例年龄≥13岁的癫痫患者被纳入此研究并依据其服用的辅助抗癫痫药类型分成3个治疗组(Lamictal血流清除速率可因患者服用的其他抗癫痫药的不同而异)。研究结果表明，患者可以从每日服用2次Lamictal速释片转为日剂量相同、每日1次Lamictal XR用药。

Lamictal XR的标签包含一个有关严重皮疹风险的黑框警告。此风险在最初2至8周治疗期较高。若患者同时接受丙戊酸或双丙戊酸钠治疗，或者服用的Lamictal XR起始剂量高于处方剂量，该风险会增加。当Lamictal XR的剂量递增速度高于处方规定的速度时，该风险亦可增加。

应告知患者及其监护者和亲属，抗癫痫药可增加自杀意念或行为风险。因此，应建议上述人群警惕抑郁症体征和症状的出现或恶化，警惕患者情绪或行为的任何异常变化，以及自杀意念、行为或自残的征兆。

Lamictal XR常见的不良反应包括头晕、腹泻、震颤、潮热、复视、恶心、抑郁、肌肉酸痛、神经紧张、虚弱、疲劳以及协调或平衡困难。其他常见的不良反应有头痛、嗜睡以及呕吐，这在另一种Lamictal中已有报告。

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