ST LOUIS (MD Consult) - On July 2, 2009, the US Food and Drug Administration (FDA) approved Multaq (dronedarone) for use in patients with a history of atrial fibrillation (AF) or atrial flutter (AFL). Multaq is an antiarrhythmic agent indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent AF or AFL who are now in sinus rhythm. It is also indicated for use in patients with these arrhythmias who are planning to undergo cardioversion. Candidates for whom Multaq therapy may be considered should also have associated cardiovascular risk factors, such as hypertension, diabetes, prior cerebrovascular accident, or age older than 70 years, or have a left atrial diameter measurement ≥50 mm or a left ventricular ejection fraction of <40%.

 

Sanofi-aventis, Multaq's manufacturer, states that the drug's FDA approval was granted on the basis of data from 5 international, multicenter, randomized clinical trials involving nearly 6,300 patients. The purpose of one of these trials was to evaluate the efficacy and safety of Multaq in patients with either AF or AFL, or with a recent history of either of these arrhythmias. In this study population, 71% had no heart failure whereas 29% were in a state of stable New York Heart Association (NYHA) class I-III heart failure. The results of this trial showed that the use of Multaq 400 mg twice daily, in addition to standard therapy, reduced the combined end point of cardiovascular hospitalization or death from any cause by 24% (P < .001) compared with placebo. Patients taking Multaq had higher rates of diarrhea, nausea, bradycardia, QT-interval prolongation, and cutaneous rash than patients taking placebo.

 

Another clinical trial involved 4,628 patients with AF or AFL. In this trial, more than 2,300 patients received Multaq combined with standard therapy. The results showed a 24% reduction in the time to first cardiovascular hospitalization or all-cause mortality (P < .001) in patients receiving Multaq compared with patients taking placebo, meeting the study's primary end point.

Initiation of Multaq treatment is contraindicated in patients with severe heart failure (NYHA class IV), or with NYHA class II or III heart failure and recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. This unstable population corresponds to the population of participants in another Multaq clinical trial in which patients receiving dronedarone experienced a more than 2-fold increase in mortality compared with those receiving placebo. (This study was prematurely terminated.) Multaq may cause critical adverse reactions, including death, in patients with recent severe heart failure.

 

The intended dosage of Multaq is one 400-mg tablet taken twice daily with morning and evening meals. Treatment with Multaq can be initiated in an outpatient setting.

The most commonly reported adverse reactions with Multaq therapy include diarrhea, nausea, vomiting, abdominal pain, asthenia, and cutaneous rash.

圣路易斯(MD Consult)——2009年7月2日，美国食品药品管理局(FDA)批准Multaq(决奈达隆)用于房颤(AF)或房扑(AFL)患者的治疗。Multaq是一种抗心律失常药，对于存在阵发性或持续性AF或AFL且目前为窦性心律的患者，该药可降低其心血管事件住院风险。Multaq亦适用于存在上述心律失常且拟行心脏复律的患者。同时存在下列相关的心血管危险因素时可考虑用Multaq治疗：高血压、糖尿病、脑血管意外病史、年龄在70岁以上、左房直径测量值≥50 mm或左室射血分数<40%。

Multaq生产厂家赛诺菲-安万特公司表示，FDA批准该药是基于5项国际、多中心、随机临床试验的结果，受试者近6,300例。其中一项试验旨在对患有AF或AFL、或者近期有上述其中一种心律失常发作史的患者应用Multaq治疗的有效性和安全性进行评价。在此受试群体中，71%无心力衰竭，而29%处于纽约心脏协会(NYHA)分级 I~III级心力衰竭稳定状态。该试验结果表明，与安慰剂对照组相比，标准治疗+Multaq用药(400 mg，1日2次)能使心血管事件住院或全因死亡联合终点降低24%(P < 0.001)。服用Multaq的患者下列事件的发生率高于安慰剂对照组：腹泻、恶心、心动过缓、QT间期延长、皮疹。

还有一项临床试验纳入了4,628例AF或AFL患者，其中逾2,300例接受Multaq联合标准治疗方案。其结果显示，与安慰剂对照组相比，Multaq治疗组患者首次心血管事件住院时间或全因死亡率减少24%(P < 0.001)，达到研究的主要终点。

患者存在下列情况时禁用Multaq：严重心力衰竭(NYHA分级IV级)，或者NYHA分级II级或III级且近期出现失代偿需住院治疗或转诊至心力衰竭专科医院。此不稳定患者群体与另一项Multaq临床试验的受试者群体情况相当。在后一试验中，接受决奈达隆治疗的患者死亡率较安慰剂对照组增加2成以上 (该研究提前被终止)。Multaq可导致死亡(见于近期发生严重心力衰竭的患者)等严重不良事件。

Multaq的预期剂量为400 mg片剂，每次1片，1日2次，早餐和晚餐后服用。门诊患者亦可接受Multaq治疗。

Multaq最常报告的不良事件为腹泻、恶心、呕吐、腹痛、乏力及皮疹等。