FDA Approved Drugs » 2009
Medical Areas: Cardiology/Vascular Diseases
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approval Status: Approved July 2009
Treatment Area: paroxysmal or persistent atrial fibrillation or atrial flutter
Multaq (dronedarone) is a benzofuran derivative with antiarrhythmic properties belonging to all four Vaughan-Williams classes. The exact mechanism of action is unknown.
Multaq is specifically indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors who are in sinus rhythm or who will be cardioverted.
Multaq is supplied as a 400mg tablet designed for oral administration. The recommended initial dose of the drug is 400 mg twice daily, once in the morning with a meal and once in the evening with a meal.
The FDA approval of Multaq was based on the results of three studies:
This multicenter, multinational, double blind, and randomized placebo-controlled study enrolled 4,628 patients with a recent history of AF/AFL who were in sinus rhythm or who were to be converted to sinus rhythm. The subjects were at least 75 years old or at least 70 years old with one risk factor. They were randomized and treated for up to 30 months with either Multaq 400 mg twice daily or placebo, in addition to conventional therapy for cardiovascular diseases. The primary endpoint, time to first hospitalization for cardiovascular reasons or death from any cause, was significantly decreased in the Multaq arm (by 24%) versus placebo (p=0.00000002). Several secondary endpoints were reached as well, including a significant decrease in the risk of cardiovascular death by 30% (p=0.03) with Multaq plus standard therapy. Multaq also significantly decreased the risk of arrhythmic death by 45% (p=0.01) and there were numerically fewer deaths (16%) from any cause in the Multaq group compared to placebo (p=0.17). First cardiovascular hospitalization was reduced by 25% (p=0.000000009).
EURIDIS and ADONIS
These two studies enrolled 1,237 subjects (20 to 88 years) in sinus rhythm with a prior episode of AF or AFL. The subjects were randomized in an outpatient setting and treated with either Multaq 400 mg twice daily or placebo on top of conventional therapies. All subjects had at least one ECG-documented AF/AFL episode during the 3 months prior to study entry but were in sinus rhythm for at least one hour. In the pooled data, as well as in the individual trials, dronedarone delayed the time to first recurrence of AF/AFL (primary endpoint), lowering the risk of first AF/AFL recurrence during the 12-month study period by about 25%, with an absolute difference in recurrence rate of about 11% at 12 months.
Adverse events associated with the use of Multaq may include, but are not limited to, the following:
- Asthenic conditions
- Skin infections
- Abdominal pain
Mechanism of Action
Multaq (dronedarone) is a benzofuran derivative with antiarrhythmic properties belonging to all four Vaughan-Williams classes. The exact mechanism of action is unknown. Dronedarone is a derivative of amiodarone, an effective yet toxic antiarrhythmic drug. Unlike amiodarone, dronedarone does not contain idodine atoms and hence contains the efficacy of amiodarone but without its unique toxicity profile.
Floyd J Dronedarone in atrial fibrillation. The New England Journal of Medicine 2009 Jun 4;360(23):2480
Krishnamoorthy S, Lip GY Antiarrhythmic drugs for atrial fibrillation: focus on dronedarone. Expert Review of Cardiovascular Therapy 2009 May;7(5):473-81
Hohnloser SH, Crijns HJ, van Eickels M, Gaudin C, Page RL, Torp-Pedersen C, Connolly SJ; ATHENA Investigators Effect of dronedarone on cardiovascular events in atrial fibrillation. New England Journal of Medicine 2009 Feb 12;360(7):668-78
Davy JM, Herold M, Hoglund C, Timmermans A, Alings A, Radzik D, Van Kempen L; ERATO Study Investigators Dronedarone for the control of ventricular rate in permanent atrial fibrillation: the Efficacy and safety of dRonedArone for the cOntrol of ventricular rate during atrial fibrillation (ERATO) study. American Heart Journal 2008 Sep;156(3):527.e1-9.
Singh BN, Connolly SJ, Crijns HJ, Roy D, Kowey PR, Capucci A, Radzik D, Aliot EM, Hohnloser SH; EURIDIS and ADONIS Investigators Dronedarone for maintenance of sinus rhythm in atrial fibrillation or flutter. New England Journal of Medicine 2007 Sep 6;357(10):987-99
Touboul P, Brugada J, Capucci A, Crijns HJ, Edvardsson N, Hohnloser SH Dronedarone for prevention of atrial fibrillation: a dose-ranging study. European Heart Journal 2003 Aug;24(16):1481-7
For additional information regarding Multaq or paroxysmal or persistent atrial fibrillation or atrial flutter, please visit the Multaq