What is the safety of Multaq (dronedarone) 400mg twice daily (BID) for atrial fibrillation?

From the Guidelines

Multaq (dronedarone) 400mg twice daily should be used with caution in patients with atrial fibrillation due to its potential safety concerns, particularly in those with structural heart disease or permanent atrial fibrillation, as it may increase mortality 1. When considering the use of Multaq for atrial fibrillation management, it is essential to weigh the potential benefits against the risks. The European Society of Cardiology working group on cardiovascular pharmacotherapy highlights the importance of careful consideration when prescribing antiarrhythmic drugs, including dronedarone, in older people due to the increased risk of adverse effects such as bradycardia, intracardiac conduction block, and hepatotoxicity 1. Key considerations for the use of Multaq include:

• Contraindications: severe heart failure (NYHA class IV or recent decompensation), permanent atrial fibrillation, second or third-degree heart block, bradycardia under 50 bpm, liver or lung toxicity from previous amiodarone use, QT prolongation, or severe liver impairment
• Regular monitoring: ECGs, liver function tests (especially in the first six months), and pulmonary function assessment
• Potential interactions: warfarin, digoxin, beta-blockers, calcium channel blockers, and statins, requiring dose adjustments
• Common side effects: gastrointestinal issues, fatigue, and skin reactions The 2016 ESC guidelines for the management of atrial fibrillation also emphasize the importance of careful selection of patients for rate control therapy, including the use of beta-blockers, calcium channel blockers, and cardiac glycosides 1. However, the most recent and highest quality study 1 prioritizes the safety concerns associated with Multaq, highlighting the need for cautious use in patients with atrial fibrillation.

From the FDA Drug Label

WARNING: INCREASED RISK OF DEATH, STROKE AND HEART FAILURE IN PATIENTS WITH DECOMPENSATED HEART FAILURE OR PERMANENT ATRIAL FIBRILLATION In patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure; MULTAQ doubles the risk of death. In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure. MULTAQ is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure. MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm.

The safety of Multaq 400mg BID for atrial fibrillation is a concern due to the increased risk of:

• Death
• Stroke
• Heart failure in patients with decompensated heart failure or permanent atrial fibrillation. Multaq is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV heart failure, and in patients in atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm 2.

From the Research

Safety of Multaq 400mg BID for Atrial Fibrillation

• The safety and efficacy of dronedarone, the active ingredient in Multaq, have been evaluated in several studies 3, 4, 5, 6, 7.
• Dronedarone has been shown to be associated with a lower risk of mortality and liver disease compared to other antiarrhythmic drugs 5.
• However, it has also been found to be less effective than amiodarone in maintaining normal sinus rhythm 3, 6, 7.
• The most common adverse effects of dronedarone include gastrointestinal disorders, diarrhea, nausea, vomiting, and cutaneous disorders 3.
• Dronedarone is contraindicated in severe or deteriorating heart failure 6.
• The ATHENA trial showed that dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation 6.
• A study comparing the effectiveness of antiarrhythmic drugs for rhythm control of atrial fibrillation found that amiodarone, class 1C agents, and sotalol were more effective than dronedarone 4.

Efficacy of Multaq 400mg BID for Atrial Fibrillation

• Dronedarone has been shown to be effective in reducing the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation or atrial flutter and other cardiovascular risk factors 6, 7.
• However, its efficacy is lower than that of amiodarone, and it is not recommended for patients with severe or unstable congestive heart failure 3, 6, 7.
• The DIONYSOS trial found that dronedarone was less efficient than amiodarone in maintaining normal sinus rhythm 6.

Comparison with Amiodarone

• Dronedarone is a safer alternative to amiodarone, with fewer adverse effects 3, 7.
• However, it is less effective than amiodarone in maintaining normal sinus rhythm 3, 6, 7.
• A study comparing the two drugs found that amiodarone had a higher success rate in preventing atrial fibrillation recurrence, but was associated with more adverse effects 3.