From the Guidelines
Multaq (dronedarone) 400mg twice daily is not recommended for atrial fibrillation management due to significant safety concerns, including increased risks of severe liver injury, heart failure worsening, and mortality in certain patient populations. The European Society of Cardiology working group on cardiovascular pharmacotherapy highlights the potential adverse effects of antiarrhythmic drugs, including dronedarone, which can increase the risk of bradycardia, AV block, and intracardiac conduction block 1. Specifically, dronedarone can cause fatal hepatotoxicity, and its use is associated with a higher risk of proarrhythmia in patients with structural heart disease.
Key safety concerns with Multaq include:
- Severe liver injury, which can be fatal
- Worsening of heart failure, particularly in patients with NYHA Class III-IV heart failure
- Increased mortality in certain patient populations, such as those with permanent atrial fibrillation
- Common side effects, including gastrointestinal issues, fatigue, and skin reactions
- Interactions with many medications, including warfarin, digoxin, and statins, which require dose adjustments
Regular monitoring of liver function, ECG, and kidney function is essential during treatment with Multaq 1. However, given the significant safety concerns associated with this medication, other antiarrhythmic options with better safety profiles should be considered first for most patients with atrial fibrillation. The European Heart Journal study emphasizes the importance of careful consideration of the risk-benefit ratio when prescribing antiarrhythmic drugs, particularly in older adults with cardiovascular disease 1.
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 clinical trials 3, 4, 5, 6, 7.
- Dronedarone has been shown to be safer than amiodarone, but less effective in maintaining normal sinus rhythm 3, 4, 6.
- The ATHENA trial demonstrated that dronedarone significantly reduced the incidence of hospitalization due to cardiovascular events or death in high-risk patients with atrial fibrillation 5, 7.
- However, dronedarone is contraindicated in severe or deteriorating heart failure, and its use in patients with permanent atrial fibrillation has raised safety concerns 5, 7.
- Real-world evidence suggests that dronedarone's liver safety profile is similar to other antiarrhythmics, and that the risk of liver toxicity is not significantly increased 7.
- Dronedarone has been shown to have a low risk of proarrhythmia in patients with paroxysmal or persistent atrial fibrillation, and to significantly reduce AF burden and cardiovascular hospitalizations 7.
Adverse Effects
- Common adverse effects of dronedarone include gastrointestinal disorders, such as diarrhea, nausea, and vomiting, as well as cutaneous disorders and transient elevation of creatinine levels 3.
- Dronedarone has also been associated with a risk of renal failure, and cases of rapidly progressing liver failure have been reported 3, 7.
- The risk of adverse effects must be balanced against the potential benefits of dronedarone treatment, including the reduction in hospitalizations and cardiovascular events 7.
Interactions with Other Medications
- Dronedarone has been shown to interact with certain medications, including digoxin, and to affect the pharmacokinetics of direct oral anticoagulants such as apixaban and edoxaban 7.
- The use of dronedarone in combination with these medications requires careful consideration and monitoring to minimize the risk of adverse effects 7.