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

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From the Guidelines

Multaq (dronedarone) 400mg twice daily is not recommended as a first-line treatment for atrial fibrillation due to its association with increased mortality and safety concerns in certain patient populations. According to the European Society of Cardiology working group on cardiovascular pharmacotherapy 1, antiarrhythmic drugs like dronedarone increase the risk of bradycardia, AV block, and heart failure in patients with poor left ventricular function. Additionally, the 2016 ESC guidelines for the management of atrial fibrillation 1 suggest that amiodarone, a safer alternative, can be used as adjunctive therapy in patients where heart rate control cannot be achieved using combination therapy.

  • Key safety concerns with Multaq include:
    • Increased risk of death, stroke, and heart failure in patients with permanent atrial fibrillation or decompensated heart failure
    • Contraindication in patients with permanent atrial fibrillation, recent or current heart failure, or severe liver disease
    • Potential interactions with numerous medications, including statins, calcium channel blockers, and anticoagulants
  • Safer alternatives for atrial fibrillation management may include:
    • Amiodarone
    • Sotalol
    • Catheter ablation
    • Beta-blockers, such as bisoprolol, carvedilol, or metoprolol, which can provide symptomatic and functional improvement as a result of rate control 1 It is essential to carefully evaluate the risks and benefits of Multaq in each patient and consider alternative treatments to minimize the risk of adverse outcomes. Regular monitoring of liver function and patient education on potential side effects are crucial when prescribing Multaq.

From the FDA Drug Label

In patients with permanent atrial fibrillation, MULTAQ doubles the risk of death, stroke and hospitalization for heart failure. MULTAQ is contraindicated in patients in atrial fibrillation (AF) who will not or cannot be cardioverted into normal sinus rhythm. The recommended dosage of MULTAQ is 400 mg twice daily in adults MULTAQ should be taken as one tablet with the morning meal and one tablet with the evening meal.

The safety of Multaq 400mg BID for atrial fibrillation is a concern due to the increased risk of death, stroke, and heart failure in patients with permanent atrial fibrillation. Multaq is contraindicated in patients with permanent atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm. The recommended dosage is 400mg twice daily, and it should be taken with meals. Key considerations include:

  • Contraindications: permanent atrial fibrillation, symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms
  • Warnings and precautions: cardiovascular death, heart failure, stroke, liver injury, QT interval prolongation
  • Adverse reactions: diarrhea, nausea, abdominal pain, vomiting, asthenia, bradycardia, skin and subcutaneous tissue disorders 2 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 effective in preventing atrial fibrillation recurrence and reducing cardiovascular hospitalization or death from any cause 4, 6, 7.
  • However, dronedarone has also been associated with adverse effects such as diarrhea, nausea, vomiting, and cutaneous disorders 3.
  • There have been concerns about the potential long-term adverse effects of dronedarone, including pulmonary fibrosis 3.
  • A study published in 2014 found that dronedarone was not associated with an increased risk of death or liver disease in patients with atrial fibrillation 5.
  • Another study published in 2019 found that dronedarone had a similar liver safety profile to other antiarrhythmics and that liver toxicity could be equally common with many Class III antiarrhythmics 7.
  • The use of dronedarone in patients with severe or deteriorating heart failure is contraindicated due to increased mortality risk 6, 7.
  • Real-world data suggest that dronedarone significantly reduces AF burden and cardiovascular hospitalizations, and demonstrates a low risk for proarrhythmia in patients with paroxysmal or persistent AF 7.

Adverse Effects

  • Common adverse effects of dronedarone include:
    • Diarrhea
    • Nausea
    • Vomiting
    • Cutaneous disorders
  • Less common adverse effects include:
    • Bradycardia
    • QT prolongation
    • Transient elevation of creatinine levels
    • Renal failure
  • Rare but serious adverse effects include:
    • Pulmonary fibrosis
    • Liver toxicity

Interactions with Other Medications

  • Dronedarone has been shown to interact with certain medications, including:
    • Digoxin: increased mortality risk due to pharmacokinetic interaction 7
    • Direct oral anticoagulants: no significant safety risks reported with apixaban and edoxaban, but PK data on rivaroxaban interaction are unavailable 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Dronedarone: an overview.

Annals of medicine, 2012

Research

Safety of dronedarone in routine clinical care.

Journal of the American College of Cardiology, 2014

Research

Safety and efficacy of dronedarone from clinical trials to real-world evidence: implications for its use in atrial fibrillation.

Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology, 2019

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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