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

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From the Guidelines

Multaq (dronedarone) 400mg twice daily should be used with caution in patients with atrial fibrillation due to its potential to increase the risk of bradycardia, heart failure, and liver toxicity, as highlighted in the 2022 European Heart Journal review 1.

Safety Concerns

The use of Multaq in patients with atrial fibrillation is associated with several safety concerns, including:

  • Increased risk of bradycardia and heart failure, particularly in patients with pre-existing heart disease
  • Potential for liver toxicity, which requires regular monitoring of liver function
  • Interactions with other medications, such as warfarin, digoxin, and statins, which may require dose adjustments

Patient Selection

Multaq should only be used in patients with paroxysmal or persistent atrial fibrillation who have returned to normal sinus rhythm, and not in patients with permanent atrial fibrillation. It is contraindicated in patients with severe heart failure, recent decompensated heart failure, or left ventricular systolic dysfunction, as it can increase mortality in these populations.

Monitoring and Dose Adjustments

Regular monitoring of liver function, especially during the first six months of treatment, is necessary to minimize the risk of liver toxicity. Patients should also be monitored for signs of bradycardia and heart failure, and the dose of Multaq should be adjusted accordingly. The doses of concomitant medications, such as digoxin and warfarin, should also be reduced upon initiation of Multaq to minimize the risk of interactions.

Alternative Treatments

Multaq is typically a second-line option for the treatment of atrial fibrillation, and other antiarrhythmic medications, such as amiodarone, flecainide, and propafenone, may be preferred due to their more favorable safety profiles, as outlined in the 2011 Circulation guidelines 1.

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

The safety of Multaq 400mg BID for atrial fibrillation is a concern, as it doubles the risk of death, stroke, and hospitalization for heart failure in patients with permanent atrial fibrillation. Additionally, Multaq is contraindicated in patients with permanent atrial fibrillation who will not or cannot be cardioverted into normal sinus rhythm. Therefore, Multaq 400mg BID should be used with caution in patients with atrial fibrillation, and only in those who can be cardioverted into normal sinus rhythm 2.

From the Research

Safety of Multaq 400mg BID for Atrial Fibrillation

  • The safety of Multaq (dronedarone) 400mg BID for atrial fibrillation has been evaluated in several studies 3, 4, 5, 6, 7.
  • A study published in the Journal of Atrial Fibrillation found that dronedarone was associated with a lower risk of cardiovascular events, stroke, and congestive heart failure compared to amiodarone in patients without a history of congestive heart failure 3.
  • Another study published in Prescrire International noted that dronedarone was better tolerated but less effective than amiodarone in the short term, and that little is known about its potential long-term adverse effects 4.
  • A study published in the Journal of the American College of Cardiology found that dronedarone was not associated with an increased risk of mortality or liver disease in patients with atrial fibrillation 5.
  • A review of clinical trials and real-world evidence published in Europace found that dronedarone was effective in reducing the risk of hospitalization in patients with paroxysmal or persistent atrial fibrillation, and that its safety profile was similar to other antiarrhythmics 7.
  • The same review noted that concerns about liver safety and mortality risk in patients with permanent atrial fibrillation should be balanced against the significant reduction in hospitalizations and low risk of proarrhythmias following dronedarone treatment 7.

Adverse Effects

  • Common adverse effects of dronedarone include gastrointestinal disorders, diarrhea, nausea, vomiting, and cutaneous disorders 4.
  • Dronedarone has also been associated with a risk of liver toxicity, although recent real-world evidence suggests that this risk is similar to other antiarrhythmics 7.
  • The risk of proarrhythmia with dronedarone is low in patients with paroxysmal or persistent atrial fibrillation 7.

Interactions with Other Medications

  • Dronedarone has been shown to interact with certain medications, including digoxin, which may increase the risk of mortality 7.
  • The safety of combining dronedarone with direct oral anticoagulants such as apixaban, edoxaban, and dabigatran has been evaluated in real-world studies and clinical trials, and no significant safety risks have been found 7.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Safety of dronedarone in routine clinical care.

Journal of the American College of Cardiology, 2014

Research

Dronedarone for atrial fibrillation: How does it compare with amiodarone?

Cleveland Clinic journal of medicine, 2011

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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