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

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Last updated: May 12, 2025 • View editorial policy

From the Guidelines

Multaq (dronedarone) 400mg twice daily should not be used in patients with permanent atrial fibrillation or significant cardiovascular disease burden due to increased risk of cardiovascular events and mortality, as evidenced by the PALLAS trial 1. When considering the use of Multaq for atrial fibrillation management, it is crucial to assess the patient's specific condition and medical history. The medication is indicated for the treatment of paroxysmal or persistent atrial fibrillation, but its use is contraindicated in patients with permanent atrial fibrillation, unstable hemodynamic conditions, or a history of heart failure. Key points to consider include:

  • Contraindications: permanent atrial fibrillation, unstable hemodynamic conditions, history of heart failure, or left ventricular dysfunction 1
  • Important safety considerations: increased risk of cardiovascular events, including stroke, myocardial infarction, and cardiovascular death, particularly in patients with significant cardiovascular disease burden
  • Monitoring requirements: regular assessment of liver function, particularly during the first six months of treatment, and careful monitoring for signs of heart failure or other adverse effects
  • Potential interactions: Multaq can interact with various medications, including those metabolized by CYP3A4, and may increase levels of certain drugs like digoxin and statins
  • Side effects: common adverse effects include gastrointestinal issues, fatigue, and skin reactions The European Summary of Product Characteristics for dronedarone advises that its management be supervised by a specialist, and it should not be initiated in general or family practice 1. Overall, while Multaq can be a useful medication for managing atrial fibrillation in certain patients, its use requires careful consideration of the potential risks and benefits, as well as close monitoring to minimize adverse effects.

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 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 due to the increased risk of:

  • Death
  • Stroke
  • 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 2. It is essential to carefully evaluate the patient's condition and consider the potential risks before initiating Multaq therapy. Key considerations include:
  • Cardioversion: Patients should be cardioverted into normal sinus rhythm before starting Multaq.
  • Monitoring: Patients treated with Multaq should undergo monitoring of cardiac rhythm no less often than every 3 months.
  • Contraindications: Multaq is contraindicated in patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms, and in patients with permanent 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 of Multaq (dronedarone) 400mg bid for atrial fibrillation has been evaluated in several studies 3, 4, 5, 6, 7.
  • Dronedarone is an analogue of amiodarone, designed to cause fewer adverse effects than the parent compound 3.
  • Studies have shown that dronedarone is safer than amiodarone, but less effective 3.
  • A real-world investigation found no difference in risk between dronedarone, sotalol, and propafenone initiators for cardiovascular events, stroke, congestive heart failure, interstitial lung disease, and acute liver injury 4.
  • Amiodarone was associated with a higher risk of cardiovascular events, stroke, and congestive heart failure than dronedarone in patients without a congestive heart failure history 4.
  • High-certainty evidence from a systematic review suggested that dronedarone may be associated with reduced risk of stroke 5.
  • Dronedarone was found to have a lower risk of proarrhythmic effects compared to other antiarrhythmic drugs, including amiodarone and sotalol 5.
  • A comparative effectiveness study found that dronedarone had similar efficacy to dofetilide, but was less effective than amiodarone, class 1C agents, and sotalol for rhythm control of atrial fibrillation 6.
  • A random controlled clinical study found that amiodarone was more effective than sotalol in maintaining sinus rhythm, with fewer adverse reactions 7.

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.