What is Multaq (dronedarone)?

What is Multaq (Dronedarone)?

Multaq (dronedarone) is an antiarrhythmic medication approved to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent AF. 1

Drug Classification and Mechanism

Dronedarone is a benzofuran derivative structurally related to amiodarone but modified by removing the iodine moiety, making it less lipophilic and reducing the risk of organ toxicity associated with amiodarone. 2, 1

• Multichannel blocker with properties affecting all four Vaughan-Williams antiarrhythmic classes 2
• Inhibits sodium and potassium channels 2
• Exhibits non-competitive antiadrenergic activity 2
• Has calcium antagonist properties 2
• The exact mechanism by which these properties contribute to clinical effect remains unknown 1

Clinical Indications

Dronedarone is indicated for patients with paroxysmal or persistent (non-permanent) atrial fibrillation who are in sinus rhythm. 1

Appropriate Patient Populations:

• First-line option for patients without significant structural heart disease (alongside flecainide, propafenone, and sotalol) 2
• Preferred agent for patients with coronary artery disease over sotalol due to superior safety profile 3
• Safe and well-tolerated in patients with left ventricular hypertrophy 2, 3
• Appropriate for patients with cardiovascular risk factors to reduce hospitalizations 2
• Can be used in stable NYHA class I-II heart failure patients 2

Critical Contraindications

Dronedarone is absolutely contraindicated in patients with permanent atrial fibrillation. 3 The PALLAS trial was stopped early after enrolling 3,236 patients due to increased cardiovascular events and mortality in patients with permanent AF treated with dronedarone. 2

Additional Contraindications:

• NYHA class III or IV heart failure 2, 3
• Recently unstable NYHA class II heart failure (decompensation within prior month) 2, 3
• The ANDROMEDA trial was terminated early due to increased mortality from worsening heart failure in patients with severe LV dysfunction and recent hospitalization 2
• Pregnancy (Category X) - teratogenic in animal studies 1
• Nursing mothers - must discontinue nursing or the drug 1
• Severe hepatic impairment 1

Clinical Efficacy

Rhythm Control:

• More effective than placebo in maintaining sinus rhythm 2
• Less effective than amiodarone but with superior safety profile 2
• Median time to first AF recurrence: 116 days with dronedarone vs 53 days with placebo 2

Rate Control:

• Significantly reduces ventricular rate during AF recurrence 2
• Mean heart rate at first AF recurrence: 85.3 beats/min with dronedarone vs 95.5 beats/min with placebo 4

Cardiovascular Outcomes:

The ATHENA trial demonstrated significant benefits in 4,628 patients with paroxysmal or persistent AF: 2

• 24% reduction in cardiovascular hospitalization or all-cause mortality (HR 0.76, p<0.0001)
• 29% reduction in cardiovascular mortality (HR 0.71)
• Reduced stroke risk independent of antithrombotic therapy 2

Dosing and Administration

• Standard dose: 400 mg twice daily with meals 1
• Bioavailability increases from 4% (fasting) to 15% (with high-fat meal) 1
• Steady state reached within 4-8 days 1
• No dose adjustment needed for renal impairment 1
• No dose adjustment recommended for moderate hepatic impairment 1

Safety Profile Compared to Amiodarone

Dronedarone has significantly fewer thyroid, neurological, skin, and ocular adverse events compared to amiodarone. 2

• Low potential for proarrhythmia 2
• Most common side effects: gastrointestinal (nausea, vomiting, diarrhea) 5
• No evidence of thyroid, liver, or pulmonary toxicity in clinical trials 5
• Drug discontinuation: 10.4% with dronedarone vs 13.3% with amiodarone 2

Important Clinical Pearls

• Should be initiated by specialists familiar with antiarrhythmic drugs, not in general practice 3
• Less effective than amiodarone (AF recurrence 36.5% vs 24.3%) but better tolerated 2
• Extensively metabolized by CYP3A, requiring attention to drug interactions 1
• Not suitable for short-term therapy after cardioversion (unlike some other antiarrhythmics) due to its pharmacokinetic profile 2