What is the recommended use and dosage of Multaq (dronedarone) for patients with atrial fibrillation or atrial flutter?

Multaq (Dronedarone) for Atrial Fibrillation and Atrial Flutter

Dronedarone (Multaq) is recommended at a dosage of 400 mg twice daily for patients with paroxysmal or persistent atrial fibrillation or flutter who are in sinus rhythm, but should NOT be used in patients with permanent atrial fibrillation or heart failure. 1, 2

Indications and Dosage

• Multaq is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent atrial fibrillation 1
• The recommended dosage is 400 mg twice daily, taken as one tablet with the morning meal and one tablet with the evening meal 1
• Treatment with Class I or III antiarrhythmics must be stopped before starting dronedarone 1

Patient Selection - Who Should Receive Dronedarone

Dronedarone is appropriate for:

• Patients with paroxysmal or persistent AF after cardioversion 2
• Patients with non-permanent AF and cardiovascular risk factors 2
• Patients without significant structural heart disease as initial antiarrhythmic therapy (along with flecainide, propafenone, and sotalol) 2
• Patients with coronary artery disease (as first-line therapy, preferred over sotalol due to better safety profile) 2
• Patients with left ventricular hypertrophy (demonstrated to be safe and well tolerated) 2

Contraindications - Who Should NOT Receive Dronedarone

Dronedarone is contraindicated in:

• Patients with permanent atrial fibrillation (patients in whom normal sinus rhythm will not or cannot be restored) 2, 1
• Patients with symptomatic heart failure with recent decompensation requiring hospitalization or NYHA Class IV symptoms 2, 1
• Patients with NYHA class III and IV heart failure 2
• Patients with recently unstable (decompensation within the prior month) NYHA class II heart failure 2
• Patients with second- or third-degree AV block or sick sinus syndrome (unless they have a functioning pacemaker) 2, 1
• Patients with bradycardia <50 bpm 1
• Patients with QTc Bazett interval ≥500 ms or PR interval >280 ms 1
• Patients with severe hepatic impairment 1
• Pregnant or nursing women 1

Clinical Efficacy

• Dronedarone is more effective than placebo but less effective than amiodarone in maintaining sinus rhythm 2
• In the ATHENA trial, dronedarone reduced cardiovascular hospitalizations and all-cause mortality in patients with paroxysmal or persistent AF 2
• Dronedarone significantly reduces ventricular rate during AF recurrence compared to placebo 2, 3
• The median time to first AF recurrence was significantly longer with dronedarone compared to placebo (737 days vs. 498 days) 3
• Post-hoc analysis demonstrated a reduction in stroke risk in patients receiving dronedarone, independent of underlying antithrombotic therapy 2, 4

Monitoring and Safety Considerations

• Patients treated with dronedarone should undergo monitoring of cardiac rhythm no less often than every 3 months 1
• Cardiovert patients who are in atrial fibrillation (if clinically indicated) or discontinue dronedarone if they develop permanent AF 1
• Monitor for signs of heart failure; if heart failure develops or worsens and requires hospitalization, discontinue dronedarone 1
• Consider obtaining periodic hepatic serum enzymes, especially during the first 6 months of treatment 1
• If liver injury is suspected (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, or itching), promptly discontinue dronedarone 1
• Monitor potassium and magnesium levels, especially with concomitant administration of potassium-depleting diuretics 1
• Monitor renal function periodically (small increases in creatinine levels are expected) 1

Common Adverse Effects

• Gastrointestinal disorders: diarrhea (9%), nausea (5%), abdominal pain (4%), vomiting (2%) 1
• Asthenic conditions (7%) 1
• Bradycardia (3%) 1
• Skin reactions including rashes (5%) 1
• QTc prolongation (28% vs 19% with placebo) 1
• Early increases in creatinine ≥10% (51% vs 21% with placebo) 1

Drug Interactions

• Dronedarone is metabolized primarily by CYP3A and is a moderate inhibitor of CYP3A and CYP2D6 1
• Concomitant use with strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir) is contraindicated 1
• Avoid drugs that prolong QT interval and might increase risk of Torsade de Pointes 1
• Digoxin levels may increase when co-administered with dronedarone 1

Clinical Pearls

• Dronedarone should be initiated by specialists familiar with the use of antiarrhythmic drugs, not in general or family practice 2
• The PALLAS trial showed increased cardiovascular events with dronedarone in patients with permanent AF, leading to early termination of the trial 2
• Dronedarone offers a better safety profile than amiodarone but is less effective at maintaining sinus rhythm 2
• Patients should be in sinus rhythm when starting dronedarone and should be receiving appropriate antithrombotic therapy 1