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

Multaq (Dronedarone) for Atrial Fibrillation and Atrial Flutter

Dosage and Administration

The recommended dosage of Multaq is 400 mg twice daily, taken with the morning and evening meals. 1

• This dosing regimen was established in the DAFNE trial, where higher doses (1200 and 1600 mg daily) provided no additional benefit and caused increased gastrointestinal side effects. 2
• All Class I or III antiarrhythmics (amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol) and strong CYP3A inhibitors must be discontinued before starting dronedarone. 1

Primary Indication

Dronedarone is indicated to reduce the risk of hospitalization for atrial fibrillation in patients in sinus rhythm with a history of paroxysmal or persistent AF. 1

• The drug is specifically designed for patients who can be maintained in sinus rhythm, not for those with permanent AF. 1
• Dronedarone reduces cardiovascular hospitalizations and all-cause mortality in appropriately selected patients, as demonstrated in the ATHENA trial involving 4,628 patients. 2, 3
• Post-hoc analysis showed a reduction in stroke risk (annual rate 1.2% vs 1.8% placebo, HR 0.66), independent of antithrombotic therapy. 2, 3

Patient Selection: Who Should Receive Dronedarone

Dronedarone is recommended as first-line therapy for patients without significant structural heart disease, alongside flecainide, propafenone, and sotalol. 2, 3

Specific Patient Populations Where Dronedarone is Appropriate:

• Coronary artery disease: Dronedarone is preferred over sotalol due to better safety profile. 3
• Left ventricular hypertrophy: Dronedarone is safe and well-tolerated in this population, unlike sotalol which carries increased proarrhythmic risk. 2, 3
• HFmrEF and HFpEF: Dronedarone is recommended for rhythm control in patients with mid-range or preserved ejection fraction heart failure. 2
• Cardiovascular risk factors: Dronedarone should be considered to reduce cardiovascular hospitalizations in patients with non-permanent AF and cardiovascular risk factors. 2, 3

Absolute Contraindications

Dronedarone is absolutely contraindicated in patients with permanent atrial fibrillation, as it doubles the risk of death, stroke, and heart failure hospitalization. 1

Critical Contraindications:

• NYHA Class IV heart failure or symptomatic heart failure with recent decompensation requiring hospitalization: Dronedarone doubles the risk of death in this population. 1, 2, 3
• NYHA Class III heart failure or recently unstable NYHA Class II heart failure: Contraindicated due to increased mortality risk. 2, 3
• Permanent atrial fibrillation: Patients who will not or cannot be cardioverted into normal sinus rhythm should never receive dronedarone. 1, 3
• Second- or third-degree AV block, sick sinus syndrome (unless pacemaker present). 1
• Bradycardia <50 bpm. 1
• QTc Bazett interval ≥500 ms or PR interval >280 ms. 1
• Severe hepatic impairment. 1
• Pregnancy (Category X) and nursing mothers. 1
• Concomitant use of strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir). 1

Comparative Effectiveness

Dronedarone is less effective than amiodarone for maintaining sinus rhythm but offers a superior safety profile without organ toxicity. 2, 3

• Amiodarone should be reserved for patients who have failed other agents or when other drugs are contraindicated, particularly in severe heart failure. 2
• Dronedarone provides both rhythm control and ventricular rate control during AF recurrence. 2, 3

Monitoring Requirements

Patients treated with dronedarone must undergo cardiac rhythm monitoring at least every 3 months. 1

• Cardiovert patients who develop atrial fibrillation (if clinically indicated) or discontinue dronedarone, as the drug offers no benefit in permanent AF. 1
• Patients should be in sinus rhythm and receiving appropriate antithrombotic therapy before initiating dronedarone. 1
• Monitor for hepatotoxicity, as dronedarone can cause severe, potentially fatal hepatic injury including acute liver failure. 4
• Maintain potassium and magnesium within normal range before and during treatment, particularly with concomitant diuretic use. 4

Important Drug Interactions

Digoxin dose must be halved when co-administered with dronedarone, with close monitoring of serum levels. 4

• Simvastatin doses >10 mg daily and lovastatin >20 mg daily are not recommended due to increased statin exposure and rhabdomyolysis risk. 4
• Dronedarone is contraindicated with dabigatran due to strong effects on plasma levels. 4
• Moderate interaction with edoxaban requires caution or dose reduction. 4

Common Adverse Effects

Gastrointestinal effects (nausea, vomiting, diarrhea) are dose-related and represent the most common reason for drug discontinuation (3.2% vs 1.8% placebo). 4

• Unlike amiodarone, dronedarone has not been associated with thyroid, pulmonary, or significant organ toxicity in clinical trials. 2
• Postmarketing cases of interstitial lung disease, pneumonitis, and pulmonary fibrosis have been reported; assess any patient with worsening dyspnea or cough promptly. 4

Initiation Considerations

Dronedarone should be initiated by specialists familiar with antiarrhythmic drugs, not in general or family practice. 3

• The PALLAS trial demonstrated increased cardiovascular events with dronedarone in permanent AF, leading to early trial termination. 3
• Dronedarone is particularly useful for reducing the risk of stroke in the first two weeks after cardioversion when stroke risk is highest. 1