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

Recommended Dosage

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

• This dosing regimen was established in the DAFNE phase II trial and maintained across all subsequent clinical trials 2
• Food intake with dosing is required per FDA labeling 1

Indicated Patient Population

Multaq is indicated specifically to reduce the risk of hospitalization in patients with paroxysmal or persistent (non-permanent) atrial fibrillation who are currently in sinus rhythm. 1

Appropriate Candidates:

• Patients with paroxysmal or persistent AF after successful cardioversion 3
• Patients with cardiovascular risk factors including hypertension, diabetes, prior stroke/TIA, left atrial diameter ≥50 mm, LVEF <40% (but >35%), or age ≥70 years 3
• First-line option for patients with coronary artery disease (preferred over sotalol due to superior safety profile) 3
• Safe in patients with left ventricular hypertrophy 3
• Appropriate for patients without significant structural heart disease as initial antiarrhythmic therapy 3

Absolute Contraindications

Multaq is absolutely contraindicated in patients with permanent atrial fibrillation—this population experiences doubled risk of death, stroke, and heart failure hospitalization. 1

Additional Absolute Contraindications:

• NYHA Class IV heart failure or symptomatic heart failure with recent decompensation requiring hospitalization (doubles mortality risk) 1
• NYHA Class III heart failure or recently unstable Class II heart failure 3
• Second- or third-degree AV block or sick sinus syndrome (without functioning pacemaker) 1
• Bradycardia <50 bpm 1
• QTc Bazett ≥500 ms or PR interval >280 ms 1
• Concomitant strong CYP3A inhibitors (ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, ritonavir) 1
• Concomitant Class I or III antiarrhythmics 1
• Severe hepatic impairment 1
• Pregnancy (Category X) and nursing mothers 1
• Prior liver toxicity from amiodarone 1

Critical Pre-Treatment Requirements

All Class I or III antiarrhythmics must be discontinued before initiating Multaq. 1

• Verify patient is in sinus rhythm before starting therapy 1
• Ensure appropriate antithrombotic therapy is in place (stroke risk is increased in first two weeks, particularly if permanent AF develops) 1
• Correct potassium and magnesium to normal range before initiation 1
• Baseline ECG to document QTc <500 ms and PR <280 ms 1

Monitoring Requirements

Cardiac rhythm monitoring must occur at minimum every 3 months to detect conversion to permanent AF. 1

• If AF recurs: either cardiovert the patient (if clinically indicated) or discontinue Multaq 1
• Consider periodic hepatic enzyme monitoring (AST, ALT, alkaline phosphatase, bilirubin), especially during first 6 months 1
• Monitor renal function periodically (expect small reversible creatinine increase of ~0.1 mg/dL within 7 days due to tubular secretion inhibition) 1
• Discontinue immediately if QTc reaches ≥500 ms 1

Clinical Efficacy Profile

Dronedarone is more effective than placebo but less effective than amiodarone at maintaining sinus rhythm, while offering a superior safety profile compared to amiodarone. 3

• Reduces cardiovascular hospitalizations and all-cause mortality in paroxysmal/persistent AF (ATHENA trial) 3, 4, 5
• Significantly reduces ventricular rate during AF recurrence compared to placebo (mean 85.3 vs 95.5 bpm) 3, 5
• Post-hoc analysis demonstrated stroke reduction (annual rate 1.2% vs 1.8% placebo, HR 0.66) independent of antithrombotic therapy 3, 4
• Median time to first AF recurrence: 737 days with dronedarone vs 498 days with placebo 5

Critical Safety Warnings

The PALLAS trial in permanent AF patients was terminated early due to increased cardiovascular events, reinforcing the absolute contraindication in this population. 3

The ANDROMEDA trial in severe heart failure was stopped due to excess mortality in the dronedarone group. 4, 2

Common Adverse Effects:

• Gastrointestinal: diarrhea (9%), nausea (5%), abdominal pain (4%), vomiting (2%) 1
• Bradycardia (3%) 1
• Asthenia (7%) 1
• Skin reactions including rash and photosensitivity 1
• QTc prolongation (average 10 ms, but can be greater) 1

Serious Postmarketing Adverse Events:

• Hepatocellular injury including acute liver failure requiring transplant 1
• Interstitial lung disease, pneumonitis, and pulmonary fibrosis 1
• New onset or worsening heart failure 1

Initiation Guidance

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

• Women of childbearing potential must use effective contraception 1
• Instruct patients to report symptoms of hepatic injury (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine, itching) immediately 1
• Advise patients to report signs of heart failure (weight gain, edema, increasing dyspnea) 1
• If heart failure develops requiring hospitalization, permanently discontinue Multaq 1