Dronedarone (Multaq®)
| Dronedarone |  |
|---|---|
| Brand Name | Multaq® |
| Drug Class | Class III Antiarrhythmic |
| Vaughan-Williams Class | Class III (Multichannel Blocker) |
| Primary Indication | Atrial Fibrillation / Atrial Flutter |
| QT Prolongation | Yes |
| Iodine Content | No |
| Half-Life | ~24 hours |
| Black Box Warning | Heart Failure Risk |
| FDA Approval | 2009 |
Overview
Dronedarone is a multichannel antiarrhythmic agent structurally related to Amiodarone but without iodine moieties.
It is used for rhythm control in paroxysmal or persistent atrial fibrillation (AF) and atrial flutter (AFL).
Compared to amiodarone, dronedarone has fewer thyroid and pulmonary toxicities but is less effective and carries a boxed warning in patients with heart failure.
Mechanism of Action
Dronedarone blocks multiple cardiac ion channels:
- Potassium channels → ↑ action potential duration → ↑ QT interval
- Sodium channels
- Calcium channels
- Noncompetitive β-adrenergic receptor antagonism
Net effects:
- Prolonged repolarization
- Slowed AV nodal conduction
- Reduced AF recurrence
Mechanistically similar to amiodarone but with shorter half-life and less tissue accumulation.
Indications
- Paroxysmal atrial fibrillation
- Persistent atrial fibrillation
- Atrial flutter
Goal:
- Reduce hospitalization in AF
Not indicated for:
- Permanent AF
- Ventricular arrhythmias
Black Box Warning
Dronedarone increases risk of death in:
- Symptomatic heart failure (NYHA Class III or IV)
- Recently decompensated heart failure
- Permanent atrial fibrillation
Avoid in these populations.
Contraindications
Absolute:
- Symptomatic heart failure
- Permanent atrial fibrillation
- Second- or third-degree AV block (without pacemaker)
- Severe hepatic impairment
- QTc ≥ 500 ms
Relative / Caution:
- Bradycardia
- Electrolyte abnormalities
- Concomitant QT-prolonging drugs
Dosing
- 400 mg orally twice daily with meals
No loading dose required.
Pharmacokinetics
Absorption:
- Oral; increased with food
Metabolism:
- Hepatic (CYP3A4)
Half-life:
- ~24 hours
Elimination:
- Primarily fecal
Shorter half-life and less tissue accumulation than amiodarone.
Adverse Effects
Common:
- Nausea
- Diarrhea
- Bradycardia
Serious:
- QT prolongation
- Hepatotoxicity
- Heart failure exacerbation
Lower risk of:
- Thyroid toxicity (no iodine)
- Pulmonary fibrosis
Compared to Amiodarone.
Drug Interactions
CYP3A4 inhibitors (↑ levels):
- Azoles
- Macrolides
- Protease inhibitors
QT-prolonging agents:
- Fluoroquinolones
- Other Class III antiarrhythmics
Digoxin:
- Increases digoxin levels
Warfarin:
- May increase INR
Monitoring
- ECG (QT interval)
- Liver function tests
- Heart failure symptoms
- Electrolytes
Discontinue if patient develops permanent AF.
Clinical Pearls
- Structurally similar to amiodarone but lacks iodine.
- Less effective than amiodarone.
- Fewer thyroid and pulmonary toxicities.
- Contraindicated in symptomatic heart failure.
- Not used for ventricular arrhythmias.
Comparison Within Class
Compared to Amiodarone:
- Less effective
- Fewer organ toxicities
- Shorter half-life
Compared to Sotalol:
- Multichannel blockade vs β-blocker + K channel block
- No renal dosing requirement
Compared to Dofetilide:
- No inpatient loading required
- Lower torsades risk