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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 lacking 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 black box warning in patients with heart failure.
Mechanism of Action
Dronedarone blocks multiple cardiac ion channels:
- Potassium channels (prolongs repolarization → ↑ QT interval)
- Sodium channels
- Calcium channels
- Noncompetitive beta-adrenergic receptor antagonism
Net effect:
- Prolonged action potential duration
- Slowed AV nodal conduction
- Reduced risk of AF recurrence
Multichannel blockade resembles amiodarone but with shorter half-life.
Indications
- Paroxysmal atrial fibrillation
- Persistent atrial fibrillation
- Atrial flutter
Goal:
- Reduce hospitalization due to AF
Not indicated for:
- Permanent AF
- Ventricular arrhythmias
Black Box Warning
Dronedarone increases the risk of death in:
- Patients with 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; improved with food
Metabolism:
- Hepatic (CYP3A4)
Half-life:
- ~24 hours
Elimination:
- Fecal (primary)
Shorter half-life than amiodarone.
Adverse Effects
Common:
- Nausea
- Diarrhea
- Bradycardia
Serious:
- QT prolongation
- Hepatotoxicity
- Heart failure exacerbation
Less pulmonary and thyroid toxicity compared to amiodarone.
Drug Interactions
CYP3A4 inhibitors (↑ levels):
- Azoles
- Macrolides
- Protease inhibitors
QT-prolonging agents:
- Fluoroquinolones
- Other antiarrhythmics
Warfarin:
- May increase INR
Digoxin:
- Increases digoxin levels
Monitoring
- ECG (QT interval)
- Liver function tests
- Heart failure symptoms
- Electrolytes
Avoid use if patient converts to permanent AF.
Clinical Pearls
- Structurally related to amiodarone but lacks iodine.
- Fewer thyroid and pulmonary toxicities than amiodarone.
- Contraindicated in symptomatic heart failure.
- Not effective for permanent AF.
- Shorter half-life than amiodarone.
Comparison Within Class
Compared to Amiodarone:
- Less effective
- Less organ toxicity
- No iodine
- Shorter half-life
Compared to Sotalol:
- Multichannel blocker vs pure Class III + beta-blocker
- No renal dosing required
Compared to Dofetilide:
- Less torsades risk
- No inpatient loading required