Amiodarone Dosing for Atrial Fibrillation
For maintenance of sinus rhythm in atrial fibrillation, amiodarone should be initiated with a loading dose of 600 mg daily for one month (or 1000 mg daily for one week), followed by a maintenance dose of 100-400 mg daily, with most patients maintained on 200 mg daily or less to minimize toxicity. 1
Loading Dose Regimen
The standard loading approach involves two options: 1
- 600 mg per day for one month, OR
- 1000 mg per day for one week
Both regimens aim to achieve adequate tissue saturation given amiodarone's extremely long half-life (up to 100 days). 2 The loading phase is critical because the full antiarrhythmic effect may take days to weeks to develop despite adequate serum levels. 2
Alternative loading strategies include 600-800 mg daily in divided doses until a total of 10 grams has been administered, then transitioning to maintenance therapy. 2, 3 This typically requires 1-2 weeks depending on the daily dose used. 2
Maintenance Dose
After completing the loading phase, reduce to a maintenance dose of 100-400 mg daily. 1 The ACC/AHA/HRS guidelines specifically note that low-dose amiodarone (200 mg daily or less) may be effective and is associated with fewer side effects than higher-dose regimens. 1
Most patients with atrial fibrillation can be maintained on 200 mg daily. 2, 3 This lower maintenance dosing is particularly important because adverse effects are dose-related and occur in approximately 51-81% of patients on higher doses. 4, 5
Efficacy Data
Amiodarone demonstrates superior efficacy compared to other antiarrhythmic agents: 1
- 69% of patients maintained sinus rhythm with amiodarone versus 39% with propafenone or sotalol over 16 months in the CTAF study 1
- 62% remained in sinus rhythm at one year compared to 23% with class I agents in the AFFIRM study 1
- In patients with refractory atrial fibrillation, 76-79% achieved conversion to sinus rhythm, with 53-57% maintaining sinus rhythm long-term 6, 7
Patient Selection Considerations
Amiodarone is particularly appropriate as a first-line agent in patients with: 1
- Left ventricular hypertrophy (LVH)
- Heart failure
- Coronary artery disease (CAD)
- Previous myocardial infarction (MI)
In these populations, amiodarone carries a low risk of proarrhythmia compared to class I or class III agents. 1
However, amiodarone should generally be considered a second-line or last-resort agent in patients without structural heart disease due to the high incidence of potentially severe extracardiac toxic effects. 1
Monitoring Requirements
During initiation and loading: 1, 2
- Monitor heart rate approximately weekly (pulse checks, event recorders, or office ECG)
- Assess PR interval, QRS duration, and QT interval after each dose change
- Watch for bradycardia (occurs in 1-3% on oral therapy), hypotension, and AV block 2, 3
Reduce doses of concomitant medications: 1, 2
- Digoxin: reduce by 50% immediately, as amiodarone doubles digoxin levels 2, 3
- Warfarin: reduce by 30-50% and check INR within 3-5 days 2, 3
- Other rate-control agents (beta-blockers, calcium channel blockers) should be reduced as amiodarone's rate-control effect develops 1, 2
Critical Safety Considerations
Common adverse effects include: 1
- Photosensitivity
- Pulmonary toxicity (5% incidence) 4
- Polyneuropathy and tremor/ataxia (35%) 4
- Thyroid dysfunction (6%) 4
- Hepatic toxicity
- Eye complications
- Bradycardia and AV block
Approximately 18% of patients discontinue amiodarone due to side effects, with the most serious being pulmonary fibrosis, neurological toxicity, and hepatic dysfunction. 1, 5 However, torsades de pointes is rare with amiodarone compared to other antiarrhythmic agents. 1
Outpatient vs Inpatient Initiation
Amiodarone can usually be initiated safely on an outpatient basis for atrial fibrillation, even in patients with persistent AF, because it causes minimal myocardial depression and has low proarrhythmic potential. 1 However, in-hospital loading may be necessary for patients with heart failure or hemodynamic compromise related to AF. 1
Baseline requirements before outpatient initiation: 1
- Baseline uncorrected QT interval <450 ms
- Normal serum electrolytes
- Assessment of risk factors for class III drug-related proarrhythmia
Additional Benefits
Beyond rhythm control, amiodarone provides effective rate control, frequently eliminating the need for additional drugs to control ventricular rate during atrial fibrillation. 1 This dual benefit makes it particularly valuable in patients who experience breakthrough AF episodes.