What is the best way to load oral amiodarone (antiarrhythmic medication)?

From the Guidelines

The best way to load oral amiodarone is to start with a high dose of 800-1600 mg daily for 1-2 weeks (loading phase), followed by a maintenance dose of 200-400 mg daily. This approach is supported by the most recent and highest quality study, which recommends a loading dose of 800 mg daily for 1 week, followed by a maintenance dose of 200 mg daily 1. Specifically, a common regimen is 800 mg twice daily for 1-2 weeks, then 400 mg twice daily for 2-4 weeks, followed by a maintenance dose of 200 mg once or twice daily. Amiodarone should be taken with food to reduce gastrointestinal side effects. During the loading phase, patients should be monitored for QT prolongation, bradycardia, and other adverse effects. Baseline thyroid function tests, liver function tests, pulmonary function tests, and an eye exam are recommended before starting therapy.

• Key considerations for amiodarone loading include:
  • Monitoring for adverse effects such as QT prolongation, bradycardia, and gastrointestinal upset
  • Adjusting the dose based on patient response and tolerance
  • Considering alternative dosing regimens, such as 600-800 mg daily, for patients with certain medical conditions or concomitant medications
  • Being aware of potential drug interactions, such as with warfarin, digoxin, and other antiarrhythmic medications Amiodarone has a very long half-life (approximately 58 days) and works by blocking potassium channels, which prolongs the action potential and effective refractory period. This loading approach allows the medication to reach therapeutic tissue levels more quickly, which is important because amiodarone has a large volume of distribution and accumulates in adipose tissue and highly perfused organs. The recommended loading dose is supported by studies, including one published in 2006, which suggests that a loading dose of 800 mg daily for 1 week is effective for controlling heart rate in patients with atrial fibrillation 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Loading Protocols for Amiodarone

• The optimal loading protocol for amiodarone is not universally defined, but studies suggest that high-dose oral loading can be effective and well-tolerated in stable patients 2.
• A study comparing intravenous and oral loading versus oral loading alone found that combined intravenous and oral loading can shorten the time to optimal ventricular arrhythmia control and lower the cumulative dose required 3.
• The typical oral loading dose is 800-1200 mg/day for 7-14 days, followed by a maintenance dose of 200-400 mg/day 4.

Intravenous Loading

• Intravenous amiodarone can cause liver injury, and liver function should be monitored closely in critically ill patients 5, 6.
• A case report found that discontinuing amiodarone and using anti-inflammatory liver therapy can improve liver enzymes in patients with amiodarone-induced liver injury 5.
• The incidence of severe transaminitis due to intravenous amiodarone is low, but deaths following IV amiodarone are rarely caused by drug-induced liver failure 6.

Safety and Tolerance

• High-dose oral amiodarone loading is generally well-tolerated, but patients should be monitored for side effects such as thyroid abnormalities, pulmonary fibrosis, and transaminitis 2, 4.
• Amiodarone interacts with several medications, and clinicians should be aware of these interactions to ensure safe and effective use of the medication 4.