What is the recommended loading dose of amiodarone?

Amiodarone Loading Dose

For oral amiodarone loading, start with 800-1600 mg daily in divided doses until a total of 10 grams has been administered (typically 2-4 weeks), then transition to maintenance therapy of 200-400 mg daily. 1

Oral Loading Regimens by Indication

Ventricular Arrhythmias

• Begin with 800-1600 mg per day in divided doses until reaching a cumulative total of 10 grams, followed by maintenance of 200-400 mg daily 1, 2
• Higher loading doses (up to 1200 mg daily) may be used in monitored inpatient settings, though this increases adverse effect risk 1
• The American Heart Association's more conservative approach uses 400-600 mg daily for 2-4 weeks, then 100-200 mg maintenance 1

Atrial Fibrillation

• Use 600-800 mg per day in divided doses until 10 grams total is given, then reduce to 200 mg daily maintenance 1, 2
• This lower loading dose compared to ventricular arrhythmias reflects the less immediately life-threatening nature of atrial fibrillation 1

Intravenous Loading Protocol

For life-threatening arrhythmias requiring immediate treatment, administer 150 mg IV over 10 minutes, followed by 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours (approximately 1000 mg total in first 24 hours) 2, 3

IV Administration Requirements

• Must use volumetric infusion pump, not drop counters (which can underdose by up to 30%) 3
• Administer through central venous catheter whenever possible 3
• Concentrations >2 mg/mL require central line to avoid peripheral vein phlebitis 3
• Use in-line filter during administration 3
• Infusions >2 hours must be in glass or polyolefin bottles with D5W 3

Breakthrough Arrhythmias on IV

• Give 150 mg supplemental bolus in 100 mL D5W over 10 minutes 3
• May increase maintenance infusion rate cautiously 3
• Mean daily doses >2100 mg associated with increased hypotension risk 3

Transitioning from IV to Oral

The transition dose depends on duration of IV therapy: 1, 2

• <1 week IV: Start 800-1600 mg oral daily
• 1-3 weeks IV: Start 600-800 mg oral daily
• >3 weeks IV: Start 400 mg oral daily

Continue oral loading until 10 grams total administered, then switch to maintenance 2

Critical Monitoring During Loading

Cardiovascular Monitoring

• Watch for bradycardia (occurs in 1-3% oral, 4.9% IV) 2
• Monitor for QT prolongation (common but rarely causes torsades) 2
• Check for hypotension (16% with IV) 2
• Assess for heart block and AV conduction delays 1, 2

Laboratory and Clinical Surveillance

• Baseline and serial thyroid function tests (dysfunction occurs in 3-6% of patients) 1, 4
• Liver enzymes (hepatotoxicity risk, especially with rapid IV loading) 1, 3
• Pulmonary function and chest imaging if respiratory symptoms develop (pulmonary toxicity in 5% of patients) 1, 5
• Ophthalmologic examination (corneal microdeposits occur in nearly 100% but are usually asymptomatic) 4

Electrolyte Optimization

• Correct hypokalemia and hypomagnesemia before loading 2
• These deficiencies increase risk of QT prolongation and arrhythmias 2

Pharmacokinetic Considerations

Amiodarone has an extremely long half-life (14-58 days after chronic therapy), and full antiarrhythmic effect may take days to weeks despite adequate serum levels 1, 6

• Single-dose half-life is only 5-20 hours, but accumulation occurs with chronic dosing 6
• Bioavailability ranges from 22-86%, contributing to interindividual variability 6
• Large volume of distribution with extensive tissue accumulation 6

Common Pitfalls and Adverse Effects

High Incidence of Side Effects

• 93% of patients develop side effects, with 10-19% requiring discontinuation 4, 5
• Gastrointestinal effects (constipation, nausea) are most common, occurring in 56-80% 4, 5
• Neurologic effects (tremor, ataxia) occur in 35-52% of patients 4, 5

Serious Toxicities

• Pulmonary toxicity (5-7% of patients) can be life-threatening 1, 4, 5
• Thyroid dysfunction (3-6%) requires ongoing monitoring 1, 4, 5
• Hepatotoxicity, particularly with rapid IV loading at high concentrations 3
• Cutaneous photosensitivity and blue-gray skin discoloration (32-46%) 4

Drug Interactions Requiring Dose Adjustment

• Warfarin: Amiodarone reduces clearance, causing sudden INR increases—reduce warfarin dose by 30-50% 2
• Digoxin: Levels typically double—reduce digoxin dose by 50% 2
• Avoid coadministration with other QT-prolonging drugs without expert consultation 1

Dose Adjustment Strategy

Because virtually all patients develop side effects at 600 mg daily maintenance, plan to reduce to 200-400 mg daily after loading 4, 5

• In clinical studies, doses decreased from 572 mg/day at 45 days to 372 mg/day at 6 months due to side effects 4
• Adjust based on clinical response and adverse effect profile 5
• Lower maintenance doses (200-400 mg) maintain efficacy while reducing toxicity 1, 5