Should 800mg of amiodarone be administered as a single dose or split into divided doses?

Amiodarone 800mg Oral Dosing: Split into Divided Doses

The 800mg oral dose of amiodarone must be split into divided doses throughout the day, not given as a single dose. 1

Guideline-Based Dosing Recommendations

For Ventricular Arrhythmias

• Administer 800-1,600 mg per day in divided doses until a total of 10 grams has been given, then reduce to maintenance dosing of 200-400 mg per day 1
• The divided dosing approach is explicitly specified in American Family Physician guidelines for oral inpatient treatment 1

For Atrial Fibrillation

• Use 600-800 mg per day in divided doses until a total of 10 grams has been administered, followed by 200 mg per day maintenance 1
• This applies to both inpatient and outpatient settings 1

Specific Loading Regimens

• The American Heart Association recommends 400-600 mg daily in divided doses for 2-4 weeks as a standard loading approach, followed by maintenance of 100-200 mg daily 2
• Higher loading doses up to 1,200 mg daily may be considered in monitored inpatient settings, but these must also be divided 2

Rationale for Divided Dosing

Divided dosing minimizes gastrointestinal side effects, which are extremely common with amiodarone therapy 1

• Gastrointestinal upset and constipation occur frequently and are dose-related adverse effects 1
• In one study, 56 of 70 patients (80%) experienced gastrointestinal side effects, most commonly constipation 3

The divided approach helps reduce peak plasma concentrations that contribute to acute adverse effects while maintaining therapeutic levels 4

Critical Monitoring During Loading

• Watch for bradycardia, QT prolongation, and heart block during the loading phase 1, 2
• Continuous ECG monitoring is mandatory when initiating therapy, particularly with higher loading doses 5
• Drug-related bradycardia occurs in 4.9% of patients, though this statistic applies primarily to IV administration 5

Common Pitfalls to Avoid

Do not give 800mg as a single daily dose - this contradicts established guidelines and increases the risk of gastrointestinal intolerance 1

Reduce maintenance doses as soon as possible - the goal is to use the lowest effective dose to minimize toxicity, as side effects are dose-dependent and occur in up to 93% of patients on long-term therapy 3

Account for amiodarone's extremely long half-life (average 58 days, range 15-100 days) - therapeutic effects may take days to weeks to develop despite adequate loading 2, 6