What is the protocol for oral (per os, PO) loading of amiodarone?

Oral Amiodarone Loading Protocol

For ventricular arrhythmias, load with 800-1600 mg daily in divided doses until a cumulative total of 10 grams is reached, then transition to maintenance dosing of 200-400 mg daily. 1, 2

Loading Dose Regimens by Indication

Ventricular Arrhythmias

• Start with 800-1600 mg per day in divided doses until a total cumulative dose of 10 grams has been administered 1, 2
• This typically takes 6-14 days depending on the daily dose selected 2
• Higher loading doses (up to 1200 mg daily) may be used in monitored inpatient settings, though this increases adverse effect risk 1

Atrial Fibrillation

• Use 600-800 mg per day in divided doses until a cumulative total of 10 grams is given 1
• After reaching 10 grams total, reduce to maintenance dose of 200 mg daily 1

Alternative Loading Approach

• A more conservative regimen of 400-600 mg daily in divided doses for 2-4 weeks can be used, followed by maintenance of 100-200 mg daily 1
• This approach may be preferred for less urgent situations or outpatient loading

Transitioning from IV to Oral Amiodarone

The oral dose depends on duration of prior IV therapy 1, 3:

• IV therapy <1 week: Start 800-1600 mg oral daily 1, 2
• IV therapy 1-3 weeks: Start 600-800 mg oral daily 1, 2
• IV therapy >3 weeks: Start 400 mg oral daily 1, 2

This accounts for the 50% bioavailability of oral amiodarone and ensures comparable total body drug delivery 3

Critical Monitoring During Loading

Cardiovascular Monitoring

• Watch for bradycardia, QT prolongation, hypotension, and heart block throughout the loading phase 1
• These effects can occur early despite the drug's long half-life 1

Dose Adjustment Strategy

• Reduce dose if side effects occur rather than discontinuing therapy when possible 1
• The frequency of adverse effects correlates directly with total amiodarone exposure (both dose and duration) 2
• Use the lowest effective dose to minimize toxicity 2

Long-term Toxicity Surveillance

• Monitor for pulmonary toxicity (cough, dyspnea, interstitial infiltrates), thyroid dysfunction, and hepatic toxicity during and after loading 1, 2
• Pulmonary toxicity is the most serious potential adverse effect 2

Important Clinical Considerations

Timing of Antiarrhythmic Effect

• Full antiarrhythmic effect may take days to weeks to develop despite adequate serum levels, due to amiodarone's very long half-life 1
• However, some electrophysiologic effects can be seen within 24-48 hours with high-dose loading 4

Drug Interactions

• Avoid coadministration with other QT-prolonging medications without expert consultation 1
• Reduce warfarin dose by one-third to one-half when starting amiodarone, as it increases prothrombin time by 100% after 3-4 days 3
• Reduce digoxin dose by approximately 50% or discontinue, as amiodarone increases serum digoxin by 70% after one day 3
• Avoid grapefruit juice, which increases amiodarone AUC by 50% and Cmax by 84% 3

Concomitant Antiarrhythmic Therapy

• When adding amiodarone to existing antiarrhythmic therapy, reduce the dose of the other agent by 30-50% several days after starting amiodarone 3
• For quinidine or procainamide specifically, reduce dose by one-third 3

Common Pitfalls to Avoid

• Do not use drop counter infusion sets if transitioning from IV, as surface properties can lead to 30% underdosing 3
• Do not exceed 2 mg/mL concentration for peripheral IV administration to avoid phlebitis 3
• Side effects are nearly universal (93% of patients in one study), so anticipate and manage them proactively rather than discontinuing therapy prematurely 5
• The narrow therapeutic window means careful dose titration is essential—the first sign of antiarrhythmic failure may be sudden cardiac death 5