Amiodarone Oral to Intravenous Equivalency
The recommended equivalency when converting from intravenous to oral amiodarone is based on a 50% bioavailability of oral amiodarone, meaning oral doses should be approximately twice the intravenous dose to achieve similar therapeutic effects. 1, 2
Conversion from IV to Oral Amiodarone
When transitioning from intravenous to oral amiodarone therapy, the following guidelines should be followed:
For patients receiving the standard IV maintenance infusion of 0.5 mg/min (720 mg/day), the recommended oral conversion doses are 1, 2:
- After <1 week of IV amiodarone: 800-1600 mg oral daily
- After 1-3 weeks of IV amiodarone: 600-800 mg oral daily
- After >3 weeks of IV amiodarone: 400 mg oral daily
Initial oral loading doses typically range from 800-1600 mg/day in divided doses until a total of 10g has been given, followed by maintenance doses of 200-400 mg/day 3
For outpatient initiation of oral amiodarone, 600-800 mg/day in divided doses is recommended until a total of 10g has been given, then 200-400 mg/day maintenance 3
Pharmacokinetic Considerations
The bioavailability of oral amiodarone is approximately 50%, which explains the need to double the dose when converting from IV to oral administration 1, 2
Intravenous amiodarone has a more rapid onset of action compared to oral administration, with antiarrhythmic effects occurring within 30 minutes of IV administration 3, 4
Oral amiodarone has a delayed onset of action due to its slow absorption and large volume of distribution, often requiring days to weeks to achieve full therapeutic effect 5
Clinical Applications
For life-threatening arrhythmias requiring immediate treatment, IV amiodarone is preferred with a recommended loading dose of 150 mg over 10 minutes (may be repeated in 10-30 minutes if necessary), followed by 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours 3, 6
For ventricular arrhythmias requiring oral therapy, initial doses of 800-1600 mg/day in divided doses are recommended until a total of 10g has been given, then 200-400 mg/day for maintenance 3
For atrial fibrillation, oral loading doses of 600-800 mg/day in divided doses until a total of 10g has been given, followed by maintenance doses of 200 mg/day are recommended 3
Monitoring and Safety Considerations
When transitioning between IV and oral formulations, close clinical monitoring is essential, particularly in elderly patients 1, 2
Common adverse effects of both formulations include hypotension, bradycardia, AV block, QT prolongation, and GI upset 3, 7
IV amiodarone at concentrations greater than 3 mg/mL has been associated with peripheral vein phlebitis; concentrations of 2.5 mg/mL or less are recommended for infusions longer than 1 hour 1
High-dose oral loading (800-2000 mg two to three times daily) has been shown to achieve rapid suppression of ventricular arrhythmias, with significant reductions in premature ventricular complexes beginning on the first day of therapy 5
Pitfalls and Caveats
Avoid grapefruit juice during oral amiodarone therapy as it inhibits CYP3A4-mediated metabolism, resulting in increased plasma levels 1, 2
IV amiodarone loading infusions at concentrations and rates higher than recommended have resulted in hepatocellular necrosis and acute renal failure 1
Amiodarone adsorbs to polyvinyl chloride (PVC) tubing, which can affect drug delivery; this was accounted for in clinical trials that established dosing recommendations 1, 2
Patients with preserved left ventricular function (ejection fraction >25%) are more likely to respond to IV amiodarone therapy 8