What is the dosing regimen for Amiodarone?

Amiodarone Dosing Regimen

For oral loading, administer 600-800 mg daily in divided doses until a total of 10 grams is reached (typically 1-2 weeks), then reduce to a maintenance dose of 200 mg daily. 1

Oral Loading Dose Protocol

Standard Loading Regimen

• Start with 600-800 mg daily in divided doses (2-3 times per day) and continue until a cumulative total of 10 grams has been administered 1, 2
• This loading phase typically takes 1-2 weeks depending on the daily dose used 3
• For ventricular arrhythmias specifically, higher loading doses of 800-1600 mg daily may be used until the 10-gram total is reached 2, 3
• Alternative loading: 400-600 mg daily in divided doses for 2-4 weeks is also acceptable, though this represents a more conservative approach 2

High-Dose Loading (Inpatient Setting)

• For unstable patients requiring rapid loading, doses up to 1200 mg daily may be considered, but only with continuous monitoring in an inpatient setting 2
• High-dose protocols (50 mg/kg/day for 3 days, then 30 mg/kg/day for 2 days) have been studied but carry increased risk of adverse effects and should be reserved for refractory cases 4

Maintenance Dosing

Standard Maintenance

• After completing the 10-gram loading dose, reduce to 200 mg daily 1, 3
• Some patients may require 200-400 mg daily for adequate arrhythmia suppression 2, 5
• The dose should be kept at the lowest effective level to minimize toxicity, as virtually all patients develop side effects at higher maintenance doses 6

Dose Adjustment Strategy

• Monitor clinical response and adjust downward if side effects occur 2
• In clinical practice, maintenance doses often need to be reduced from initial levels (e.g., from 572 mg/day at 45 days to 372 mg/day at 6 months) due to adverse effects 6

Intravenous Dosing

IV Loading Protocol

• Loading dose: 150 mg over 10 minutes, followed by 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours 1, 7
• Total first 24-hour dose is approximately 1000 mg 7
• For breakthrough ventricular fibrillation or hemodynamically unstable ventricular tachycardia, administer supplemental 150 mg infusions over 10 minutes 7

IV Maintenance

• Continue 0.5 mg/min (720 mg/24 hours) maintenance infusion 7
• Can be cautiously continued for 2-3 weeks regardless of age, renal function, or left ventricular function 7
• Maintenance infusion rate may be increased to achieve effective arrhythmia suppression, but mean daily doses above 2100 mg are associated with increased risk of hypotension 7

Transitioning from IV to Oral

Duration-Based Conversion

• If IV amiodarone given for <1 week: start oral dosing at 800-1600 mg daily 2, 3
• If IV amiodarone given for 1-3 weeks: start oral dosing at 600-800 mg daily 2, 3
• If IV amiodarone given for >3 weeks: start oral dosing at 400 mg daily 2

Transition Strategy

• Begin oral amiodarone while IV infusion is still running due to the drug's extremely long half-life (15-100 days, average 58 days) 3, 8
• Continue oral loading until the 10-gram total is reached, then transition to maintenance dosing of 200-400 mg daily 3

Critical Monitoring Requirements

During Loading Phase

• Monitor for bradycardia (occurs in 1-3% on oral therapy, 4.9% on IV), hypotension (16% with IV), QT prolongation, and AV block 2, 3, 8
• Check ECG daily to assess QT interval and detect heart block 3
• Continuous telemetry monitoring for at least 24 hours after IV discontinuation 3
• Monitor heart rate every 4-6 hours initially, then at least daily 3

Electrolyte Management

• Verify normal potassium and magnesium levels before and during therapy, as deficiencies increase proarrhythmic risk 3

Important Drug Interactions

Warfarin

• Reduce warfarin dose by 30-50% when starting amiodarone and check INR within 3-5 days 3, 8
• Monitor INR at least weekly for the first 6 weeks, as interaction effects don't peak until 7 weeks 8

Digoxin

• Reduce digoxin dose by 50% immediately when starting amiodarone, as amiodarone doubles digoxin levels 3, 8

Other Rate-Control Medications

• Reduce doses of beta-blockers and calcium channel blockers as amiodarone's rate-control effect develops 3

Administration Considerations

IV Administration Specifics

• Administer through a central venous catheter whenever possible 8, 7
• Use concentrations ≤2 mg/mL for peripheral administration to minimize phlebitis risk 7
• Concentrations >2 mg/mL require central venous access 7
• Use an in-line filter during administration 8, 7
• Must be delivered by volumetric infusion pump, not drop counter sets, as drop size reduction can lead to 30% underdosing 7
• Administer in glass or polyolefin bottles with D5W for infusions >2 hours 7

Contraindications

• IV amiodarone is contraindicated in patients with bradycardia or second/third-degree heart block without a pacemaker 8
• Use with extreme caution if baseline heart rate <60 bpm unless the arrhythmia is immediately life-threatening 8

Common Pitfalls

Adverse Effects

• 93% of patients develop side effects, with 19% requiring discontinuation 6
• Most common: gastrointestinal effects (especially constipation), corneal microdeposits (nearly universal), tremor/ataxia, photosensitivity 6, 5
• Serious toxicities: pulmonary toxicity (5%), thyroid dysfunction (6%), hepatotoxicity 6, 5
• Monitor liver and thyroid function every 6 months during maintenance therapy 8

Delayed Onset of Action

• Despite adequate serum levels, full antiarrhythmic effect may take days to weeks to develop due to the drug's pharmacokinetics 2, 3
• This delayed effect necessitates the prolonged loading phase and explains why breakthrough arrhythmias may occur early in therapy 3