What is the typical loading and maintenance dose regimen for Amiodarone (antiarrhythmic medication)?

Amiodarone Loading and Maintenance Dosing

For oral amiodarone loading, administer 400-600 mg daily in divided doses for 2-4 weeks, followed by maintenance dosing of 100-200 mg daily, though higher loading regimens of 800-1600 mg daily until 10 grams total are used for ventricular arrhythmias. 1

Oral Loading Regimens by Indication

Standard Loading Protocol

• Start with 400-600 mg daily in divided doses for 2-4 weeks for most arrhythmias, then transition to maintenance therapy of 100-200 mg daily 1
• This approach balances efficacy with tolerability and is appropriate for outpatient initiation in stable patients 2

Aggressive Loading for Ventricular Arrhythmias

• Administer 800-1600 mg per day in divided doses until a cumulative total of 10 grams is reached, then reduce to maintenance of 200-400 mg daily 1, 3
• This higher-intensity regimen achieves therapeutic effect more rapidly in life-threatening ventricular tachycardia or fibrillation 3

Atrial Fibrillation Loading

• Use 600-800 mg per day in divided doses until 10 grams total, then decrease to 200 mg daily maintenance 1
• In-hospital loading may be more appropriate when earlier rhythm restoration is needed, particularly in heart failure patients 2

Intravenous Loading Protocol

Initial 24-Hour Dosing

• Administer approximately 1000 mg over the first 24 hours using the following FDA-approved regimen 4:
  • Loading infusion: 150 mg over 10 minutes
  • Followed by 1 mg/min for 6 hours (360 mg)
  • Then 0.5 mg/min for remaining 18 hours (540 mg)

Maintenance IV Infusion

• Continue 0.5 mg/min (720 mg/24 hours) using concentrations of 1-6 mg/mL 4
• Concentrations >2 mg/mL require central venous catheter administration to prevent peripheral vein phlebitis 4
• Mean daily doses above 2100 mg increase hypotension risk 4

Breakthrough Arrhythmias

• Give 150 mg supplemental boluses in 100 mL D5W over 10 minutes for recurrent ventricular fibrillation or hemodynamically unstable ventricular tachycardia 4

Transitioning from IV to Oral Therapy

The oral dose depends on duration of prior IV therapy due to tissue drug accumulation 1:

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

Patients on IV therapy for 1-3 weeks have already accumulated significant tissue stores, making lower oral doses sufficient 1

Maintenance Dosing Strategy

Target Maintenance Range

• Reduce to 100-200 mg daily after loading is complete for most patients 1
• Higher maintenance doses of 200-400 mg daily may be needed for ventricular arrhythmias, but virtually all patients develop side effects at these levels 1

Dose Reduction Rationale

• The lowest effective dose minimizes toxicity while maintaining therapeutic benefit 5
• Side effects are dose-dependent and occur in 51-93% of patients on higher maintenance regimens 6, 7

Critical Monitoring Requirements

During Loading Phase

• Monitor PR interval (prolonged by amiodarone) 2
• Monitor QRS duration (widened by amiodarone) 2
• Monitor QT interval for excessive prolongation 2
• Watch for bradycardia (occurs in 4.9% with IV administration) 5
• Assess for hypotension (occurs in 16% with IV administration) 5

Long-Term Surveillance

• Check liver and thyroid function every 6 months during maintenance therapy 5
• Monitor for pulmonary toxicity presenting as cough, dyspnea, and interstitial infiltrates 3
• Assess for corneal microdeposits which occur in nearly all patients but are usually asymptomatic 7

Important Drug Interactions

Warfarin

• Reduce warfarin dose by one-third to one-half when starting amiodarone 5
• Monitor INR at least weekly for the first 6 weeks, as interaction effects peak at 7 weeks 5

Digoxin

• Reduce digoxin dose by 50% as amiodarone predictably doubles digoxin levels 5

QT-Prolonging Medications

• Avoid coadministration without expert consultation due to additive proarrhythmic risk 1

Administration Caveats

Route Considerations

• Use central venous catheter whenever possible for IV administration to prevent phlebitis 5
• Use in-line filter during IV administration 5
• Administer through volumetric infusion pump, not drop counters (which may underdose by 30%) 4

Contraindications

• Do not use in bradycardia or second/third-degree heart block without pacemaker 5
• Extreme caution required if heart rate <60 bpm without immediately life-threatening indication 5

Dietary Restriction

• Patients must avoid grapefruit and grapefruit juice as it inhibits CYP3A metabolism and increases plasma levels 5

Pharmacokinetic Considerations

• Half-life averages 58 days (range 15-100 days), creating significant overlap between IV and oral dosing 5
• Full antiarrhythmic effect may take days to weeks despite adequate serum levels 1
• Antiarrhythmic protection may persist up to 150 days after discontinuation 8