What is the recommended intravenous amiodarone dosing protocol, indications, and monitoring for rapid rhythm control in unstable ventricular tachycardia, ventricular fibrillation, or acute atrial fibrillation with hemodynamic compromise?

Intravenous Amiodarone Infusion Protocol

Standard Loading and Maintenance Regimen

For life-threatening ventricular arrhythmias (VT/VF) or hemodynamically unstable rhythms, administer a 150 mg IV bolus over 10 minutes, followed by 1 mg/min for 6 hours, then 0.5 mg/min for the subsequent 18 hours, delivering approximately 1,050 mg in the first 24 hours. 1, 2

Cardiac Arrest Modification

• In pulseless VT/VF unresponsive to defibrillation and epinephrine, give 300 mg IV/IO bolus; if arrhythmia persists after defibrillation, administer an additional 150 mg bolus 1

Breakthrough Arrhythmia Dosing

• For recurrent VF or hemodynamically unstable VT during the maintenance infusion, repeat the 150 mg bolus over 10 minutes 1, 2

Primary Indications

Amiodarone IV is FDA-approved exclusively for initiation of treatment and prophylaxis of frequently recurring VF and hemodynamically unstable VT in patients refractory to other therapy. 3, 2

• Secondary prevention of life-threatening ventricular arrhythmias, particularly in patients with left ventricular dysfunction 3
• Adjunct therapy to reduce ICD shock frequency in patients with recurrent ventricular arrhythmias 3
• Emergency treatment of ventricular tachyarrhythmias requiring rapid antiarrhythmic effect 3

Atrial Fibrillation Considerations

• For AF with heart failure or accessory pathway, amiodarone is a Class IIa recommendation for rate control, though effect develops over days, not immediately 1
• Amiodarone is NOT first-line for rate control in hemodynamically stable AF without heart failure; β-blockers, diltiazem, or verapamil achieve rate control within 2–7 minutes 1
• Higher doses (>1,500 mg/day) are required for pharmacological cardioversion of recent-onset AF, with most conversions occurring 6–8 hours after initiation 4
• In one study, 450 mg IV bolus achieved sinus rhythm in 28% at 30 minutes and 42% at 60 minutes, superior to digoxin 5

Critical Cardiovascular Monitoring

Hypotension (Most Common Adverse Effect)

• Occurs in 16–26% of patients receiving IV amiodarone 1
• Management algorithm: Slow the infusion rate first; if hypotension persists, add vasopressor drugs, positive inotropic agents, or volume expansion as clinically indicated 1, 2

Bradycardia and Conduction Abnormalities

• Bradycardia and new AV block occur in approximately 4.9% of patients 1
• Slow or discontinue the infusion if heart rate falls below 50 bpm or if second- or third-degree AV block develops 1, 2

QT Interval Prolongation

• QT prolongation is common but rarely causes torsades de pointes with amiodarone compared to other antiarrhythmics 3, 1
• Obtain daily 12-lead ECGs and intervene if QTc exceeds 500 ms 1
• Always correct serum potassium and magnesium before and during therapy, as electrolyte deficiencies markedly increase proarrhythmic risk 1

Continuous Telemetry Requirements

• Maintain continuous cardiac monitoring for at least 24 hours after initiating IV amiodarone 1
• Perform daily 12-lead ECG to assess QT interval and detect heart block 6, 1

Mandatory Drug Interaction Adjustments

Digoxin

• Reduce digoxin dose by 50% immediately when starting IV amiodarone, as amiodarone approximately doubles digoxin serum levels 6, 3, 1

Warfarin

• Reduce warfarin dose by 30–50% and recheck INR within 3–5 days after initiating IV amiodarone, as amiodarone markedly increases anticoagulation 6, 3, 1
• Monitor INR weekly for the first 6 weeks 3

Statins

• Limit simvastatin to maximum 20 mg daily due to increased myopathy risk via CYP3A inhibition 3

Other CYP Interactions

• Amiodarone inhibits CYP1A2, CYP2C9, CYP2D6, and CYP3A, increasing exposure to numerous drugs metabolized by these pathways 2

Transition from IV to Oral Therapy

Timing Based on IV Duration

IV Duration	Oral Loading Dose	Cumulative Target	Maintenance
< 1 week	800–1,600 mg/day divided	10 g total (1–2 weeks)	200–400 mg/day
1–3 weeks	600–800 mg/day divided	10 g total	200–400 mg/day
> 3 weeks	400 mg/day	Already saturated	200–400 mg/day

6, 1

Overlap Strategy

• Begin oral amiodarone while continuing IV infusion at 0.5 mg/min; discontinue IV after 24 hours of oral dosing to ensure adequate tissue saturation given amiodarone's extremely long half-life (averaging 58 days, range 15–100 days) 6, 3, 1
• After completing the 10 g cumulative oral load, reduce to maintenance dose of 200–400 mg daily (some patients require as low as 100–200 mg daily) 6, 1

Expected Clinical Timeline

• The full antiarrhythmic effect takes days to weeks to develop despite therapeutic serum levels, due to slow tissue distribution 6, 1
• At 1 year after cardioversion, 62% of patients maintained sinus rhythm with amiodarone versus 23% with Class I antiarrhythmics 6, 1
• Median time to AF recurrence is 487 days with amiodarone versus 74 days with sotalol 6

Absolute Contraindications

Amiodarone is contraindicated in patients with: 2

• Known hypersensitivity to amiodarone or iodine
• Cardiogenic shock
• Marked sinus bradycardia
• Second- or third-degree AV block without a functioning pacemaker

Critical Pitfalls to Avoid

• Do NOT use IV calcium-channel blockers or digoxin in AF with pre-excitation syndrome (WPW); they may paradoxically accelerate ventricular response and precipitate VF 1
• Do NOT use IV calcium-channel blockers in decompensated heart failure with AF; they worsen hemodynamics 1
• Do not use amiodarone for primary prevention of sudden death; ICDs are more effective 3
• Avoid grapefruit juice, which inhibits amiodarone metabolism via CYP3A 3

Safety Profile in Structural Heart Disease

• Amiodarone can be safely used in patients with structural heart disease, including coronary artery disease and reduced ejection fraction, unlike Class IC agents (flecainide, propafenone) which are contraindicated 3, 4
• Amiodarone has neutral effects on mortality in heart failure patients, making it one of few antiarrhythmics safe in this population 3, 7
• Lower proarrhythmic risk compared to other antiarrhythmics in patients with structural heart disease 3

Long-Term Toxicity Considerations

• Long-term use causes serious multi-organ toxicity in up to 93% of patients, with 15–19% requiring discontinuation 3
• Mandatory monitoring includes thyroid function (baseline and every 6 months), liver function (baseline and every 6 months), baseline chest radiograph and pulmonary function tests, and regular ophthalmologic examinations 3
• Particularly problematic in older adults (≥75 years), classified as a potentially inappropriate medication (PIM) in this age group 3