What is the recommended amiodarone dosing regimen for adults, including loading and maintenance doses, and how should it be modified for elderly patients or those with hepatic dysfunction?

Amiodarone Dosing

For intravenous amiodarone, administer a rapid loading dose of 150 mg over 10 minutes, followed by 1 mg/min for 6 hours, then 0.5 mg/min for 18 hours (total ~1000 mg in 24 hours); for oral therapy, load with 400–600 mg daily for 2–4 weeks, then reduce to 200–400 mg daily maintenance. 1, 2

Intravenous Dosing Protocol

Standard Loading Regimen

• Rapid bolus: Give 150 mg diluted in 100 mL of 5% dextrose in water (D5W) over 10 minutes for cardiac arrest, hemodynamically unstable ventricular tachycardia, or immediately life-threatening arrhythmias. 1, 2
• Early maintenance infusion: Continue at 1 mg/min for the next 6 hours (approximately 360 mg total). 1, 2
• Late maintenance infusion: Reduce to 0.5 mg/min for the subsequent 18 hours (approximately 540 mg total), delivering roughly 1000 mg in the first 24 hours. 1, 2
• Maximum daily dose: Do not exceed 2.2 g of amiodarone in any 24-hour period. 1, 2
• Maximum initial infusion rate: Do not exceed 30 mg/min. 1, 2

Alternative Loading for Stable Arrhythmias

• For hemodynamically stable atrial fibrillation or stable monomorphic ventricular tachycardia, administer 150 mg (or 5 mg/kg, approximately 300 mg) over 1 hour, followed by the same 1 mg/min → 0.5 mg/min maintenance schedule. 1

Breakthrough Arrhythmias

• If ventricular fibrillation or hemodynamically unstable ventricular tachycardia recurs, give a supplemental 150 mg bolus (diluted in 100 mL D5W) over 10 minutes; this may be repeated after 10–30 minutes if needed. 1, 2

Critical Administration Requirements

• Diluent: Use only 5% dextrose in water; normal saline causes drug precipitation. 1, 2
• Concentration limit: Keep infusion concentration ≤2 mg/mL unless a central venous catheter is used; concentrations >3 mg/mL cause high rates of peripheral vein phlebitis. 1, 2
• Delivery method: Use a volumetric infusion pump (not drop-counter devices, which can underdose by up to 30%) and place an in-line filter in the infusion line. 1, 2
• Vascular access: Administer through a central venous catheter whenever possible to minimize phlebitis risk. 1, 2

Duration of IV Therapy

• A maintenance infusion of up to 0.5 mg/min can be continued for 2–3 weeks regardless of age, renal function, or left ventricular function; experience beyond 3 weeks is limited. 2

Oral Dosing Protocol

Loading Phase

• Standard loading: Give 400–600 mg daily in divided doses for 2–4 weeks. 1, 3
• High-dose inpatient loading: In a monitored setting, doses up to 1200 mg daily may be used until arrhythmia suppression or apparent steady state is achieved (usually 2–4 weeks). 1, 4
• Alternative loading: Administer 600–800 mg daily until a total of 10 g is delivered. 3

Maintenance Phase

• Target maintenance dose: Reduce to 200–400 mg daily after the loading phase. 1, 3
• Minimum effective dose: Use 100–200 mg daily to minimize long-term adverse effects; doses ≤300 mg/day reduce pulmonary toxicity risk to approximately 1% annually. 1, 3
• Dose titration: Because 93% of patients develop side effects at 600 mg daily maintenance, lower doses (200–400 mg) should be standard. 5

Dosing Modifications for Special Populations

Elderly Patients

• Elderly patients (>65 years) show lower clearance (approximately 100 mL/hr/kg vs. 150 mL/hr/kg in younger patients) and increased terminal half-life (47 days vs. 20 days). 2
• Digoxin interaction in elderly: If the patient is on digoxin, use very low doses (0.0625 mg daily or every other day) and never exceed 0.125 mg daily in patients >70 years old with stage 4 chronic kidney disease receiving concurrent amiodarone. 6
• No specific amiodarone dose reduction is mandated by age alone, but close clinical monitoring is prudent. 2

Hepatic Dysfunction

• Standard dosing applies: Use the same loading and maintenance doses, but exercise extreme caution with close monitoring. 3
• Hepatic dysfunction is listed as a precaution rather than requiring specific dose reduction due to lack of pharmacokinetic data. 7, 3
• Monitoring threshold: Discontinue amiodarone if liver transaminases exceed three times the upper limit of normal, unless the drug is essential for managing life-threatening arrhythmias. 6, 3
• After a single IV dose in cirrhotic patients, significantly lower concentrations of the active metabolite (DEA) occur, but mean amiodarone levels are unchanged. 2

Renal Impairment

• Renal disease does not influence the pharmacokinetics of amiodarone or its active metabolite (DEA). 2
• No dose adjustment is required for renal dysfunction during chronic oral therapy. 2
• Acute kidney injury: Temporarily hold amiodarone during acute AKI episodes and reduce the dose by approximately 50% when restarting after renal function stabilizes. 6

Severe Left Ventricular Dysfunction

• Pharmacokinetics of amiodarone are not significantly altered, but the terminal elimination half-life of DEA is prolonged. 2
• Close clinical monitoring is prudent, but no specific dose adjustment is defined. 2

Critical Drug Interactions Requiring Dose Adjustment

Warfarin

• Reduce warfarin dose by 50% when starting amiodarone. 7, 1, 3
• Monitor PT/INR at least weekly during the first 6 weeks; peak interaction effects occur at approximately 7 weeks. 1, 6

Digoxin

• Reduce digoxin dose by 50% (or by 30–50%) when starting amiodarone, as digoxin levels typically double. 7, 1, 6
• Target a digoxin concentration of 0.5–0.9 ng/mL (lower than the traditional therapeutic window) while amiodarone is co-administered. 6
• Monitor digoxin levels every 6 months during maintenance therapy. 6

Simvastatin

• Limit simvastatin to 20 mg daily when used with amiodarone due to increased risk of myopathy. 6

Grapefruit Juice

• Patients must not consume grapefruit or grapefruit juice during amiodarone therapy, as it increases plasma levels by 50% (AUC) and 84% (Cmax). 1, 2

Monitoring Requirements

Baseline Assessment

• Obtain thyroid function tests (TSH), liver transaminases (AST/ALT), electrocardiogram (PR interval, QRS duration, QT interval), chest radiograph, pulmonary function tests with diffusion capacity (DLCO), and complete blood count. 6
• If the patient is on digoxin or warfarin, obtain baseline digoxin level and PT/INR. 6

During IV Administration

• Continuous ECG monitoring is mandatory for heart rate, AV conduction abnormalities, QT prolongation, PR interval, QRS duration, and blood pressure. 1
• Bradycardia occurs in approximately 4.9% and hypotension in 16–26% of patients receiving IV amiodarone. 1
• If bradycardia or heart block develops, discontinue the infusion or reduce the rate immediately. 1

During Oral Maintenance Therapy

• Monitor thyroid function tests (TSH) and liver transaminases every 6 months. 6, 3
• Monitor heart rate weekly initially; reduce doses of concomitant rate-control agents approximately 6 weeks after starting amiodarone. 1
• Reassess ECG after each dose change, measuring PR interval, QRS duration, and QT interval. 1
• If pulmonary symptoms (dyspnea, cough) develop, obtain chest radiograph and repeat pulmonary function tests immediately. 6, 3

Common Pitfalls and Caveats

• Delayed onset of action: The antiarrhythmic effect of IV amiodarone typically becomes apparent 20–30 minutes after administration, and most conversions to sinus rhythm occur after 6–8 hours, usually requiring ≥1 g total dose; this delayed onset makes amiodarone less appropriate as a first-line agent unless the patient is clinically stable. 1
• Electrolyte correction: Maintain serum potassium >4 mmol/L during amiodarone infusion to reduce pro-arrhythmic risk; hypokalemia substantially amplifies digoxin toxicity and arrhythmia risk. 1, 6
• Relative contraindications for IV use: Baseline heart rate <60 bpm, systolic blood pressure <100 mmHg, and moderate or severe left ventricular dysfunction are relative contraindications; use only if the arrhythmia is immediately life-threatening and no alternatives exist. 1
• Absolute contraindications: Second- or third-degree heart block without a pacemaker is an absolute contraindication. 1
• Pre-existing interstitial lung disease: Amiodarone should generally be avoided in patients with pre-existing ILD due to significant risk of worsening pulmonary toxicity. 3
• Long half-life implications: The average half-life is 58 days (range 15–100 days), creating significant overlap between IV and oral dosing and prolonged effects after discontinuation. 1, 6
• Toxicity is dose- and duration-dependent: Adverse effects occur in 81–93% of patients on maintenance doses of 200–600 mg/day, typically manifesting after weeks to months of therapy. 3