What are the details about Amiodarone (antiarrhythmic medication)?

Amiodarone: A Comprehensive Overview

Amiodarone is a potent antiarrhythmic agent primarily indicated for life-threatening ventricular arrhythmias, with significant efficacy but requiring careful monitoring due to its complex pharmacokinetics and potential for serious adverse effects. 1

Pharmacology and Mechanism of Action

Amiodarone is a complex antiarrhythmic agent with properties spanning all four Vaughan Williams classifications:

• Class I: Blocks sodium channels at rapid pacing frequencies
• Class II: Exerts noncompetitive antisympathetic action
• Class III: Prolongs cardiac action potential (primary classification)
• Class IV: Produces negative chronotropic effects in nodal tissues 2

Key electrophysiologic effects include:

• Slowing heart rate and AV nodal conduction
• Prolonging refractoriness
• Slowing intracardiac conduction 2

Pharmacokinetics

Amiodarone has unusual pharmacokinetic properties:

• Variable and generally poor bioavailability (22-95%)
• Enhanced absorption when taken with food
• Highly lipid soluble with storage in fat, muscle, liver, lungs, and skin
• Extremely long half-life (average 58 days)
• Metabolized to desethylamiodarone (DEA), an active metabolite 1
• Eliminated primarily through hepatic metabolism and biliary excretion 2

Clinical Indications

FDA-Approved Indications

• Secondary prevention of life-threatening ventricular arrhythmias 1

Common Off-Label Uses

• Atrial fibrillation (more effective than sotalol or propafenone for maintaining sinus rhythm) 1, 3

Dosing Guidelines

Oral Administration

• Loading dose: 600 mg twice daily for 7 days
• Maintenance dose: Initially 400-600 mg daily, then reduced to lowest effective dose (often 200 mg/day) 4

Intravenous Administration

• Loading dose: 150 mg IV over 10 minutes (can be repeated in 10-30 minutes if necessary)
• Early maintenance: 1 mg/minute for 6 hours (360 mg)
• Later maintenance: 0.5 mg/minute for 18 hours (540 mg)
• Total loading dose: Approximately 1,000 mg for first 24 hours
• Subsequent maintenance: 0.5 mg/minute (720 mg/24 hours) 3

Monitoring and Safety

Baseline Assessment

• Complete history and physical examination
• Chest radiograph
• Thyroid function tests (TSH, free T4, T3)
• Liver transaminase levels
• Pulmonary function tests including diffusion capacity (DLCO)
• Ophthalmologic examination if preexisting visual impairment
• Digoxin level and prothrombin time/INR when appropriate 1

Ongoing Monitoring

• Every 6 months:

  • Thyroid function tests
  • Liver transaminase levels
  • Directed history and physical examination 1

• For suspected pulmonary toxicity:

  • Chest radiograph
  • Pulmonary function tests 1

• For visual symptoms:

  • Ophthalmologic examination 1

• During warfarin therapy:

  • Weekly monitoring of prothrombin time/INR for first 6 weeks 1

Major Adverse Effects

Pulmonary Toxicity (Most Serious)

• Incidence: 2-17% of patients 4
• Presentations:
  • Hypersensitivity pneumonitis (early onset)
  • Interstitial pneumonitis (insidious onset after months/years)
• Symptoms: Cough, dyspnea, low-grade fever, interstitial infiltrates 3
• Management: Discontinue amiodarone, provide supportive care, consider corticosteroids 3

Thyroid Dysfunction

• Hypothyroidism or hyperthyroidism (2-10% of patients) 4
• Management:
  • For hyperthyroidism: Consider antithyroid medications, prednisone, or amiodarone discontinuation
  • For hypothyroidism: Continue amiodarone and add levothyroxine 3

Cardiovascular Effects

• Bradycardia and heart block (1-3% of patients)
• QT prolongation (common but rarely causes torsades de pointes)
• Hypotension with IV administration (16% of patients) 1

Hepatic Effects

• Elevated liver enzymes (4-25% of patients) 4

Neurologic Effects

• Incidence: 20-40% of patients
• Manifestations: Tremor, ataxia, peripheral neuropathy, sleep disturbances 4

Dermatologic Effects

• Photosensitivity
• Blue-gray skin discoloration with chronic use 4

Gastrointestinal Effects

• Constipation (most common)
• GI upset 3

Drug Interactions

Major Interactions

• Warfarin: Increases anticoagulant effect; peak effect occurs at 7 weeks
• Digoxin: Doubles serum levels
• Statins: Increases risk of myopathy/rhabdomyolysis
• Beta-blockers and calcium channel blockers: Potentiates bradycardia
• Grapefruit juice: Can inhibit amiodarone metabolism 1, 3, 2

Contraindications

• Hypersensitivity to amiodarone or iodine
• Cardiogenic shock
• Marked sinus bradycardia
• Second- or third-degree AV block without a functional pacemaker
• Pregnancy and lactation 3

Practical Considerations

• Keep dosage at lowest effective level to minimize adverse effects
• Administer IV formulation through a central venous catheter when possible
• Avoid concentrations >3 mg/mL due to risk of phlebitis
• For patients with normal TSH and elevated free T4, continue monitoring without intervention (common biochemical effect) 1, 3

Key Pitfalls to Avoid

1. Failing to monitor thyroid and liver function regularly
2. Not adjusting warfarin dose when starting amiodarone
3. Overlooking early signs of pulmonary toxicity
4. Using high maintenance doses when lower doses may be effective
5. Not recognizing drug interactions, particularly with digoxin and warfarin 1, 4