What are the adverse effects of Amiodarone (antiarrhythmic medication)?

Adverse Effects of Amiodarone

Amiodarone has numerous serious adverse effects affecting multiple organ systems, with pulmonary toxicity being the most concerning life-threatening complication, occurring in approximately 1-17% of patients depending on dosage. 1, 2

Major Adverse Effects by System

Pulmonary Toxicity

• Most serious adverse effect of amiodarone therapy 1
• Presentations include:
  • Subacute cough and progressive dyspnea (most common)
  • Interstitial infiltrates on chest radiographs
  • Reduced diffusing capacity on pulmonary function tests
  • Adult respiratory distress syndrome (less common, ~1% annually) 1
• Risk factors: Higher doses (>300 mg/day) and longer duration of treatment 1
• Management:
  • Immediate discontinuation of amiodarone
  • Supportive care
  • Corticosteroids in severe cases 2

Thyroid Dysfunction

• Occurs in approximately 2-10% of patients on long-term therapy 1, 3
• Manifestations:
  • Hypothyroidism (more common, 2-4× more frequent than hyperthyroidism) 1
  • Hyperthyroidism (from excess iodine or acute thyroiditis) 1
• Management:
  • For hypothyroidism: Continue amiodarone with thyroid hormone supplementation if clinically indicated 1, 2
  • For hyperthyroidism: Consider withdrawal of amiodarone, antithyroid medications, prednisone, or surgical thyroidectomy in refractory cases 1, 2

Hepatic Toxicity

• Elevated liver transaminases occur at a rate of 0.6% annually 1
• Affects 4-25% of patients 3
• Usually asymptomatic
• Discontinue amiodarone if liver enzyme levels exceed 3× normal unless patient is at high risk for life-threatening arrhythmia 1

Cardiovascular Effects

• Bradycardia and heart block: 1-3% of patients 1
• Hypotension with IV administration: 16% of patients 2, 4
• QT prolongation (common but rarely leads to torsades de pointes) 1, 2
• Proarrhythmia: <1% annually 1

Neurologic Toxicity

• Occurs in 20-40% of patients 3
• Manifestations:
  • Ataxia
  • Paresthesias
  • Tremor
  • Peripheral neuropathy (0.3% annually) 1
  • Sleep disturbances, dizziness, headaches 3
• Often dose-related and improves with dosage reduction 1

Dermatologic Effects

• Photosensitivity (common) 1
• Bluish skin discoloration in sun-exposed areas 1
• Allergic rash 3
• Rare but severe: Stevens-Johnson syndrome, toxic epidermal necrolysis 4

Ocular Effects

• Corneal microdeposits: Nearly all patients (visible on slit-lamp examination) 1
• Optic neuropathy/neuritis (rare but can progress to blindness) 1, 3

Gastrointestinal Effects

• Nausea, anorexia, constipation 1
• Usually dose-related and improve with dosage reduction 1

Other Adverse Effects

• Abnormal kidney function 4
• Hematologic: Thrombocytopenia, hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, agranulocytosis 4
• Psychiatric: Hallucinations, confusion, disorientation, delirium 4
• Endocrine: SIADH 4

Drug Interactions

• Warfarin: Increased anticoagulant effect 2
• Digoxin: Doubled serum levels 2
• Statins: Increased risk of myopathy/rhabdomyolysis 2
• Beta-blockers and calcium channel blockers: Potentiation of bradycardia 2

Monitoring Recommendations

• Baseline assessment:

  • Complete history and physical examination
  • Chest radiograph
  • Thyroid function tests
  • Liver transaminase levels
  • Pulmonary function tests
  • Ophthalmologic examination (if preexisting visual impairment) 2

• Regular monitoring (every 6 months):

  • Thyroid function tests (TSH, free T4, T3)
  • Liver transaminase levels
  • Directed history and physical examination 2
  • Pulmonary function tests and chest imaging as needed 2

Key Precautions

• Use lowest effective dose (often 200 mg/day) to minimize adverse effects 3
• Immediately assess any new or worsening dyspnea or cough for pulmonary toxicity 1
• Advise patients to use sunblock and cover exposed skin outdoors 1
• Adjust doses of interacting medications, particularly warfarin and digoxin 2
• Monitor for early signs of thyroid dysfunction 2

Amiodarone's adverse effects are often related to total drug exposure (dose and duration), highlighting the importance of using the lowest effective dose and appropriate monitoring to minimize complications while maintaining therapeutic efficacy.