What are the potential adverse effects of Amiodarone?

Amiodarone Adverse Effects

Amiodarone has numerous potentially serious adverse effects affecting multiple organ systems, with pulmonary toxicity being the most serious complication occurring at a rate of approximately 1% annually. 1

Cardiovascular Adverse Effects

• Bradycardia and heart block: Occurs in 1-3% of patients on oral therapy 1
• Proarrhythmia: Less than 1% annually, despite QT prolongation 1
• Hypotension: Common with IV administration (16% of patients) 2
• Contraindications: Second or third-degree heart block without pacemaker 1

Pulmonary Toxicity

• Presentation: Subacute cough, progressive dyspnea, patchy interstitial infiltrates on chest radiographs, reduced diffusing capacity 1
• Incidence: 1% annually for severe cases (adult respiratory distress syndrome) 1
• Monitoring: Any new dyspnea or cough warrants immediate evaluation
• Management: Discontinuation of amiodarone, supportive care, sometimes corticosteroids 1

Thyroid Dysfunction

• Hypothyroidism: More common (2-4 times more frequent than hyperthyroidism) 1
• Hyperthyroidism: Can result from excess iodine or acute thyroiditis 1
• Management:
  • Hypothyroidism: May continue amiodarone with thyroid hormone supplementation
  • Hyperthyroidism: May require withdrawal of amiodarone, antithyroid medications, prednisone, or surgical thyroidectomy 1

Hepatic Toxicity

• Incidence: Elevated liver enzymes occur at a rate of 0.6% annually 1
• Presentation: Usually asymptomatic with elevated transaminases 1, 2
• Management: Discontinue if liver enzymes exceed three times normal (unless patient at high risk for life-threatening arrhythmia) 1

Dermatologic Adverse Effects

• Photosensitivity: Most common dermatologic effect 1, 3
• Blue-gray skin discoloration: Occurs in sun-exposed areas after extended exposure 1, 3
• Management: Sun protection with high-SPF sunblock and covering exposed skin 3
• Resolution: Skin discoloration resolves slowly over months after discontinuation 3

Ocular Adverse Effects

• Corneal microdeposits: Present in almost all patients on slit-lamp examination, rarely affect vision 1
• Optic neuropathy/neuritis: Rare but can progress to blindness 1
• Management: Ophthalmologic evaluation for any changes in visual acuity or peripheral vision 1

Gastrointestinal Adverse Effects

• Common symptoms: Nausea, anorexia, constipation 1
• Management: Usually dose-related and improve with dose reduction 1

Neurologic Toxicity

• Symptoms: Tremor, ataxia, peripheral neuropathy 1
• Other reported effects: Hallucination, confusional state, disorientation, delirium 2

Drug Interactions

• Warfarin: Reduces clearance, can cause sudden increases in INR 1
• Digoxin: Levels typically double due to inhibition of renal tubular secretion 1
• Other interactions: Affects metabolism of beta blockers, calcium channel blockers, cyclosporine 1

Monitoring Recommendations

• Baseline: Complete history and physical, chest radiograph, thyroid studies, liver enzymes, pulmonary function tests 1
• During loading: Close monitoring of heart rate, especially first week 1
• Every 6 months: Thyroid studies, liver enzymes, directed history and physical 1
• For suspected pulmonary toxicity: Chest radiograph, pulmonary function tests 1
• For visual symptoms: Ophthalmologic examination 1

Pitfalls and Caveats

1. Pulmonary toxicity can develop rapidly with no antecedent abnormalities on chest radiographs or pulmonary function tests 1
2. Congestive heart failure can mimic amiodarone pneumonitis and must be ruled out 1
3. Drug interactions are common and clinically significant, particularly with warfarin and digoxin 1
4. The elimination half-life is extremely long (averaging 58 days), leading to delayed onset of both therapeutic effects and toxicity 1
5. Side effects may persist for months after discontinuation due to tissue accumulation 1