What are the potential side effects of amiodarone?

Amiodarone Side Effects

Amiodarone has numerous serious side effects affecting multiple organ systems, with pulmonary toxicity being the most dangerous adverse effect occurring at a rate of approximately 1% annually, requiring immediate discontinuation if suspected. 1

Major Organ System Side Effects

Pulmonary Toxicity

• Most serious potential adverse effect
• Clinical presentation: subacute cough, progressive dyspnea, patchy interstitial infiltrates on chest radiographs, reduced diffusing capacity
• Less commonly presents as adult respiratory distress syndrome
• Incidence: 1% annually with doses ≤300mg/day
• Management: discontinuation of amiodarone, supportive care, sometimes corticosteroids
• Any report of worsening dyspnea or cough requires prompt evaluation 1

Cardiovascular Effects

• Bradycardia and heart block: 1-3% of patients
• Proarrhythmia: <1% annually
• QT prolongation common, but torsades de pointes rare
• IV administration: heart block/bradycardia (4.9%), hypotension (16%)
• Contraindicated in second/third-degree heart block without pacemaker 1, 2

Thyroid Dysfunction

• Occurs in 2-10% of patients on long-term therapy
• Hypothyroidism: 2-4 times more common than hyperthyroidism
• Hyperthyroidism may result from excess iodine or acute thyroiditis
• Management: thyroid hormone supplementation for hypothyroidism; antithyroid medications, prednisone, or surgical thyroidectomy for hyperthyroidism 1

Liver Toxicity

• Elevation of liver transaminases common
• Annual rate: 0.6%
• Rarely symptomatic
• Discontinue if liver enzymes >3 times normal unless high risk for life-threatening arrhythmia recurrence 1

Dermatologic Effects

• Photosensitivity: very common
• Blue-gray skin discoloration in sun-exposed areas after extended exposure
• Resolves slowly over months after discontinuation
• Management: sunblock and covering exposed skin when outdoors 1, 3

Ocular Effects

• Corneal microdeposits: visible on slit-lamp exam in nearly all patients, rarely affect vision
• Optic neuropathy/neuritis: rare but can progress to blindness
• Any changes in visual acuity or peripheral vision require ophthalmologic evaluation 1

Gastrointestinal Effects

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

Neurologic Effects

• Common effects include tremor and ataxia
• Other reported effects: hallucinations, confusion, disorientation, delirium 1, 2

Drug Interactions

• Potent inhibitor of multiple cytochrome P450 pathways:

  • CYP 2C9 (warfarin metabolism)
  • CYP 2D6 (beta blockers, narcotics)
  • CYP 3A4 (cyclosporine, calcium channel blockers)

• Most clinically important interactions:

  1. Warfarin: Reduces clearance, causing sudden increases in PT/INR

     • Peak effects occur ~7 weeks after initiation
     • Monitor PT/INR at least weekly for first 6 weeks

  2. Digoxin: Levels typically double due to inhibition of renal tubular secretion

     • Reduce digoxin dose by 50% when starting amiodarone
     • Monitor digoxin levels 1

Monitoring Recommendations

Baseline Assessment

• Complete history and physical exam (focus on heart failure, arrhythmias, medications)
• Chest radiograph
• Thyroid studies and liver transaminase levels
• Digoxin level, PT/INR (if applicable)
• Pulmonary function tests with DLCO
• Ophthalmologic exam (if preexisting visual impairment) 1

During Treatment

• Heart rate surveillance (especially during first week)
• Every 6 months:
  • Thyroid studies and liver transaminase levels
  • Digoxin level (if applicable)
  • History and physical exam for adverse effects
• For suspected pulmonary toxicity:
  • Chest radiograph
  • Pulmonary function tests
• For visual symptoms:
  • Ophthalmologic examination
• Regular skin examinations with attention to sun-exposed areas 1, 3

Clinical Pitfalls to Avoid

1. Failing to recognize pulmonary toxicity early - routine screening has limited value as toxicity can develop rapidly
2. Confusing amiodarone pneumonitis with congestive heart failure (must rule out early)
3. Not reducing warfarin and digoxin doses when starting amiodarone
4. Inadequate sun protection leading to photosensitivity reactions
5. Overlooking drug interactions with commonly used medications
6. Insufficient monitoring of thyroid and liver function
7. Using in patients with second/third-degree heart block without pacemaker 1, 2