What is the recommended workup for amiodarone toxicity?

Recommended Workup for Amiodarone Toxicity

A comprehensive workup for amiodarone toxicity should include targeted assessment of pulmonary, thyroid, liver, cardiac, neurologic, dermatologic, and ocular systems, with baseline and periodic monitoring of organ function through specific laboratory and diagnostic tests. 1

Initial Assessment

• Complete history and physical examination with special attention to heart failure symptoms, arrhythmia patterns, and review of all concomitant medications 1
• Focused assessment for symptoms of organ toxicity including:
  • Pulmonary: New or worsening dyspnea, cough, or decreased exercise tolerance 1
  • Thyroid: Weight changes, heat/cold intolerance, palpitations, fatigue 1, 2
  • Liver: Right upper quadrant pain, jaundice, nausea 1
  • Neurologic: Tremor, ataxia, paresthesias 1, 3
  • Dermatologic: Photosensitivity, skin discoloration 1
  • Ocular: Changes in visual acuity or peripheral vision 1, 4

Laboratory and Diagnostic Testing

Baseline (Before Starting Amiodarone)

• Thyroid function tests (TSH, free T4) 1
• Liver function tests (ALT, AST, bilirubin) 1
• Complete blood count 5
• Renal function tests 5
• Chest radiograph 1
• Pulmonary function tests with diffusing capacity (DLCO) 1
• Electrocardiogram 5
• Ophthalmologic examination (especially if pre-existing visual impairment) 1
• Digoxin level (if taking digoxin) 1
• Prothrombin time/INR (if taking warfarin) 1

Monitoring Schedule

During Outpatient Loading

• Close heart rate surveillance, especially during first week 1
• Directed history and physical examination for adverse effects 1

Every 6 Months

• Thyroid function tests 1
• Liver function tests 1
• Directed history and physical examination for adverse effects 1
• Digoxin level (if applicable) 1

For Suspected Pulmonary Toxicity

• Chest radiograph 1
• Pulmonary function tests with DLCO 1
• Consider high-resolution CT scan of chest 1
• Rule out congestive heart failure (which can mimic amiodarone pneumonitis) 1

For Visual Symptoms

• Prompt ophthalmologic examination including fundoscopy and slit-lamp examination 1, 4

For Patients on Warfarin

• Monitor PT/INR at least once weekly during first 6 weeks of concomitant therapy 1
• Consider reducing warfarin dose by one-third to one-half 1, 4

For Patients on Digoxin

• Monitor digoxin levels closely 1
• Consider reducing digoxin dose by 50% when starting amiodarone 1, 4

System-Specific Monitoring for Toxicity

Pulmonary Toxicity (Most Serious)

• Monitor for subacute cough, progressive dyspnea 1
• Look for patchy interstitial infiltrates on chest radiographs 1
• Check for reduced diffusing capacity on pulmonary function tests 1
• Consider high-resolution CT scan for diagnosis 1
• Treatment: Withdraw amiodarone, provide supportive care, consider corticosteroids 1

Thyroid Dysfunction

• Monitor for both hypothyroidism (more common) and hyperthyroidism 1, 2
• For hypothyroidism: Consider thyroid hormone supplementation while continuing amiodarone if clinically indicated 1
• For hyperthyroidism: Consider withdrawing amiodarone if safe, adding antithyroid medications or prednisone, or surgical thyroidectomy in severe cases 1

Liver Toxicity

• Monitor for elevation of liver transaminases 1
• If liver enzyme levels exceed three times normal, consider discontinuing amiodarone unless patient is at high risk for life-threatening arrhythmia 1

Ocular Effects

• Monitor for corneal microdeposits (common but rarely affect vision) 1
• Watch for optic neuropathy/neuritis (rare but can progress to blindness) 1, 4
• Refer for ophthalmologic evaluation if visual changes occur 1, 4

Dermatologic Effects

• Advise patients to use sunblock and cover exposed skin outdoors 1
• Monitor for bluish skin discoloration in sun-exposed areas 1

Neurologic Toxicity

• Monitor for tremor, ataxia, paresthesias (often dose-related) 1, 3
• Watch for peripheral neuropathy (occurs at rate of 0.3% annually) 1

Cardiovascular Effects

• Monitor for bradycardia and heart block (1-3% of patients) 1
• Watch for QT prolongation (common) but torsades de pointes (rare) 1

Common Pitfalls and Caveats

• Failure to obtain baseline tests before initiating therapy 6, 5
• Inadequate monitoring of thyroid and liver function (most commonly missed) 6, 5
• Not adjusting doses of interacting medications (especially warfarin and digoxin) 1, 4
• Overlooking early signs of pulmonary toxicity 1, 7
• Failing to recognize that toxicity can occur with both oral and intravenous formulations 4, 7
• Not considering that toxicity can occur rapidly with IV administration or may develop after years of oral therapy 4, 7
• Overlooking that amiodarone has an extremely long half-life, so toxicity may persist or appear even after drug discontinuation 4, 3