What are the top 5 side effects of amiodarone?

Top 5 Side Effects of Amiodarone

The top 5 side effects of amiodarone are pulmonary toxicity, thyroid dysfunction, liver toxicity, dermatologic effects (particularly photosensitivity), and neurologic toxicity, with pulmonary toxicity being the most serious adverse effect that can significantly impact morbidity and mortality.

1. Pulmonary Toxicity

• The most serious potential adverse effect of amiodarone therapy is pulmonary toxicity, which can be life-threatening 1
• Typically presents as subacute cough and progressive dyspnea with interstitial infiltrates on chest radiographs and reduced diffusing capacity 1
• Incidence ranges from 1-17%, with more recent studies showing lower rates (approximately 1% annually) in patients receiving ≤300 mg daily 1
• Requires immediate discontinuation of amiodarone, supportive care, and possibly corticosteroids 1
• Toxicity is usually reversible if detected early 1

2. Thyroid Dysfunction

• Both hypothyroidism (more common) and hyperthyroidism can occur due to amiodarone's high iodine content 1
• Hypothyroidism is 2-4 times more common than hyperthyroidism 1
• Occurs in approximately 6% (hypothyroidism) and 0.9-2% (hyperthyroidism) of patients 2
• Hypothyroid patients can continue amiodarone with thyroid hormone supplementation if clinically indicated 1
• Hyperthyroidism may require withdrawal of amiodarone, antithyroid medications, prednisone, or surgical thyroidectomy 1

3. Liver Toxicity

• Manifested primarily by elevation of liver transaminase levels 1
• Occurs at a rate of approximately 0.6% annually in patients on long-term therapy 1
• Patients are rarely symptomatic 1
• Amiodarone should be discontinued if liver enzyme levels exceed three times normal, unless the patient is at high risk for life-threatening arrhythmia recurrence 1
• Severe hepatotoxicity including hepatitis and cirrhosis occurs in <3% of patients 2

4. Dermatologic Effects

• Photosensitivity is extremely common, affecting 25-75% of patients 2
• All patients should use sunblock and cover exposed skin when outdoors 1
• Bluish skin discoloration may develop in exposed areas with extended sun exposure 1
• Skin discoloration typically resolves several months after discontinuation 1
• Younger patients (under 60 years) may be at higher risk for dermatologic side effects 3

5. Neurologic Toxicity

• Includes ataxia, paresthesias, tremor, and peripheral neuropathy 1
• Peripheral neuropathy occurs at a rate of 0.3% annually 1
• Most neurologic symptoms are dosage-related and improve with dose reduction 1
• Can significantly impact quality of life and may necessitate drug discontinuation in severe cases 4
• May be more common in elderly patients 5

Monitoring Recommendations

• Baseline assessment should include complete history and physical examination, chest radiograph, thyroid and liver function tests, and pulmonary function tests 1
• Regular monitoring every 6 months should include thyroid studies, liver function tests, and clinical assessment for adverse effects 1
• Any new symptoms of dyspnea or cough should prompt immediate evaluation for pulmonary toxicity 1
• Visual changes require prompt ophthalmologic evaluation 1
• Dose reduction can often mitigate side effects while maintaining therapeutic efficacy 1, 4

Important Considerations

• Amiodarone has an extremely long half-life (up to 2 months), which means adverse effects may persist long after discontinuation 5
• Drug interactions are common due to amiodarone's inhibition of multiple cytochrome P450 pathways 1
• Careful patient selection is crucial - amiodarone should be reserved for patients most likely to benefit given its significant side effect profile 2
• Lower maintenance doses (200-400mg daily) may reduce the incidence of adverse effects while maintaining efficacy 4