Side Effects of Amiodarone
Amiodarone has numerous potentially harmful side effects affecting multiple organ systems, with pulmonary toxicity being the most serious adverse effect requiring regular monitoring and prompt intervention. 1
Major Organ System Effects
Pulmonary Toxicity
- Most serious potential adverse effect of amiodarone therapy 1
- Presents as subacute cough and progressive dyspnea with patchy interstitial infiltrates on chest radiographs 1
- Reduced diffusing capacity on pulmonary function tests 1
- Any report of worsening dyspnea or cough should prompt immediate assessment 1
- Treatment involves withdrawal of amiodarone, supportive care, and sometimes corticosteroids 1
Thyroid Dysfunction
- Occurs in 2-24% of patients receiving long-term amiodarone therapy 1
- Can cause both hyperthyroidism (from excess iodine or acute thyroiditis) and hypothyroidism (2-4 times more common than hyperthyroidism) 1, 2
- Regular monitoring of thyroid function tests is mandatory 1
- In hypothyroid patients with strong indication for amiodarone, the drug may be continued with thyroid hormone supplementation 1
Liver Toxicity
- Manifested by elevation of liver transaminase levels 1
- Occurs at a rate of 0.6% annually 1
- Patients are rarely symptomatic 1
- If liver enzyme levels exceed three times normal, amiodarone should be discontinued unless patient is at high risk for recurrence of life-threatening arrhythmia 1
Cardiovascular Adverse Effects
- Bradycardia and heart block occur in 1-3% of patients 1
- Amiodarone-induced proarrhythmia occurs at an annual rate of <1% 1
- QT interval prolongation is common, but torsades de pointes is rare 1
- Contraindicated in patients with second- or third-degree heart block without a pacemaker 1
- IV administration can cause hypotension (16% of patients) 1
Other Common Side Effects
Neurologic Toxicity
- Includes ataxia, paresthesias, and tremor 1
- Often dosage-related and improve with dose reduction 1
- Peripheral neuropathy occurs at a rate of 0.3% annually 1
Dermatologic Adverse Effects
- Photosensitivity is common - patients should use sunblock and cover exposed skin outdoors 1
- Bluish skin discoloration may develop in areas with extended sun exposure 1
- Resolves over several months after discontinuation 1
Ocular Adverse Effects
- Corneal microdeposits visible on slit-lamp examination in nearly all patients 1
- Rarely affect vision or require discontinuation 1
- Optic neuropathy and optic neuritis have been reported in rare cases 1
- Any changes in visual acuity or peripheral vision warrant ophthalmologic evaluation 1
Gastrointestinal Adverse Effects
Monitoring Recommendations
Baseline Assessment
- Complete history and physical examination 1
- Chest radiograph 1
- Thyroid studies and liver transaminase levels 1
- Digoxin level, prothrombin time, and INR when appropriate 1
- Pulmonary function tests, including diffusing capacity 1
Regular Monitoring
- Every six months: thyroid studies and liver transaminase levels 1
- Digoxin level as appropriate 1
- History and physical examination directed at detecting adverse effects 1
- For suspected pulmonary toxicity: chest radiograph and pulmonary function tests 1
- For visual symptoms: ophthalmologic examination 1
Drug Interactions
- Amiodarone inhibits metabolism of several drugs through cytochrome P450 pathways 1
- Close monitoring of digoxin levels and prothrombin time in patients taking these medications 1
- Effects of interaction with warfarin and digoxin peak seven weeks after initiation 1
- Grapefruit juice can inhibit amiodarone metabolism and lead to elevated drug levels 1
Practical Considerations
- Keep amiodarone dosage at the lowest effective level to minimize side effects 1
- The long half-life (average 58 days) means adverse effects may persist after discontinuation 1
- Due to high lipid solubility, amiodarone is stored in fat, muscle, liver, lungs, and skin 1
- Almost all patients develop some side effects at maintenance doses of 600 mg daily 3