Amiodarone Toxicity: Clinical Presentations and Management
Overview
Amiodarone toxicity affects multiple organ systems with pulmonary toxicity being the most serious and potentially life-threatening adverse effect, requiring immediate drug withdrawal and supportive care. 1, 2
The frequency of adverse effects is directly related to total drug exposure (dosage and duration), making dose minimization essential. 1
Pulmonary Toxicity (Most Serious)
Clinical Presentation
- Subacute cough and progressive dyspnea are the hallmark symptoms 1, 2
- Patchy interstitial infiltrates on chest radiograph 1
- Reduced diffusing capacity on pulmonary function tests 1
- Adult respiratory distress syndrome (ARDS) is a rare but severe presentation occurring at 1% annually 1
Key Diagnostic Considerations
- Pulmonary toxicity can develop rapidly with no antecedent abnormalities on baseline chest radiographs or pulmonary function tests, making routine screening of limited value 1
- Any patient report of worsening dyspnea or cough should prompt immediate assessment for pulmonary toxicity 1, 2
- Congestive heart failure can mimic amiodarone pneumonitis and must be ruled out early 1
- High-resolution CT scanning is helpful for diagnosis 1
Management
- Primary treatment is immediate withdrawal of amiodarone 1
- Provide supportive care 1
- Consider corticosteroids in some cases 1
- In most instances, toxicity is reversible 1
Incidence
Thyroid Dysfunction
Types and Relative Frequency
- Hypothyroidism is 2-4 times more common than hyperthyroidism 1, 2
- Hyperthyroidism results from excess iodine or acute thyroiditis 1
Management of Hypothyroidism
- Amiodarone may be continued with appropriate thyroid hormone supplementation if there is strong clinical indication 1, 2
Management of Hyperthyroidism
- Withdraw amiodarone if this can be done safely 1
- Add antithyroid medications or prednisone 1
- Consider surgical thyroidectomy 1
Hepatic Toxicity
Clinical Presentation
- Manifested by elevation of liver transaminase levels 1, 2
- Occurs at a rate of 0.6% annually in long-term therapy 1, 2
- Patients are rarely symptomatic 1
Management
- If liver enzyme levels are three times higher than normal, discontinue amiodarone unless the patient is at high risk for recurrence of life-threatening arrhythmia 1
- Monitor hepatic enzyme concentrations closely 3
Ocular Toxicity
Corneal Microdeposits
- Visible on slit-lamp examination in nearly all patients 1
- Seldom affect vision 1
- Rarely necessitate drug discontinuation 1
Optic Neuropathy/Neuritis
- Rare but serious complication 1
- Can progress to total blindness 1
- Any patient noting changes in visual acuity or peripheral vision should be referred for immediate ophthalmologic evaluation 1
Dermatologic Toxicity
Photosensitivity
- All patients should use sunblock and cover exposed skin when outdoors 2
- Bluish skin discoloration may develop in sun-exposed areas with extended exposure 2
Neurologic Toxicity
Clinical Manifestations
Gastrointestinal Toxicity
Common Symptoms
Management
Cardiovascular Toxicity (Overdose)
Acute Overdose Presentations
Management of Overdose
- Slow the infusion rate 3
- Use vasopressor drugs for hypotension 3
- Administer positive inotropic agents 3
- Provide volume expansion 3
- Temporary pacing for bradycardia and AV block 3
- Amiodarone is not dialyzable 3
Monitoring Recommendations
Baseline Assessment
- Complete history and physical examination 2
- Chest radiograph 2
- Thyroid function tests 2
- Liver function tests 2
- Pulmonary function tests 2
Regular Monitoring (Every 6 Months)
Critical Pitfall
- Drug interactions are common due to amiodarone's inhibition of multiple cytochrome P450 pathways (CYP1A2, CYP2C9, CYP2D6, CYP3A4) and p-glycoprotein 3
- Warfarin dose should be reduced by one-third to one-half with close prothrombin time monitoring 3
- Digoxin levels increase by 70% after one day; reduce dose by approximately 50% or discontinue 3