What are the side effects of Amiodarone?

Amiodarone Side Effects

Amiodarone causes adverse effects in virtually all patients, with pulmonary toxicity being the most serious and potentially life-threatening complication, occurring at approximately 1% annually in patients receiving ≤300 mg daily. 1, 2

Most Serious Adverse Effects

Pulmonary Toxicity (Most Critical)

• Pulmonary toxicity is the most dangerous complication and can be fatal, presenting as subacute cough and progressive dyspnea with patchy interstitial infiltrates on chest radiographs and reduced diffusing capacity on pulmonary function tests 1, 2
• Incidence ranges from 1-17% in early studies, but more recent data shows approximately 1% annually with dosages ≤300 mg daily 1, 2
• Adult respiratory distress syndrome can develop rapidly with no antecedent abnormalities on imaging or pulmonary function tests, making routine screening of limited value 1
• Any new dyspnea or cough requires immediate evaluation to rule out pulmonary toxicity versus congestive heart failure, which can mimic amiodarone pneumonitis 1
• Treatment requires withdrawal of amiodarone, supportive care, and corticosteroids in some cases; toxicity is reversible in most instances 1

Cardiovascular Effects

• Hypotension is the most common cardiovascular adverse effect leading to discontinuation (1.6% of patients) 3
• Bradycardia and heart block occur in 1-3% of patients 1
• Asystole/cardiac arrest/electromechanical dissociation occurs in 1.2% of patients 3
• Cardiogenic shock, congestive heart failure, and ventricular tachycardia are reported 3
• Amiodarone is contraindicated in patients with second- or third-degree heart block without a pacemaker 1
• Proarrhythmia occurs at <1% annually; torsades de pointes is rare despite universal QT prolongation 1

Organ System Toxicities

Thyroid Dysfunction

• Both hypothyroidism and hyperthyroidism occur due to amiodarone's high iodine content 2
• Hypothyroidism is 2-4 times more common than hyperthyroidism 1, 2
• Hyperthyroidism results from iodine excess or acute thyroiditis 1
• Hypothyroid patients can continue amiodarone with thyroid hormone supplementation if clinically indicated 1, 2
• Hyperthyroidism treatment includes amiodarone withdrawal (if safe), antithyroid medications, prednisone, or surgical thyroidectomy 1

Hepatotoxicity

• Liver toxicity manifests as elevated transaminases and occurs at 0.6% annually in long-term therapy 1, 2
• Patients are rarely symptomatic 1
• Discontinue amiodarone if liver enzymes exceed three times normal unless patient is at high risk for life-threatening arrhythmia recurrence 1
• Hepatotoxicity can occur with overdose 3

Ocular Effects

• Corneal microdeposits occur in nearly all patients on slit-lamp examination but seldom affect vision or require discontinuation 1
• Optic neuropathy and optic neuritis, sometimes progressing to total blindness, have been reported in small numbers of patients, though causality is not well established 1
• Any changes in visual acuity or peripheral vision require immediate ophthalmologic evaluation 1

Dermatologic Effects

• Photosensitivity is common; all patients must use sunblock and cover exposed skin outdoors 1, 2
• Bluish skin discoloration develops in exposed areas with extended sun exposure and resolves over several months after discontinuation 1, 2
• Postmarketing reports include injection site reactions: pain, erythema, edema, pigment changes, venous thrombosis, phlebitis, thrombophlebitis, cellulitis, necrosis, and skin sloughing 3
• Rare but serious: Stevens-Johnson syndrome, toxic epidermal necrolysis (sometimes fatal), erythema multiforme, and exfoliative dermatitis 3

Neurologic Toxicity

• Ataxia, paresthesias, and tremor are common and often dose-related, improving with dosage reduction 1, 2
• Peripheral neuropathy occurs at 0.3% annually 1, 2
• Other reported effects include hallucination, confusional state, disorientation, and delirium 3

Gastrointestinal Effects

• Nausea, anorexia, and constipation are common and dosage-related, usually improving with dose reduction 1
• Diarrhea and vomiting (sometimes fatal) have been reported 3

Additional Serious Adverse Effects

• Hematologic: hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, and agranulocytosis 3
• Respiratory: bronchiolitis obliterans organizing pneumonia (possibly fatal), respiratory distress, failure, and arrest 3
• Musculoskeletal: myopathy, muscle weakness, and rhabdomyolysis 3
• Other: SIADH, pseudotumor cerebri, vasculitis, thyroid nodules/cancer, and epididymitis 3

Critical Management Principles

Monitoring Requirements

• Baseline assessment must include complete history and physical examination, chest radiograph, thyroid function tests, liver function tests, and pulmonary function tests 2
• Monitor thyroid studies and liver function tests every 6 months with clinical assessment for adverse effects 2
• Immediate evaluation required for any new dyspnea or cough 2

Dosing Considerations

• Use the lowest possible maintenance dosage to minimize adverse effects 1
• Most adverse effects are related to total amiodarone exposure (dosage and duration) 1
• Overall, 9% of patients discontinue treatment due to adverse effects 3
• Side effects occur in approximately 93% of patients, though most are manageable 4

Drug Interactions

• Amiodarone inhibits multiple cytochrome P450 pathways, causing numerous drug interactions 2
• Specific interactions occur with warfarin, simvastatin, atorvastatin, and HIV antiretroviral medications 5