What are the side effects of amiodarone?

Amiodarone Side Effects and Monitoring

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

• Pulmonary toxicity is the most serious potential adverse effect, presenting as subacute cough and progressive dyspnea with patchy interstitial infiltrates on chest radiographs 1
• Reduced diffusing capacity on pulmonary function tests is common in patients with pulmonary toxicity 1
• Any worsening dyspnea or cough requires 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 therapy 1
• Can cause both hyperthyroidism and hypothyroidism 1
• Regular monitoring of thyroid function tests is mandatory 1

Hepatic Effects

• Liver toxicity manifests as elevation of liver transaminase levels (0.6% annually) 1
• If liver enzyme levels exceed three times normal, amiodarone should be discontinued unless the patient is at high risk for life-threatening arrhythmia recurrence 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, 2
• Serious cardiovascular effects include asystole, cardiac arrest, electromechanical dissociation, and cardiogenic shock 2

Neurologic Effects

• Neurologic toxicity includes ataxia, paresthesias, and tremor (often dosage-related) 1
• Peripheral neuropathy occurs at a rate of 0.3% annually 1
• Other reported effects include hallucinations, confusion, disorientation, and delirium 2

Dermatologic Effects

• Photosensitivity is common; patients should use sunblock and cover exposed skin outdoors 1
• Severe reactions can include Stevens-Johnson syndrome, toxic epidermal necrolysis, and exfoliative dermatitis 2

Ocular Effects

• Corneal microdeposits are visible on slit-lamp examination in nearly all patients but rarely affect vision 1
• Optic neuropathy and optic neuritis have been reported in rare cases 1

Other Side Effects

• Gastrointestinal: Nausea, vomiting, diarrhea, and constipation 2
• Hematologic: Hemolytic anemia, aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, and agranulocytosis 2
• Musculoskeletal: Myopathy, muscle weakness, and rhabdomyolysis 2
• Reproductive: Epididymitis and impotence 2

Monitoring Recommendations

Baseline Assessment

• Complete history and physical examination 1
• Chest radiograph 1
• Thyroid studies 1
• Liver transaminase levels 1
• Pulmonary function tests 1

Regular Monitoring

• Thyroid studies and liver transaminase levels every six months 1
• History and physical examination directed at detecting adverse effects 1

Drug Interactions

• Amiodarone inhibits metabolism of several drugs through cytochrome P450 pathways 1
• Close monitoring of digoxin levels and prothrombin time is necessary when co-administered 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

Important 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, 3
• Due to high lipid solubility, amiodarone is stored in fat, muscle, liver, lungs, and skin 1
• Virtually all patients develop side effects at higher maintenance doses (600mg daily) 4
• Regular follow-up is essential as many toxic reactions develop only after prolonged therapy 5