Side Effects of Amiodarone
Amiodarone has numerous serious side effects affecting multiple organ systems, with pulmonary toxicity, thyroid dysfunction, liver abnormalities, and cardiovascular effects being the most concerning for morbidity and mortality. 1, 2
Major Organ System Side Effects
Cardiovascular Effects
- Bradycardia and heart block: Occurs in 1-3% of oral therapy patients 1
- Proarrhythmia: Less than 1% annually 1
- QT interval prolongation: Almost universal but rarely causes torsades de pointes 1
- With IV administration: 2
- Hypotension (16%)
- Heart block or bradycardia (4.9%)
- Cardiogenic shock
Pulmonary Toxicity
- Interstitial pneumonitis (potentially fatal) 2
- Pulmonary fibrosis 3
- Bronchiolitis obliterans organizing pneumonia 2
- Respiratory symptoms: Dyspnea, cough, hemoptysis, wheezing 2
Thyroid Dysfunction
- Both hypothyroidism and hyperthyroidism can occur 1, 2
- Requires regular monitoring every 6 months 1
- Thyroid nodules/thyroid cancer have been reported 2
Hepatic Effects
- Liver function test abnormalities 2
- Hepatotoxicity ranging from mild transaminitis to severe hepatitis 2, 3
- Requires monitoring of liver enzymes every 6 months 1
Dermatologic Effects
- Photosensitivity: Most common dermatologic effect 4
- Blue-gray skin discoloration in sun-exposed areas (face, neck, hands) 4
- Severe reactions: Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme 2
- Skin cancer has been reported 2
Neurological Effects
- Tremor and ataxia: Very common 5
- Peripheral neuropathy 2
- Neuropsychiatric: Hallucinations, confusion, disorientation, delirium 2
Ocular Effects
- Corneal microdeposits: Nearly universal with prolonged use 5
- Visual symptoms: Halos around lights, photophobia 1
Drug Interactions
Amiodarone is a potent inhibitor of multiple cytochrome P450 pathways, leading to significant drug interactions: 1
- Warfarin: Reduces clearance, causing sudden increases in INR; peak effects occur around 7 weeks after initiation 1
- Digoxin: Levels typically double due to inhibition of renal tubular secretion 1
- Statins: Increased risk of myopathy and rhabdomyolysis 3, 6
- Other antiarrhythmics: Increased risk of QT prolongation 6
- HIV medications: Multiple interactions 3
Monitoring Recommendations
Regular monitoring is essential to detect toxicity early: 1
- Baseline: Complete history and physical exam, chest X-ray, thyroid studies, liver enzymes, pulmonary function tests
- Every 6 months: Thyroid studies, liver enzymes
- For specific symptoms:
- Pulmonary: Chest X-ray and pulmonary function tests if respiratory symptoms develop
- Visual: Ophthalmologic exam if visual symptoms occur
- Warfarin therapy: Weekly INR monitoring for first 6 weeks
Important Caveats
- Side effects are extremely common, occurring in up to 93% of patients on higher doses 5
- Many side effects are dose-dependent; using the lowest effective dose is critical 7
- Blue-gray skin discoloration resolves slowly over months after discontinuation 4
- Sun protection is essential for all patients on amiodarone (high-SPF sunblock, covering exposed skin) 4
- Amiodarone has an extremely long half-life, meaning side effects may persist for months after discontinuation 7
Contraindications
- Second or third-degree heart block without a pacemaker 1
- Bradycardia without pacemaker 1
- Severe respiratory failure 6
- Hepatocellular failure 6
- Hyperthyroidism 6
Despite its numerous side effects, amiodarone remains an important antiarrhythmic medication when properly monitored and when the benefits outweigh the risks.