What are the effects of taking too much amiodarone (antiarrhythmic medication)?

Effects of Amiodarone Overdose

Excessive amiodarone intake causes life-threatening pulmonary toxicity, cardiovascular collapse with hypotension and bradycardia, hepatotoxicity, and multi-organ dysfunction that can be fatal even with aggressive treatment. 1, 2

Acute Overdose Effects (Immediate Concerns)

Cardiovascular Collapse

• Hypotension and cardiogenic shock are the primary acute manifestations requiring immediate intervention 1
• Severe bradycardia and AV block develop rapidly and may necessitate temporary cardiac pacing 1
• Treatment requires slowing infusion rate (if IV), vasopressor drugs, positive inotropic agents, and volume expansion 1

Hepatotoxicity

• Acute hepatic injury occurs with overdose, requiring close monitoring of hepatic enzyme concentrations 1
• Liver transaminase elevations can be severe and symptomatic in overdose scenarios 3

Chronic Excessive Dosing Effects (Most Dangerous)

Pulmonary Toxicity - The Most Serious Threat

• Pulmonary toxicity is the most serious and potentially fatal adverse effect of excessive amiodarone exposure 3, 4
• Presents as subacute cough and progressive dyspnea with patchy interstitial infiltrates on chest radiographs and reduced diffusing capacity 3, 4
• Fatal pulmonary toxicity can occur even with early corticosteroid treatment - one documented case involved 32.2g administered over 30 days (instead of planned 15.6g), resulting in death from respiratory failure due to bipulmonal pneumonitis despite aggressive intervention 2
• Adult respiratory distress syndrome occurs at 1% annually with therapeutic dosing, but risk increases dramatically with overdosing 3
• Pulmonary toxicity can develop rapidly without antecedent abnormalities on screening tests, making prevention through dose control critical 3
• Treatment involves immediate withdrawal, supportive care, and corticosteroids, though toxicity may be irreversible 3

Thyroid Dysfunction

• Both hyperthyroidism and hypothyroidism occur in 2-24% of patients on long-term therapy, with risk increasing with higher cumulative doses 3, 4
• Hypothyroidism is 2-4 times more common than hyperthyroidism 3
• Results from excess iodine content or acute thyroiditis 3

Hepatic Toxicity

• Liver toxicity with transaminase elevation occurs at 0.6% annually with therapeutic dosing 3
• If liver enzymes exceed 3 times normal, amiodarone must be discontinued unless patient faces life-threatening arrhythmia recurrence 3

Neurological Toxicity

• Ataxia, paresthesias, tremor, and peripheral neuropathy are dose-related and worsen with excessive exposure 3, 4
• Peripheral neuropathy occurs at 0.3% annually with therapeutic dosing 3, 4
• Neurologic side effects occurred in 52 of 70 patients (74%) in one series, predominantly tremor and ataxia 5

Cardiovascular Proarrhythmia

• Bradycardia and heart block occur in 1-3% of patients 3, 4
• QT prolongation is universal, though torsades de pointes remains rare even with overdose 3
• Amiodarone is contraindicated in second- or third-degree heart block without pacemaker 3, 4

Ocular Toxicity

• Corneal microdeposits occur in nearly all patients and are dose-related 3, 4
• Optic neuropathy and optic neuritis can progress to total blindness in rare cases 3

Dermatologic Effects

• Photosensitivity is common and worsens with higher doses 3, 4
• Bluish skin discoloration develops in sun-exposed areas with prolonged excessive exposure 3

Gastrointestinal Effects

• Nausea, anorexia, and constipation are dose-related and improve with dose reduction 3
• Gastrointestinal side effects occurred in 56 of 70 patients (80%) in one series 5

Critical Clinical Considerations

Why Overdose is Particularly Dangerous

• Amiodarone has an extremely long half-life (average 58 days), meaning adverse effects persist long after discontinuation 4
• High lipid solubility causes accumulation in fat, muscle, liver, lungs, and skin 4
• Amiodarone is not dialyzable, limiting treatment options for overdose 1

Mortality Risk

• Overall mortality in one series was 12.6% (12 of 95 patients), with 2 sudden deaths and 10 from heart failure 6
• 19% of patients required discontinuation due to severe side effects in another series 5
• Side effects occurred in 93% of patients in one study, with virtually all patients developing adverse effects when given 600mg daily maintenance 5, 7

Dose-Response Relationship

• Frequency of most adverse effects is directly related to total amiodarone exposure (dosage × duration) 3
• Studies show lower incidence of pulmonary toxicity with dosages ≤300mg/day compared to higher doses 3
• The lowest possible effective dosage must be used to minimize life-threatening toxicity 3, 4