Overview
Amiodarone is a potent class III antiarrhythmic agent used for life-threatening ventricular arrhythmias refractory to other treatments. It has complex pharmacokinetics with a very long half-life, requiring careful loading and maintenance dosing. Due to its extensive side effect profile affecting multiple organ systems, it requires regular monitoring of pulmonary, hepatic, thyroid, and ocular function.
Mechanism of Action
Amiodarone primarily blocks potassium channels (class III antiarrhythmic), prolonging action potential duration and refractory period in cardiac tissues. It also exhibits non-competitive beta-adrenergic blockade, sodium channel blockade (class I effects), and weak calcium channel blockade (class IV effects), resulting in complex electrophysiological effects across multiple cardiac cell types.
Indications
- Life-threatening recurrent ventricular fibrillation
- Life-threatening recurrent hemodynamically unstable ventricular tachycardia
- Use only when patients have not responded to adequate doses of other antiarrhythmics or cannot tolerate alternative agents
Common Doses
- 200 mg tablets
- 400 mg tablets
- Typical maintenance dose: 400 mg daily
- Loading doses: 800-1600 mg daily in divided doses
Dosage
Individualize dosage based on arrhythmia severity and response. Start with loading dose of 800-1600 mg/day until therapeutic response (usually 1-3 weeks), then reduce to 600-800 mg/day for one month, then maintenance dose of 400 mg/day. Administer consistently with meals, using divided doses for ≥1000 mg/day or if GI intolerance occurs.
Black Box Warning
Black Box Warning: Pulmonary toxicity (including pulmonary fibrosis) can be fatal; monitor with chest x-ray and pulmonary function tests
Contraindications
- Cardiogenic shock
- Sick sinus syndrome
- Second- or third-degree AV block
- Bradycardia causing syncope without functioning pacemaker
- Known hypersensitivity to amiodarone or iodine
Side Effects
- Pulmonary toxicity (cough, dyspnea, pulmonary fibrosis)
- Hepatic injury (elevated liver enzymes, hepatitis, cirrhosis)
- Visual impairment (optic neuropathy, photophobia, corneal microdeposits)
- Thyroid abnormalities (hypothyroidism, hyperthyroidism)
- Bradycardia and conduction abnormalities
- Peripheral neuropathy
- Photosensitivity and blue-gray skin discoloration
- Gastrointestinal disturbances
- Neurologic effects (tremor, ataxia, peripheral neuropathy)
Interactions
- QT-prolonging drugs (increased risk of torsades de pointes)
- Warfarin (potentiates anticoagulant effect; reduce warfarin dose by 33-50%)
- Digoxin (increases digoxin levels; reduce digoxin dose by 50%)
- Beta-blockers, calcium channel blockers (potentiates bradycardia)
- Simvastatin, lovastatin (increased myopathy risk; limit doses)
- Cyclosporine (increased levels; monitor renal function)
- Phenytoin (increased levels; monitor concentrations)
- Grapefruit juice (increases amiodarone exposure)
- St. John's Wort (decreases amiodarone levels)
- Hepatitis C antivirals (sofosbuvir) - risk of symptomatic bradycardia
Counseling Points
- Take consistently with meals to improve absorption and reduce GI upset
- Use sun protection due to photosensitivity risk
- Report any new or worsening cough, shortness of breath, or chest pain immediately
- Notify all healthcare providers of amiodarone use due to numerous drug interactions
- Regular monitoring of lung, liver, thyroid, and eye function is essential
- Do not stop medication abruptly without medical supervision
- Carry medical alert identification indicating amiodarone use