Amiodarone

# Amiodarone ## Overview - **Classification**: Class III Antiarrhythmic agent - **Mechanism**: Primarily blocks potassium channels, prolonging repolarization and the refractory period. Also has alpha- and beta-blocking, and sodium/calcium channel-blocking properties. ## Primary Indications 1. **Life-threatening ventricular arrhythmias**: Recurrent ventricular fibrillation (VF) or hemodynamically unstable ventricular tachycardia (VT). 2. **Atrial Fibrillation (AF)**: Rate control and/or rhythm control (conversion and maintenance of sinus rhythm). 3. **ACLS**: Pulseless VF/VT refractory to defibrillation. ## Adult Dosing ### Standard Dosing **Pulseless Ventricular Fibrillation (VF) / Pulseless Ventricular Tachycardia (VT) (ACLS)** - **Dose**: **300 mg** - **Frequency**: Once. May repeat **150 mg** once for refractory VF/pulseless VT. - **Route**: Intravenous (IV) push - **Special Consideration**: Follow with continuous infusion if rhythm restored. **Ventricular Arrhythmias (Loading & Maintenance)** - **IV Loading (Acute)**: **150 mg** IV over **10 minutes** (15 mg/min). - **Route**: Intravenous infusion - **IV Maintenance**: **1 mg/min** for 6 hours, then **0.5 mg/min** for 18 hours or longer. - **Maximum**: **2.2 grams** in 24 hours (including loading doses). - **Route**: Intravenous infusion - **Oral Loading (Chronic)**: **800-1600 mg/day** in divided doses for **1-3 weeks**. - **Route**: Oral - **Oral Maintenance**: **200-400 mg/day** once daily or in divided doses. - **Route**: Oral - **Duration**: Chronic, long-term **Atrial Fibrillation (Off-label for acute cardioversion)** - **IV**: **150 mg** over **10 minutes**, then **1 mg/min** for 6 hours, then **0.5 mg/min**. - **Route**: Intravenous infusion ### Dose Adjustments - **Renal Impairment**: No specific dose adjustment needed. - **Hepatic Impairment**: Use with caution. Consider reduced dose in mild to moderate impairment. Contraindicated in severe hepatic dysfunction (oral formulation). - **Elderly Patients**: Start at the low end of the dosing range due to potential for decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose (IV Loading)**: **5 mg/kg** - **Frequency**: Administer over **30-60 minutes**. - **Dose (IV Maintenance)**: **5-15 mg/kg/day** - **Frequency**: Continuous IV infusion. - **Maximum**: **15 mg/kg/day** (or **1.2 g/day**, whichever is less). - **Special Notes**: Due to potential for benzyl alcohol toxicity (from IV vehicle), use caution. Oral dosing rarely used. ### Infants (1-12 months) - **Dose (IV Loading)**: **5 mg/kg** - **Frequency**: Administer over **20-60 minutes**. - **Dose (IV Maintenance)**: **5-15 mg/kg/day** - **Frequency**: Continuous IV infusion. - **Maximum**: **15 mg/kg/day** (or **1.2 g/day**, whichever is less). ### Children (1-12 years) - **Dose (IV Loading)**: **5 mg/kg** - **Frequency**: Administer over **20-60 minutes**. - **Dose (IV Maintenance)**: **5-15 mg/kg/day** - **Frequency**: Continuous IV infusion. - **Maximum**: **15 mg/kg/day** (or **1.2 g/day**, whichever is less). - **Oral Loading**: **10-15 mg/kg/day** - **Frequency**: In 1-2 divided doses for **4-14 days**. - **Oral Maintenance**: **5-10 mg/kg/day** - **Frequency**: Once daily. - **Maximum Oral**: **400 mg/day**. ### Adolescents (13-18 years) - **Dose**: Typically follows **adult dosing guidelines** for both IV and oral formulations. - **Maximum**: **Adult maximum doses** apply. ## Safety Information ### Contraindications - **Absolute**: Severe sinus bradycardia. - **Absolute**: Second- or third-degree atrioventricular (AV) block (unless a functional pacemaker is present). - **Absolute**: Cardiogenic shock. - **Absolute**: Hypersensitivity to amiodarone or iodine. - **Absolute**: Severe hepatic dysfunction (oral amiodarone). ### Common Adverse Effects - **Very Common (>10%)**: Corneal microdeposits, GI upset (nausea, vomiting, constipation, anorexia), photosensitivity, elevated liver enzymes. - **Common (1-10%)**: Thyroid dysfunction (hypo/hyperthyroidism), pulmonary toxicity (pneumonitis, fibrosis), tremor, neuropathy, blue-gray skin discoloration. - **Serious but Rare**: Pulmonary fibrosis, hepatotoxicity (fulminant), proarrhythmia (e.g., Torsades de Pointes), optic neuropathy. ### Key Drug Interactions - **Warfarin**: Markedly increases INR, bleeding risk. **Reduce warfarin dose by 30-50%**. - **Digoxin**: Increases digoxin levels, risk of toxicity. **Reduce digoxin dose by 50%**. - **Statins (Simvastatin, Lovastatin)**: Increased risk of myopathy/rhabdomyolysis. **Limit simvastatin to 20 mg/day, avoid lovastatin**. - **Beta-blockers/Calcium Channel Blockers (non-dihydropyridine)**: Increased risk of bradycardia, AV block, hypotension. Monitor closely. - **QT-prolonging drugs (e.g., TCAs, macrolides, fluoroquinolones)**: Increased risk of Torsades de Pointes. Avoid coadministration if possible. - **CYP450 Inhibitors/Inducers**: Amiodarone is metabolized by CYP3A4, 2C8; it inhibits CYP3A4, 2C9, 2D6, P-glycoprotein. Significant interactions. ## Monitoring & Follow-up - **Before Treatment**: Baseline ECG, chest X-ray (CXR), pulmonary function tests (PFTs) including diffusion capacity (DLCO), liver function tests (LFTs), thyroid function tests (TFTs), serum electrolytes (K+, Mg++). - **During Treatment**: - **LFTs**: Every 6 months. - **TFTs**: Every 6 months. - **ECG**: Periodically (e.g., every 6 months) to assess rhythm and QT interval. - **CXR**: Annually or if pulmonary symptoms develop. - **Ophthalmologic exam**: Annually for long-term therapy. - **Clinical Signs**: Monitor for cough, dyspnea, fatigue, weight loss (pulmonary toxicity); jaundice, dark urine (hepatic toxicity); visual disturbances (ocular toxicity); tremors, ataxia (neuropathy); changes in heart rate or rhythm. ## Clinical Pearls - 💡 **Long Half-Life**: Amiodarone has an extremely long half-life (up to 58 days), leading to prolonged effects and drug interactions even after discontinuation. - 💡 **Organ Toxicities**: Known for multi-organ toxicities (pulmonary, hepatic, thyroid, ocular, neurologic). Patient education is crucial for symptom recognition. - 💡 **Photosensitivity**: Advise patients to use sunscreen and wear protective clothing to prevent severe sunburn and blue-gray skin discoloration. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.