CORDARONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CORDARONE (CORDARONE).

How it works

Class III antiarrhythmic agent; prolongs action potential duration and refractory period via blockade of potassium channels; also exhibits class I, II, and IV properties including sodium channel blockade, non-competitive beta-adrenergic blockade, and calcium channel blockade.

What the body does with it

Metabolism	Hepatic, primarily via CYP3A4 and CYP2C8; major metabolite is N-desethylamiodarone; also inhibits CYP1A2, CYP2C9, CYP2D6, CYP3A4, P-glycoprotein.
Excretion	Primarily hepatic metabolism with biliary excretion; minimal renal elimination (<1% unchanged). Fecal excretion accounts for ~70% of the dose. Less than 10% excreted in urine.
Half-life	Terminal half-life ranges 40–70 days (mean 55 days) due to extensive tissue accumulation, particularly in adipose tissue. Prolonged half-life necessitates loading doses and long washout periods.
Protein binding	99.7% bound, primarily to albumin and β-lipoproteins.
Volume of Distribution	Very large: 20–200 L/kg (mean 130 L/kg), reflecting extensive tissue distribution and accumulation in adipose, liver, lung, and myocardium.
Bioavailability	Oral: 20–55% (mean ~40%) due to variable absorption and first-pass metabolism. IV: 100%.
Onset of Action	IV: Within 2–3 hours for arrhythmia control. Oral: Days to weeks (2–7 days) due to slow accumulation; full antiarrhythmic effect may take 1–3 months.
Duration of Action	After discontinuation, antiarrhythmic effect persists for weeks to months due to extensive tissue stores (e.g., 4–6 months). Clinical monitoring required after cessation.

Classification & Brands

Action Class	Class III Agents- anti arrhythmic
Brand Substitutes	Amiojust 100mg Tablet, Amiodon 100mg Tablet, Amione 100mg Tablet, Eurythmic 100mg Tablet, Panarol 100mg Tablet, Duron 150mg Injection, Amiodon 150mg Injection, Eurythmic 150mg Injection, Cardasol 150mg Injection, Tachyra 150mg Injection

Dosing & administration

Loading dose: 800-1600 mg/day orally in divided doses for 1-3 weeks, then 600-800 mg/day for 1 month, then maintenance: 200-400 mg/day. IV: Loading 150 mg over 10 minutes, then 1 mg/min for 6 hours, then 0.5 mg/min.

Dosage form	TABLET
Renal impairment	No adjustment required for GFR >10 mL/min. For GFR <10 mL/min, consider reducing maintenance dose by 25% due to accumulation of active metabolite.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce loading dose by 25-50% and maintenance by 25%. Child-Pugh C: Avoid use due to risk of toxicity.
Pediatric use	Loading: 10-20 mg/kg/day orally in 2 divided doses for 7-10 days, then 5-10 mg/kg/day for 5-7 days, then maintenance 2.5-5 mg/kg/day. IV: 5 mg/kg over 30 minutes, then 10-15 mg/kg/day continuous infusion.
Geriatric use	Lower initial maintenance dose (100-200 mg/day) due to increased half-life; monitor for bradycardia and thyroid dysfunction.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CORDARONE (CORDARONE).

Breastfeeding	Cordarone and its metabolite desethylamiodarone are excreted in breast milk. Milk-to-plasma ratio approximately 0.2-1.4. Avoid breastfeeding due to potential neonatal hypothyroidism and iodine accumulation. Consider alternative if breastfeeding desired.
Teratogenic Risk	First trimester: Fetal iodine exposure from Cordarone may cause fetal goiter and hypothyroidism. Second and third trimesters: Continued risk of fetal hypothyroidism, goiter, and potential neurodevelopmental effects. Use only if maternal benefit outweighs fetal risk.

Warnings & precautions

■ FDA Black Box Warning

Cordarone (amiodarone) is indicated only for the treatment of documented life-threatening recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. It can cause pulmonary toxicity (including hypersensitivity pneumonitis and interstitial/alveolar pneumonitis), hepatotoxicity, and exacerbation of arrhythmias.

Side Effect Profile

Serious Effects

Absolute Contraindications

Severe sinus node dysfunction causing marked sinus bradycardia, second- or third-degree AV block unless functioning pacemaker, cardiogenic shock, known hypersensitivity to amiodarone or any component, and history of iodine hypersensitivity.

Clinical Precautions

Precautions

Pulmonary toxicity (monitor with chest X-ray and pulmonary function tests), hepatotoxicity (monitor LFTs), thyroid abnormalities (hypo- or hyperthyroidism), ocular toxicity (corneal microdeposits), skin discoloration, peripheral neuropathy, proarrhythmia, and drug interactions.

Clinical Tips & Counseling

Drug interactions

Loading safety data…

CORDARONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CORDARONE (CORDARONE).

How it works

What the body does with it

Metabolism	Hepatic, primarily via CYP3A4 and CYP2C8; major metabolite is N-desethylamiodarone; also inhibits CYP1A2, CYP2C9, CYP2D6, CYP3A4, P-glycoprotein.
Excretion	Primarily hepatic metabolism with biliary excretion; minimal renal elimination (<1% unchanged). Fecal excretion accounts for ~70% of the dose. Less than 10% excreted in urine.
Half-life	Terminal half-life ranges 40–70 days (mean 55 days) due to extensive tissue accumulation, particularly in adipose tissue. Prolonged half-life necessitates loading doses and long washout periods.
Protein binding	99.7% bound, primarily to albumin and β-lipoproteins.
Volume of Distribution	Very large: 20–200 L/kg (mean 130 L/kg), reflecting extensive tissue distribution and accumulation in adipose, liver, lung, and myocardium.
Bioavailability	Oral: 20–55% (mean ~40%) due to variable absorption and first-pass metabolism. IV: 100%.
Onset of Action	IV: Within 2–3 hours for arrhythmia control. Oral: Days to weeks (2–7 days) due to slow accumulation; full antiarrhythmic effect may take 1–3 months.
Duration of Action	After discontinuation, antiarrhythmic effect persists for weeks to months due to extensive tissue stores (e.g., 4–6 months). Clinical monitoring required after cessation.

Classification & Brands

Action Class	Class III Agents- anti arrhythmic
Brand Substitutes	Amiojust 100mg Tablet, Amiodon 100mg Tablet, Amione 100mg Tablet, Eurythmic 100mg Tablet, Panarol 100mg Tablet, Duron 150mg Injection, Amiodon 150mg Injection, Eurythmic 150mg Injection, Cardasol 150mg Injection, Tachyra 150mg Injection

Dosing & administration

Dosage form	TABLET
Renal impairment	No adjustment required for GFR >10 mL/min. For GFR <10 mL/min, consider reducing maintenance dose by 25% due to accumulation of active metabolite.
Liver impairment	Child-Pugh A: No adjustment. Child-Pugh B: Reduce loading dose by 25-50% and maintenance by 25%. Child-Pugh C: Avoid use due to risk of toxicity.
Pediatric use	Loading: 10-20 mg/kg/day orally in 2 divided doses for 7-10 days, then 5-10 mg/kg/day for 5-7 days, then maintenance 2.5-5 mg/kg/day. IV: 5 mg/kg over 30 minutes, then 10-15 mg/kg/day continuous infusion.
Geriatric use	Lower initial maintenance dose (100-200 mg/day) due to increased half-life; monitor for bradycardia and thyroid dysfunction.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for CORDARONE (CORDARONE).

Breastfeeding	Cordarone and its metabolite desethylamiodarone are excreted in breast milk. Milk-to-plasma ratio approximately 0.2-1.4. Avoid breastfeeding due to potential neonatal hypothyroidism and iodine accumulation. Consider alternative if breastfeeding desired.
Teratogenic Risk	First trimester: Fetal iodine exposure from Cordarone may cause fetal goiter and hypothyroidism. Second and third trimesters: Continued risk of fetal hypothyroidism, goiter, and potential neurodevelopmental effects. Use only if maternal benefit outweighs fetal risk.