PACERONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PACERONE (PACERONE).

How it works

Class III antiarrhythmic agent; prolongs action potential duration and refractory period by blocking potassium channels, and also exhibits class I, II, and IV effects.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 and CYP2C8; active metabolite desethylamiodarone; substrate of P-glycoprotein.
Excretion	Primarily hepatic metabolism (CYP3A4, CYP2C8) to desethylamiodarone (active). Renal elimination of drug and metabolites: <1% of unchanged drug; ~40% of dose as metabolites. Fecal elimination: ~70% of dose as metabolites, with some parent drug.
Half-life	Biphasic: initial 3-10 days; terminal elimination half-life 40-58 days (mean ~53 days) due to extensive tissue distribution and slow release from fat. Clinical context: steady-state achieved in 2-4 months without loading dose.
Protein binding	96% bound, primarily to albumin and beta-lipoproteins.
Volume of Distribution	66 L/kg (range 10-200 L/kg) indicating extensive tissue distribution, especially in adipose tissue, liver, and lungs.
Bioavailability	Oral: 30-80% (mean ~50%), increased by food; erratic absorption due to high lipophilicity. IV: 100%.
Onset of Action	IV: within 2-3 hours for antiarrhythmic effect. Oral: 2-7 days; full effect may take weeks due to slow accumulation.
Duration of Action	Long; persists for weeks to months after discontinuation due to long half-life. Antiarrhythmic effect may last 30-45 days post-cessation.

Classification & Brands

Dosing & administration

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

Dosage form	TABLET
Renal impairment	No specific GFR-based dose adjustment required; caution in severe renal impairment due to possible accumulation of active metabolite desethylamiodarone. Monitor serum levels and QT interval.
Liver impairment	Contraindicated in severe hepatic disease (Child-Pugh class C). In moderate impairment (Child-Pugh class B), reduce maintenance dose by 50% and monitor liver function. Mild impairment (Child-Pugh A): no adjustment, but monitor.
Pediatric use	Loading: 10-20 mg/kg/day PO in divided doses for 7-10 days; maintenance: 5-10 mg/kg/day PO once daily. IV loading: 5 mg/kg over 30 min, then 5-15 mg/kg/day continuous infusion.
Geriatric use	Lower maintenance doses (100-200 mg/day PO) due to increased risk of bradycardia, QT prolongation, and thyroid dysfunction. Monitor renal function and electrolytes closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PACERONE (PACERONE).

Breastfeeding	Amiodarone is excreted into breast milk with an M/P ratio of approximately 0.1-1.0. Due to significant accumulation in infant tissues and long half-life, breastfeeding is contraindicated because of potential for neonatal hypothyroidism and bradycardia.
Teratogenic Risk	Pacerone (amiodarone) is FDA Pregnancy Category D. First trimester: risk of congenital anomalies including hypothyroidism, goiter, and neurodevelopmental delays due to iodine content. Second and third trimesters: continued risk of fetal hypothyroidism and bradycardia; neonatal monitoring for thyroid function and ECG is recommended.

Warnings & precautions

■ FDA Black Box Warning

Only for patients with life-threatening arrhythmias due to risk of pulmonary toxicity, hepatotoxicity, and proarrhythmia; requires baseline and periodic monitoring of pulmonary function, liver enzymes, thyroid function, and ECG.

Side Effect Profile

Serious Effects

Absolute Contraindications

Cardiogenic shock, severe sinus node dysfunction (without pacemaker), second- or third-degree AV block (without pacemaker), marked bradycardia, and hypersensitivity to amiodarone or iodine.

Clinical Precautions

Precautions

Pulmonary toxicity (interstitial pneumonitis, pulmonary fibrosis), hepatotoxicity (elevated liver enzymes, hepatic failure), proarrhythmia (worsening arrhythmias, torsades de pointes), thyroid dysfunction (hypo- or hyperthyroidism), optic neuropathy/neuritis, skin discoloration, photosensitivity, bradycardia, and drug interactions (CYP450 and P-gp mediated).

Clinical Tips & Counseling

Drug interactions

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PACERONE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for PACERONE (PACERONE).

How it works

Class III antiarrhythmic agent; prolongs action potential duration and refractory period by blocking potassium channels, and also exhibits class I, II, and IV effects.

What the body does with it

Metabolism	Primarily hepatic via CYP3A4 and CYP2C8; active metabolite desethylamiodarone; substrate of P-glycoprotein.
Excretion	Primarily hepatic metabolism (CYP3A4, CYP2C8) to desethylamiodarone (active). Renal elimination of drug and metabolites: <1% of unchanged drug; ~40% of dose as metabolites. Fecal elimination: ~70% of dose as metabolites, with some parent drug.
Half-life	Biphasic: initial 3-10 days; terminal elimination half-life 40-58 days (mean ~53 days) due to extensive tissue distribution and slow release from fat. Clinical context: steady-state achieved in 2-4 months without loading dose.
Protein binding	96% bound, primarily to albumin and beta-lipoproteins.
Volume of Distribution	66 L/kg (range 10-200 L/kg) indicating extensive tissue distribution, especially in adipose tissue, liver, and lungs.
Bioavailability	Oral: 30-80% (mean ~50%), increased by food; erratic absorption due to high lipophilicity. IV: 100%.
Onset of Action	IV: within 2-3 hours for antiarrhythmic effect. Oral: 2-7 days; full effect may take weeks due to slow accumulation.
Duration of Action	Long; persists for weeks to months after discontinuation due to long half-life. Antiarrhythmic effect may last 30-45 days post-cessation.

Classification & Brands

Dosing & administration

Dosage form	TABLET
Renal impairment	No specific GFR-based dose adjustment required; caution in severe renal impairment due to possible accumulation of active metabolite desethylamiodarone. Monitor serum levels and QT interval.
Liver impairment	Contraindicated in severe hepatic disease (Child-Pugh class C). In moderate impairment (Child-Pugh class B), reduce maintenance dose by 50% and monitor liver function. Mild impairment (Child-Pugh A): no adjustment, but monitor.
Pediatric use	Loading: 10-20 mg/kg/day PO in divided doses for 7-10 days; maintenance: 5-10 mg/kg/day PO once daily. IV loading: 5 mg/kg over 30 min, then 5-15 mg/kg/day continuous infusion.
Geriatric use	Lower maintenance doses (100-200 mg/day PO) due to increased risk of bradycardia, QT prolongation, and thyroid dysfunction. Monitor renal function and electrolytes closely.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for PACERONE (PACERONE).

Breastfeeding	Amiodarone is excreted into breast milk with an M/P ratio of approximately 0.1-1.0. Due to significant accumulation in infant tissues and long half-life, breastfeeding is contraindicated because of potential for neonatal hypothyroidism and bradycardia.
Teratogenic Risk	Pacerone (amiodarone) is FDA Pregnancy Category D. First trimester: risk of congenital anomalies including hypothyroidism, goiter, and neurodevelopmental delays due to iodine content. Second and third trimesters: continued risk of fetal hypothyroidism and bradycardia; neonatal monitoring for thyroid function and ECG is recommended.

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Cardiogenic shock, severe sinus node dysfunction (without pacemaker), second- or third-degree AV block (without pacemaker), marked bradycardia, and hypersensitivity to amiodarone or iodine.