Cordarone (amiodarone hydrochloride) is a highly potent Class III antiarrhythmic agent with additional Class I, II, and IV properties, making it one of the most versatile and effective pharmacological tools for managing life-threatening ventricular and supraventricular arrhythmias. Its unique pharmacokinetic profile, characterized by a large volume of distribution and an exceptionally long half-life, necessitates a specialized approach to dosing and patient monitoring. This comprehensive guide details its appropriate use, mechanisms, and critical safety considerations for healthcare professionals managing complex cardiac electrophysiology.

Features

• Active Ingredient: Amiodarone Hydrochloride
• Pharmacological Class: Class III antiarrhythmic (with additional Class I, II, and IV activity)
• Available Formulations: Oral tablets (200 mg) and intravenous (IV) solution (150 mg/3 mL)
• Mechanism of Action: Prolongs phase 3 of the cardiac action potential (potassium channel blockade), non-competitive alpha- and beta-adrenergic inhibition, and weak sodium channel blockade.
• Bioavailability: Approximately 50% for oral administration, with significant inter-individual variation.
• Half-life: Extremely long and variable; 40-55 days following chronic oral dosing. A loading dose phase is required to achieve therapeutic levels.
• Protein Binding: >96%
• Metabolism: Extensive hepatic metabolism primarily via CYP3A4 and CYP2C8 to the active metabolite, desethylamiodarone.
• Excretion: Primarily via the biliary/faecal route; not dialyzable.

Benefits

• Superior Efficacy in Refractory Arrhythmias: Provides high-rate conversion and suppression of arrhythmias that have been unresponsive to other antiarrhythmic agents.
• Reduces Hospitalization and Mortality: In specific patient populations (e.g., post-MI with LV dysfunction), it has been shown to reduce arrhythmic death, though its overall mortality benefit is complex and context-dependent.
• Versatile Administration: Available in both oral and IV formulations, allowing for rapid IV loading in acute, life-threatening situations and transition to long-term oral maintenance therapy.
• Long Half-Life Facilitates Dosing Adherence: The extended elimination half-life provides a buffer against missed doses, maintaining a therapeutic effect.
• Positive Inotropic Effects are Minimal: Unlike many other antiarrhythmics, it has little negative inotropic effect, making it a viable option in patients with compromised left ventricular function.

Common use

Cordarone is reserved for the treatment of documented, life-threatening, recurrent ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT) when these arrhythmias have not responded to or are not tolerated with other antiarrhythmic agents. Its use in atrial fibrillation (AF) and flutter is generally for rhythm control in patients where other agents are contraindicated, ineffective, or not tolerated, particularly in the presence of structural heart disease (e.g., significant left ventricular hypertrophy, heart failure). It is not a first-line agent due to its significant and potentially severe adverse effect profile.

Dosage and direction

Dosing is highly individualized and requires a loading phase to achieve therapeutic serum concentrations rapidly, followed by a lower maintenance dose. Close monitoring is mandatory.

Oral Administration:

• Loading Dose: 800-1600 mg per day, divided into two doses, for 1-3 weeks until adequate arrhythmia control is achieved or side effects emerge.
• Maintenance Dose: Typically reduced to 400-600 mg per day for one month, then further reduced to the lowest effective dose, usually 200-400 mg daily. Some patients may be maintained on 200 mg every other day or 200 mg daily for 5 days a week.

Intravenous (IV) Administration (for acute, life-threatening arrhythmias):

• Initial Rapid Infusion: 150 mg over the first 10 minutes (15 mg/min). May be repeated every 10 minutes as needed for recurrent VF/VT.
• Slow Infusion: Following initial loading, a continuous infusion of 360 mg over the next 6 hours (1 mg/min).
• Maintenance Infusion: 540 mg over the remaining 18 hours (0.5 mg/min). After the first 24 hours, continue a maintenance infusion of 0.5 mg/min.
• Transition to Oral Therapy: IV therapy beyond 2-3 days is not recommended. Transition to oral therapy should be initiated as soon as feasible, with the oral loading dose commencing simultaneously with the IV taper.

Precautions

Cordarone therapy demands rigorous and proactive monitoring due to its multi-organ toxicity potential.

• Baseline and Periodic Testing: Obtain baseline chest X-ray, pulmonary function tests (including DLCO), liver transaminases, thyroid function tests (TSH, T3, T4), and ophthalmologic exam. Repeat at regular intervals (e.g., liver and thyroid function every 6 months, chest X-ray/annual PFTs if symptomatic).
• Pulmonary Toxicity: Can manifest as interstitial pneumonitis, pulmonary fibrosis, and ARDS. Monitor for new or worsening dyspnea, cough, or fever. This can be fatal and may require discontinuation.
• Hepatic Toxicity: Commonly causes elevated liver enzymes. Can progress to cirrhosis and liver failure. Monitor AST/ALT periodically.
• Thyroid Dysfunction: Can cause both hypothyroidism (more common) and hyperthyroidism. Monitor TSH levels.
• Corneal Microdeposits: Virtually all patients on long-term therapy develop corneal deposits; these are usually benign but can cause visual halos. Regular ophthalmologic exams are advised.
• Photosensitivity: Severe sunburn can occur with minimal sun exposure. Patients must use sunblock and protective clothing.
• Neurologic Effects: Peripheral neuropathy and myopathy may occur.
• Blue-Gray Skin Discoloration: Can occur with long-term use, typically in sun-exposed areas.

Contraindications

• Known hypersensitivity to amiodarone, iodine, or any component of the formulation.
• Severe sinus-node dysfunction or second- or third-degree AV block, unless a functioning pacemaker is present.
• Cardiogenic shock.
• Marked sinus bradycardia (except in the context of life-threatening arrhythmias where all other measures have failed).

Possible side effect

Side effects are frequent and often dose-related.

• Very Common (>10%): Nausea, vomiting, corneal microdeposits, photosensitivity, asymptomatic elevated liver enzymes, tremor/ataxia, blue-gray skin discoloration.
• Common (1-10%): Bradycardia, thyroid dysfunction (hypo- or hyper-), peripheral neuropathy, pulmonary toxicity (cough, dyspnea), insomnia.
• Uncommon (0.1-1%): Hepatitis, cirrhosis, visual disturbances/optic neuritis, proarrhythmia (torsades de pointes—risk is lower than with other Class III agents but present), Stevens-Johnson syndrome.
• Rare (<0.1%): Acute respiratory distress syndrome (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP), pulmonary fibrosis, pancreatitis.

Drug interaction

Cordarone is a potent inhibitor of multiple CYP450 enzymes (CYP3A4, CYP2C9, CYP2D6) and P-glycoprotein. It interacts with numerous drugs, often increasing their plasma concentrations and toxicity risk.

• QT-Prolonging Agents: Concomitant use with other drugs that prolong the QT interval (e.g., phenothiazines, tricyclic antidepressants, certain macrolides, fluoroquinolones) increases the risk of torsades de pointes.
• Warfarin: Potentiates anticoagulant effect; can increase INR by 100%. Reduce warfarin dose by 33-50% and monitor INR closely.
• Digoxin: Can double digoxin serum levels. Reduce digoxin dose by 50% and monitor levels.
• Statin Therapy: Increases risk of myopathy/rhabdomyolysis with simvastatin and lovastatin (CYP3A4 substrates). Use a lower dose of these statins or prefer pravastatin/rosuvastatin.
• Beta-Blockers, Calcium Channel Blockers: Potentiates bradycardia and AV block.
• Cyclosporine: Increases cyclosporine levels; monitor and adjust dose.
• Phenytoin, Fentanyl: Increases levels of these drugs.
• Selective Serotonin Reuptake Inhibitors (SSRIs): Increased risk of serotonin syndrome.

Missed dose

If a dose is missed, it should be taken as soon as it is remembered. However, if it is almost time for the next scheduled dose, the missed dose should be skipped. The patient should not double the next dose to make up for the missed one. Due to the drug’s extremely long half-life, a single missed dose is unlikely to have a significant clinical impact on arrhythmia control.

Overdose

Symptoms: The most prominent manifestations of overdose are bradycardia, hypotension, cardiogenic shock, AV block, and QT prolongation. Hepatotoxicity and coma may also occur. Management: There is no specific antidote. Treatment is supportive and symptomatic. Bradycardia and AV block should be managed with beta-adrenergic agonists or temporary pacing. Hypotension may require inotropic support. Cordarone and its metabolite are not dialyzable. Continuous ECG and vital sign monitoring in an intensive care setting is essential.

Storage

• Oral Tablets: Store at room temperature (20-25°C or 68-77°F) in a tight, light-resistant container. Protect from moisture.
• IV Solution: Store at room temperature. Protect from light. Do not freeze. IV solutions diluted in D5W are stable for 24 hours at room temperature and 48 hours under refrigeration. However, due to the risk of phlebitis at the infusion site, concentrations should not exceed 2 mg/mL unless a central venous catheter is used.

Disclaimer

This information is intended for educational purposes and healthcare professionals only. It is not a substitute for professional medical advice, diagnosis, or treatment. The prescribing physician is responsible for determining the appropriate therapy for an individual patient, considering their complete medical history, contraindications, and potential drug interactions. Always consult official prescribing information and relevant clinical guidelines before initiating therapy with Cordarone.

Reviews

• “An indispensable, last-line agent in the electrophysiologist’s arsenal for managing malignant VT/VF. Its efficacy is unquestionable, but it demands immense respect and a disciplined monitoring protocol. The trade-off between benefit and toxicity is a constant consideration.” – Cardiac Electrophysiologist, 15 years experience
• “Managing the drug interactions is a full-time job. It effectively dictates the patient’s entire medication list. The pulmonary toxicity is the complication I fear the most.” – Clinical Pharmacist, Cardiology ICU
• “While newer agents have emerged, amiodarone remains the most effective drug for maintaining sinus rhythm in patients with heart failure and atrial fibrillation. We use it cautiously, but we use it often in this challenging population.” – Heart Failure Specialist
• “The long half-life is a double-edged sword. It’s forgiving for non-adherence but means adverse effects persist for weeks to months after discontinuation. Patient education on sun protection and reporting respiratory symptoms is critical.” – Cardiology Nurse Practitioner