Cordarone (amiodarone hydrochloride) is a potent Class III antiarrhythmic agent with additional Class I, II, and IV properties, representing a cornerstone therapy for managing life-threatening ventricular and supraventricular arrhythmias. Its unique pharmacokinetic and pharmacodynamic profile allows for effective rhythm control in patients where other antiarrhythmic agents have failed or are contraindicated. Reserved for serious cardiac conditions due to its significant side effect profile, Cordarone requires meticulous patient selection, dosing, and long-term monitoring under specialist supervision to maximize therapeutic efficacy while minimizing potential toxicities.

Features

• Active Ingredient: Amiodarone Hydrochloride
• Pharmacological Class: Class III antiarrhythmic (with additional Class I, II, and IV activity)
• Available Formulations: Oral tablets (200mg) and intravenous (IV) solution for injection
• Mechanism of Action: Prolongs the cardiac action potential duration and refractory period via potassium channel blockade; exhibits non-competitive beta-adrenergic and calcium channel blockade
• Extremely Long Half-Life: Terminal elimination half-life ranges from 40 to 60 days, permitting once or twice-daily dosing after loading
• High Volume of Distribution: Extensive tissue sequestration, particularly in the liver, lungs, and fat

Benefits

• High Efficacy in Refractory Arrhythmias: Provides successful rhythm control in complex cases of ventricular tachycardia (VT), ventricular fibrillation (VF), and atrial fibrillation (AF) where other antiarrhythmics are ineffective.
• Reduces Hospitalizations: Effective maintenance therapy significantly decreases the frequency of arrhythmic episodes, leading to fewer emergency department visits and hospital admissions.
• Versatile Administration: Available in both oral and IV formulations allows for rapid initiation in acute settings (IV) and seamless transition to long-term oral maintenance therapy.
• Comprehensive Electrophysiological Action: Its multi-channel blockade offers a broad-spectrum approach to arrhythmia suppression, tackling multiple reentry pathways.
• Once-Daily Maintenance Dosing: The exceptionally long half-life facilitates convenient once-daily dosing for patients on long-term therapy, improving adherence.

Common use

Cordarone is indicated for the treatment of documented, recurrent, life-threatening ventricular arrhythmias, such as ventricular fibrillation (VF) and hemodynamically unstable ventricular tachycardia (VT), that do not respond to other antiarrhythmic agents or when other agents are not tolerated. Its use is typically reserved for these severe conditions due to its potential for serious toxicity. It is also used in the management of recurrent supraventricular arrhythmias, like atrial fibrillation and flutter, particularly in patients with structural heart disease (e.g., post-myocardial infarction, heart failure) where other antiarrhythmics may be pro-arrhythmic or contraindicated. Its use should be initiated and monitored by physicians experienced in the treatment of life-threatening arrhythmias.

Dosage and direction

Dosing is highly individualized and requires a loading phase to achieve therapeutic tissue levels rapidly, followed by a lower maintenance dose. Close supervision is mandatory.

Oral Administration:

• Loading Dose: Typically 800-1600 mg per day, divided into 2-3 doses, for 1-3 weeks. This is often initiated in a hospital setting.
• Continued Loading Dose: May be reduced to 600-800 mg per day for an additional 2-4 weeks.
• Maintenance Dose: The lowest effective dose should be used, commonly ranging from 200 mg to 400 mg once daily. Some patients may be maintained on 200 mg 5 days a week.

Intravenous (IV) Administration:

• Used for acute, life-threatening arrhythmias. A rapid loading infusion is administered, followed by a continuous maintenance infusion, with a transition to oral therapy as soon as clinically feasible.
• Initial Load: 150 mg over 10 minutes (15 mg/min), followed by 360 mg over the next 6 hours (1 mg/min), then 540 mg over the remaining 18 hours (0.5 mg/min).
• After the first 24 hours: A continuous maintenance infusion of 0.5 mg/min (720 mg/24 hours) is continued.

Crucial Direction: Cordarone must be taken consistently, with or without food, but the pattern (with/without food) should be kept constant. Tablets should not be crushed or chewed. The IV formulation must be administered via a central venous catheter due to the risk of peripheral vein phlebitis.

Precautions

• Baseline and Periodic Monitoring: A thorough baseline evaluation is required before initiation, including chest X-ray, pulmonary function tests (PFTs with DLCO), liver function tests (LFTs), thyroid function tests (TSH, T3, T4), and ophthalmologic examination. These must be repeated at regular intervals (e.g., every 3-6 months).
• Pulmonary Toxicity: This is the most serious non-cardiac side effect. Monitor for new or progressive dyspnea, cough, or pleuritic pain. Fatal pulmonary fibrosis has occurred.
• Hepatic Toxicity: Monitor LFTs regularly. Fatal hepatocellular necrosis has been reported. The drug should be discontinued or dosage reduced if AST/ALT levels exceed 3 times normal or double in a patient with elevated baseline levels.
• Thyroid Dysfunction: Cordarone can cause both hypothyroidism and hyperthyroidism. Monitor TSH levels.
• Ophthalmic Effects: Corneal microdeposits are common and usually benign, but periodic eye exams are recommended. Optic neuropathy/neuritis, which can lead to blindness, has been reported.
• Photosensitivity: Patients must be advised to use protective clothing and high-SPF sunscreen to avoid severe sunburn.
• Blue-Gray Skin Discoloration: Long-term therapy can cause a slate-blue or grayish pigmentation, primarily on sun-exposed areas.

Contraindications

• Known hypersensitivity to amiodarone, iodine, or any component of the formulation.
• Sinus nodal dysfunction, sinoatrial (SA) heart block, or 2nd or 3rd degree atrioventricular (AV) block not equipped with a functioning pacemaker.
• Marked sinus bradycardia or cardiogenic shock.
• Severe hepatic impairment.
• Use of drugs that prolong the QT interval and are known to cause Torsades de Pointes, where suitable alternatives are unavailable.

Possible side effect

Cordarone has a very extensive side effect profile, and most patients will experience at least one. Side effects can be dose- and duration-related.

Very Common (>10%): Corneal microdeposits (visual halos/light sensitivity), photosensitivity, nausea, vomiting, constipation, metallic taste, tremor/ataxia, bradycardia. Common (1-10%): Pulmonary toxicity (fibrosis, pneumonitis), elevated liver enzymes, hypothyroidism, hyperthyroidism, blue-gray skin discoloration, peripheral neuropathy, muscle weakness, sleep disturbances, elevated serum creatinine. Uncommon (<1%): Progressive liver disease/failure, optic neuropathy/neuritis (potential for blindness), sinus arrest, AV block, proarrhythmia (including Torsades de Pointes), Stevens-Johnson syndrome, toxic epidermal necrolysis, blood dyscrasias.

Drug interaction

Cordarone is a potent inhibitor of multiple CYP450 enzymes (CYP3A4, CYP2C9, CYP2D6) and P-glycoprotein, leading to a high potential for significant drug-drug interactions. It also increases the QT interval, creating an additive risk with other QT-prolonging drugs.

• QT-Prolonging Agents (e.g., fluoroquinolones, macrolides, antipsychotics, TCAs): Concomitant use is generally contraindicated due to significantly increased risk of Torsades de Pointes.
• Warfarin: Cordarone potentiates warfarin’s anticoagulant effect, increasing the risk of bleeding. Warfarin dose must be reduced by 25-50% and INR monitored very closely.
• Digoxin: Cordarone can double serum digoxin concentrations. The digoxin dose should be halved upon initiation of Cordarone and levels monitored.
• Statin Metabolism (especially Simvastatin, Lovastatin): Increased risk of myopathy/rhabdomyolysis. Use a lower dose of these statins or prefer pravastatin/rosuvastatin.
• Beta-Blockers, Calcium Channel Blockers: Additive effects on heart rate and AV conduction can lead to profound bradycardia and heart block.
• Cyclosporine: Increased plasma levels of cyclosporine, requiring dose reduction and monitoring.
• Phenytoin: Cordarone increases phenytoin levels; phenytoin may increase Cordarone metabolism.

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 never take a double dose to make up for a 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. Patients should be instructed to maintain their regular schedule and inform their physician of any pattern of missed doses.

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 for amiodarone overdose. Treatment is entirely supportive and symptomatic. For bradycardia and AV block, atropine, beta-adrenergic agonists, or cardiac pacing may be used. For hypotension, inotropic vasopressor agents (e.g., dopamine, norepinephrine) and IV fluids should be administered. Due to the drug’s long half-life and extensive tissue binding, prolonged monitoring and supportive care are necessary. Hemodialysis and hemoperfusion are not effective.

Storage

• Store at room temperature (20°C to 25°C or 68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F to 86°F).
• Protect from light and moisture. Keep the bottle tightly closed.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the packaging.
• Do not flush unused medication down the toilet or pour it into a drain. Dispose of it through a medicine take-back program or according to FDA guidelines.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting, stopping, or changing any prescribed part of your care plan. Never disregard professional medical advice or delay in seeking it because of something you have read here. The prescribing information provided by the manufacturer is the ultimate authority.

Reviews

“Cordarone remains an irreplaceable tool in our electrophysiology arsenal for managing malignant VT/VF. Its efficacy is unparalleled, but it demands immense respect. My practice involves a strict protocol of baseline and quarterly monitoring for pulmonary, hepatic, and thyroid function. In the right patient, with meticulous management, it is a life-saving drug.” – Cardiac Electrophysiologist, 15 years experience

“The side effect profile is daunting, and I reserve it strictly for patients with no other options. The long half-life is a double-edged sword: great for adherence, but a nightmare if toxicity develops. Patient education on photosensitivity and the importance of follow-up is absolutely critical.” – Clinical Cardiologist, 10 years experience

“As a pharmacist, my role is to be the gatekeeper for interactions. Every new Cordarone prescription triggers a deep dive into the patient’s entire medication list. The interactions with warfarin and digoxin are particularly dangerous and require immediate physician collaboration for dose adjustment.” – Clinical Pharmacist, Hospital Setting