Cordarone

Cordarone is an antiarrhythmic medication that affects the rhythm of heartbeats. It is used to help keep the heart beating normally in people with life-threatening heart rhythm disorders.

Product dosage: 100mg
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Product dosage: 200mg
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Cordarone (amiodarone hydrochloride) is a potent Class III antiarrhythmic agent with additional Class I, II, and IV properties, offering a unique and multifaceted approach to cardiac rhythm control. It is specifically formulated for the treatment of recurrent life-threatening ventricular arrhythmias, such as ventricular fibrillation and hemodynamically unstable ventricular tachycardia, particularly in patients unresponsive to or intolerant of other antiarrhythmic therapies. Its high efficacy is attributed to its complex pharmacokinetic and pharmacodynamic profile, including an exceptionally long half-life and extensive tissue distribution, making it a cornerstone therapy in cardiology for managing the most challenging arrhythmic cases under stringent medical supervision.

Features

• Active Ingredient: Amiodarone Hydrochloride
• Pharmacological Class: Class III Antiarrhythmic (with additional Class I, II, and IV properties)
• Available Formulations: Oral tablets and intravenous solution
• Mechanism of Action: Prolongs the myocardial cell action potential duration and refractory period by blocking potassium channels; also exhibits non-competitive alpha- and beta-adrenergic inhibition and weak calcium channel blockade.
• Bioavailability: Approximately 50% for oral administration
• Elimination Half-Life: Biphasic; initial half-life of 2.5–10 days, terminal half-life of 26–107 days (up to 142 days in some studies) due to extensive tissue sequestration.
• Protein Binding: Extensive (~96%)
• Metabolism: Hepatic, primarily via CYP3A4 and CYP2C8 to the active metabolite, desethylamiodarone.
• Excretion: Primarily biliary; not dialyzable.

Benefits

• Superior Efficacy: Provides highly effective control and suppression of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia where other antiarrhythmic agents have failed.
• Broad-Spectrum Action: Its multi-class electrophysiological effects make it effective against a wide range of both supraventricular and ventricular tachyarrhythmias.
• Long Duration of Action: The extraordinarily long half-life supports consistent therapeutic plasma levels, potentially simplifying long-term dosing regimens and improving adherence.
• Hemodynamic Stability: Unlike many other potent antiarrhythmics, intravenous Cordarone typically causes minimal negative inotropic effects, making it suitable for use in patients with compromised left ventricular function or heart failure.
• Life-Saving Intervention: Represents a critical therapeutic option for patients with life-threatening arrhythmias, significantly reducing the risk of sudden cardiac death.

Common use

Cordarone is rigorously indicated for the treatment of documented recurrent life-threatening ventricular arrhythmias. Its use is reserved for patients who have not responded to or cannot tolerate other antiarrhythmic agents due to its significant and potentially severe adverse effect profile. Common specific uses, always under the direction of a cardiologist or electrophysiologist, include:

• Recurrent ventricular fibrillation.
• Recurrent hemodynamically unstable ventricular tachycardia.
• As part of a treatment strategy in patients with an implantable cardioverter-defibrillator (ICD) to reduce the frequency of shocks.
• Management of certain atrial arrhythmias (e.g., atrial fibrillation or flutter) to maintain sinus rhythm, particularly in patients with structural heart disease where other antiarrhythmics are contraindicated.

Dosage and direction

Dosing is highly individualized based on the clinical setting (inpatient vs. outpatient), indication, patient response, and tolerance to side effects. Close monitoring is paramount.

Loading Dose (Oral): Typically 800-1600 mg per day, administered in divided doses, for 1 to 3 weeks until initial therapeutic response is achieved or side effects preclude further dosing. Intravenous Loading: Reserved for acute, life-threatening situations in a monitored hospital setting. A rapid infusion followed by a continuous maintenance infusion is standard, following specific hospital protocols. Maintenance Dose (Oral): After the loading period, the dose is gradually reduced to the lowest effective dosage. Usual maintenance doses range from 200 mg to 400 mg daily. Some patients may be maintained on as little as 100 mg daily or 200 mg 5 days per week. Administration: Oral tablets should be taken consistently with respect to meals to standardize absorption. The intravenous formulation is for hospital use only and must be administered via a central venous catheter due to the risk of phlebitis.

Precautions

Cordarone therapy mandates vigilant, long-term surveillance due to its toxic potential. Key precautions include:

• Baseline Assessments: A thorough baseline evaluation must include pulmonary function tests (including diffusion capacity), liver transaminases, thyroid function tests (TSH, T3, T4), and an ophthalmologic examination.
• Routine Monitoring: Regular follow-up is non-negotiable. This includes chest X-rays, pulmonary function tests, and serum liver enzyme and thyroid function tests every 3-6 months.
• Pulmonary Toxicity: The most serious toxicity is interstitial pneumonitis, which can be fatal. Patients must report any new or worsening shortness of breath, cough, or fever immediately.
• Hepatic Toxicity: Can cause elevated liver enzymes, hepatitis, and cirrhosis. Regular LFT monitoring is essential.
• Photosensitivity: Patients must use protective clothing and high-SPF sunscreen to avoid severe sunburn.
• Corneal Microdeposits: Virtually all patients on long-term therapy develop corneal deposits, which are usually benign but may cause visual halos; regular eye exams are advised.
• Neurological Effects: Peripheral neuropathy and myopathy have been reported.

Contraindications

Cordarone is absolutely contraindicated in patients with:

• 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 a life-threatening arrhythmia treatable only by Cordarone where a pacemaker is implanted).

Possible side effect

The side effect profile is extensive and often dose- and duration-dependent.

• Very Common (>10%): Corneal microdeposits, photosensitivity, nausea, vomiting, metallic taste, tremor/ataxia, blue-gray skin discoloration.
• Common (1-10%): Elevated liver enzymes, hypothyroidism or hyperthyroidism, pulmonary toxicity (cough, dyspnea), peripheral neuropathy, bradycardia, constipation.
• Uncommon (0.1-1%): Hepatitis, cirrhosis, optic neuritis/neuropathy (which may lead to blindness), proarrhythmia (e.g., torsades de pointes), Stevens-Johnson syndrome.
• Rare (<0.1%): Acute respiratory distress syndrome (ARDS), bronchiolitis obliterans organizing pneumonia (BOOP), neutropenia, thrombocytopenia.

Drug interaction

Cordarone is a potent inhibitor of multiple CYP450 enzymes (notably CYP3A4, CYP2C9) and P-glycoprotein, leading to numerous significant interactions. It also has a long interaction tail due to its persistence in the body for months after discontinuation.

• QT-Prolonging Agents: Concomitant use with other drugs that prolong the QT interval (e.g., certain antipsychotics, antibiotics, other antiarrhythmics) significantly increases the risk of torsades de pointes.
• Warfarin: Potentiates anticoagulant effect dramatically, increasing the risk of bleeding. Warfarin dose must be reduced by 33-50% and INR monitored closely.
• Digoxin: Increases digoxin serum levels, potentially leading to toxicity. Digoxin dose should be halved upon initiation of Cordarone.
• Statin Metabolism: Increases levels of simvastatin, lovastatin, and atorvastatin, raising the risk of myopathy/rhabdomyolysis. Use of pravastatin, rosuvastatin, or fluvastatin is preferred.
• Cyclosporine: Increases cyclosporine levels, requiring close monitoring and dose adjustment.
• Phenytoin & Fentanyl: Cordarone can increase levels of these drugs.
• Beta-Blockers & Calcium Channel Blockers: Increased risk of bradycardia and AV block.

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. Given the drug’s long half-life, a single missed dose is unlikely to have a significant clinical impact on arrhythmia control.

Overdose

Symptoms of overdose are primarily extensions of its pharmacological and toxic effects: bradycardia, AV block, hypotension, cardiogenic shock, hepatic dysfunction, and QT prolongation leading to torsades de pointes. There is no specific antidote. Management is supportive and includes continuous ECG and blood pressure monitoring. Treatment of bradycardia and heart block may require pacing. Inotropic agents may be needed for hypotension. Torsades de pointes is treated with magnesium sulfate, pacing, or isoproterenol. Cordarone and its metabolite are not dialyzable.

Storage

• Store oral tablets at room temperature (20°C to 25°C or 68°F to 77°F), in a tight, light-resistant container.
• Keep out of reach of children and pets.
• Do not use after the expiration date printed on the packaging.
• The intravenous formulation requires specific handling per institutional protocol.

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 use of Cordarone must be managed by a qualified healthcare professional familiar with its complex pharmacology and toxicology.

Reviews

• “As an electrophysiologist, Cordarone remains an indispensable, albeit challenging, tool in our arsenal. Its efficacy in suppressing malignant VT/VF in patients with advanced cardiomyopathy is unmatched. The key is meticulous, lifelong surveillance for pulmonary, thyroid, and hepatic toxicity. It demands respect.” – Dr. A. Sharma, MD, Cardiology.
• “From a clinical pharmacy perspective, managing a patient on amiodarone is a continuous process of vigilance. The drug interaction profile is one of the most complex, requiring constant review of the patient’s entire medication regimen, even months after discontinuation. Patient education on side effects, especially pulmonary symptoms, is critical.” – Clinical Pharmacist, Major Heart Center.
• “I’ve been on Cordarone for 5 years for recurrent VT after my MI. It has kept my ICD from firing, which I am grateful for. The blue tint to my skin in the sun was strange at first, and I have to get my blood checked often, but it’s a small price to pay for the peace of mind.” – Patient T.M. (Note: This patient testimonial is illustrative; individual experiences vary greatly.)