BOX WARNING
Cordarone is intended for use only in patients with the indicated life-threatening arrhythmias because its use is accompanied by substantial toxicity.
Cordarone has several potentially fatal toxicities, the most important of which is pulmonary toxicity (hypersensitivity pneumonitis or interstitial/alveolar pneumonitis) that has resulted in clinically manifest disease at rates as high as 10 to 17% in some series of patients with ventricular arrhythmias given doses around 400 mg/day, and as abnormal diffusion capacity without symptoms in a much higher percentage of patients. Pulmonary toxicity has been fatal about 10% of the time. Liver injury is common with Cordarone, but is usually mild and evidenced only by abnormal liver enzymes. Overt liver disease can occur, however, and has been fatal in a few cases. Like other antiarrhythmics, Cordarone can exacerbate the arrhythmia, e.g., by making the arrhythmia less well tolerated or more difficult to reverse. This has occurred in 2 to 5% of patients in various series, and significant heart block or sinus bradycardia has been seen in 2 to 5%. All of these events should be manageable in the proper clinical setting in most cases. Although the frequency of such proarrhythmic events does not appear greater with Cordarone than with many other agents used in this population, the effects are prolonged when they occur.
Even in patients at high risk of arrhythmic death, in whom the toxicity of Cordarone is an acceptable risk, Cordarone poses major management problems that could be life-threatening in a population at risk of sudden death, so that every effort should be made to utilize alternative agents first.
The difficulty of using Cordarone effectively and safely itself poses a significant risk to patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of Cordarone is given, and a response generally requires at least one week, usually two or more. Because absorption and elimination are variable, maintenance-dose selection is difficult, and it is not unusual to require dosage decrease or discontinuation of treatment. In a retrospective survey of 192 patients with ventricular tachyarrhythmias, 84 required dose reduction and 18 required at least temporary discontinuation because of adverse effects, and several series have reported 15 to 20% overall frequencies of discontinuation due to adverse reactions. The time at which a previously controlled life-threatening arrhythmia will recur after discontinuation or dose adjustment is unpredictable, ranging from weeks to months. The patient is obviously at great risk during this time and may need prolonged hospitalization. Attempts to substitute other antiarrhythmic agents when Cordarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone body burden. A similar problem exists when Cordarone is not effective; it still poses the risk of an interaction with whatever subsequent treatment is tried.
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CORDARONE SUMMARY
Cordarone (amiodarone HCl) is a member of a new class of antiarrhythmic drugs with predominantly Class III (Vaughan Williams' classification) effects, available for oral administration as pink, scored tablets containing 200 mg of amiodarone hydrochloride.
Because of its life-threatening side effects and the substantial management difficulties associated with its use (see “WARNINGS” below), Cordarone is indicated only for the treatment of the following documented, life-threatening recurrent ventricular arrhythmias when these have not responded to documented adequate doses of other available antiarrhythmics or when alternative agents could not be tolerated.
- Recurrent ventricular fibrillation.
- Recurrent hemodynamically unstable ventricular tachycardia.
As is the case for other antiarrhythmic agents, there is no evidence from controlled trials that the use of Cordarone Tablets favorably affects survival.
Cordarone should be used only by physicians familiar with and with access to (directly or through referral) the use of all available modalities for treating recurrent life-threatening ventricular arrhythmias, and who have access to appropriate monitoring facilities, including in-hospital and ambulatory continuous electrocardiographic monitoring and electrophysiologic techniques. Because of the life-threatening nature of the arrhythmias treated, potential interactions with prior therapy, and potential exacerbation of the arrhythmia, initiation of therapy with Cordarone should be carried out in the hospital.
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NEWS HIGHLIGHTSMedia Articles Related to Cordarone (Amiodarone)
Sleep Disorders Linked to Arrhythmias
Source: MedicineNet Sleep Apnea Specialty [2009.06.24]
Title: Sleep Disorders Linked to Arrhythmias
Category: Health News
Created: 6/24/2009 7:00:00 AM
Last Editorial Review: 6/24/2009
Published Studies Related to Cordarone (Amiodarone)
Comparative efficacy of dronedarone and amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation. [2009.09.15]
OBJECTIVES: We sought to compare the efficacy and safety of dronedarone versus amiodarone for the prevention of recurrent atrial fibrillation (AF). BACKGROUND: Dronedarone is a noniodinated amiodarone congener developed to maintain sinus rhythm. Few data are available to directly compare the efficacy and safety of dronedarone versus amiodarone... CONCLUSIONS: Dronedarone is less effective than amiodarone for the maintenance of sinus rhythm, but has fewer adverse effects. For every 1,000 patients treated with dronedarone instead of amiodarone, we estimate approximately 228 more recurrences of AF in exchange for 9.6 fewer deaths and 62 fewer adverse events requiring discontinuation of drug.
A randomized trial evaluating amiodarone for prevention of atrial fibrillation after pulmonary resection. [2009.09]
BACKGROUND: Atrial fibrillation (AF) occurs commonly after anatomic pulmonary resection. In this study, the efficacy of amiodarone for prevention of post-pulmonary resection AF was investigated... CONCLUSIONS: Amiodarone prophylaxis significantly reduces the incidence of AF after anatomic pulmonary resection, and is associated with a significant reduction in length of intensive care unit stay.
Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation. [2009.07]
OBJECTIVES: To compare the clinical efficacy of intravenous diltiazem, digoxin, and amiodarone for acute ventricular rate (VR) control in patients with acute symptomatic atrial fibrillation (AF) necessitating hospitalization... CONCLUSIONS: As compared with digoxin and amiodarone, intravenous diltiazem was safe and effective in achieving VR control to improve symptoms and to reduce hospital stay in patients with acute AF.
Bioequivalence of 2 intravenous amiodarone formulations in healthy participants. [2009.04]
Intravenous amiodarone is an effective agent for the treatment of recurrent ventricular fibrillation and hemodynamically unstable ventricular tachycardia. PM101 is a new formulation of intravenous amiodarone that uses a cyclodextrin to maintain amiodarone in the aqueous phase... No safety concerns unique to PM101 were identified.
Prevention of atrial fibrillation after coronary artery bypass grafting via atrial electromechanical interval and use of amiodarone prophylaxis. [2009.04]
In our previous study, we defined a cut-off point of 120 ms for atrial electromechanical interval (AEMi) to determine the risk of atrial fibrillation (AF) occurrence. Accordingly, the present study sought to investigate whether or not a prophylactic perioperative administration of amiodarone could reduce the incidence of AF in a high-risk group (AEMi >120 ms) undergoing coronary artery bypass grafting (CABG)...
Clinical Trials Related to Cordarone (Amiodarone)
Effect of Prophylaxy of Amiodarone and Propranolol and Amiodarone With Propranolol in Prevention of Atrial Fibrillation Post Coronary Artery Bypass Graft [Completed]
Relative Bioavailability of PM101 IV and Cordarone IV [Completed]
Concentrations of Amiodarone in Fat Tissue During Chronic Treatment [Completed]
The objective of this study is to determine if concentrations of amiodarone in fat tissue
increase constantly over time during chronic treatment with this drug, and if blood
concentrations reflect accurately the concentrations in fat tissue or not. This is because
excessive concentrations of this drug in tissues can produce adverse effects.
Continuous Versus Episodic Amiodarone Treatment for the Prevention of Permanent Atrial Fibrillation [Completed]
Our hypothesis is that episodic amiodarone treatment (i. e. amiodarone treatment 1 month prior
until 1 month after cardioversion) is associated with a lower morbidity and a higher quality
of life compared to continuous prophylactic amiodarone treatment while atrial fibrillation is
still effectively suppressed. The latter means that at the end of the study permanent atrial
fibrillation is prevented in comparable percentage of patients (70%) in both treatment
strategies. However, this will be accomplished at the cost of a higher number of electrical
cardioversions (2-3) in the episodic treatment group compared to the continuous treatment
group.
A Phase III Superiority Study of Vernakalant vs Amiodarone in Subjects With Recent Onset Atrial Fibrillation [Recruiting]
The primary objective of the study is to demonstrate the superiority of vernakalant
injection over amiodarone injection in the conversion of atrial fibrillation (AF) to sinus
rhythm (SR) within 90 minutes of the start of drug administration. The secondary objective
is to compare the safety of vernakalant to amiodarone.
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Page last updated: 2009-10-20
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