|Manufacturer:||Wyeth Pharmaceuticals Inc.|
Active Ingredient: amiodarone HCl Inactive Ingredients: colloidal silicon dioxide, lactose, magnesium stearate, povidone, starch, and FD&C Red 40.
This Medication Guide has been approved by the U.S.
Food and Drug Administration.
Rx onlyManufactured for Wyeth®Wyeth Pharmaceuticals Inc.
Philadelphia, PA 19101by Sanofi Winthrop Industrie 1, rue de la Vierge 33440 Ambares, FranceCordarone is a registered trademark of Sanofi-Synthelabo.
Tagamet is a registered trademark of SmithKline Beecham Pharmaceuticals Co.
Claritin is a registered trademark of Schering Corporation.
Alavert is a registered trademark of Wyeth.
©2004, Wyeth Pharmaceuticals.
All rights reserved.(Update W10427C017)(Update ET01)(Update Rev Date)
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.
Cordarone is contraindicated in patients with cardiogenic shock; severe sinus-node dysfunction, causing marked sinus bradycardia; second- or third-degree atrioventricular block; and when episodes of bradycardia have caused syncope (except when used in conjunction with a pacemaker).Cordarone is contraindicated in patients with a known hypersensitivity to the drug or to any of its components, including iodine.
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.