Restricted for Use in Life-Threatening Arrhythmias
- Amiodarone is indicated for use only in patients with life threatening arrhythmia's because its use is associated with substantial toxicity.
- Potentially pulmonary fatal toxicities include hypersensitivity pneumonitis or interstitial /alveolar pneumonitis. Rates are as high as 10% to 17% in some series of patients with ventricular arrhythmia's given doses approximating 400 mg daily 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.
- Pro arrhythmic effects: 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 pro arrhythmic 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 amiodarone effectively and safely itself poses a significant risk in patients. Patients with the indicated arrhythmias must be hospitalized while the loading dose of this drug is administered, 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 decreases 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 events, and several series 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 dosage 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 anti arrhythmic agents when amiodarone must be stopped will be made difficult by the gradually, but unpredictably, changing amiodarone body burden. A similar problem exists when amiodarone is not effective; it still poses the risk of an interaction with whatever subsequent treatment is tried.
MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA
- Because absorption and elimination are variable, maintenance dose selection is difficult.
- Liver enzymes should be monitored on a regular basis in patients receiving relatively high maintenance therapy.
FDA and Industry Communications
Patient Counseling Information
Updated January 2018