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Black Box Warning
Mortality
See full prescribing information for complete Boxed Warning.
In the National Heart, Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had a myocardial infarction more than 6 days but less than 2 years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3.0%). The average duration of treatment with encainide or flecainide in this study was 10 months.
The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of Disopyramide Phosphate and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of Disopyramide Phosphate as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
See full prescribing information for complete Boxed Warning.
In the National Heart, Lung and Blood Institute’s Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi-center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had a myocardial infarction more than 6 days but less than 2 years previously, an excessive mortality or non-fatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to carefully matched placebo-treated groups (3.0%). The average duration of treatment with encainide or flecainide in this study was 10 months.
The applicability of the CAST results to other populations (e.g., those without recent myocardial infarction) is uncertain. Considering the known proarrhythmic properties of Disopyramide Phosphate and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of Disopyramide Phosphate as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
Negative Inotropic Properties
Heart Failure/Hypotension
Disopyramide phosphate may cause or worsen congestive heart failure or produce severe hypotension as a consequence of its negative inotropic properties. Hypotension has been observed primarily in patients with primary cardiomyopathy or inadequately compensated congestive heart failure. Disopyramide phosphate should not be used in patients with uncompensated or marginally compensated congestive heart failure or hypotension unless the congestive heart failure or hypotension is secondary to cardiac arrhythmia. Patients with a history of heart failure may be treated with Disopyramide phosphate, but careful attention must be given to the maintenance of cardiac function, including optimal digitalization. If hypotension occurs or congestive heart failure worsens, disopyramide phosphate should be discontinued and, if necessary, restarted at a lower dosage only after adequate cardiac compensation has been established.
QRS Widening
Although it is unusual, significant widening (greater than 25%) of the QRS complex may occur during Disopyramide phosphate administration; in such cases disopyramide phosphate should be discontinued.
Q-T Prolongation
As with other Type 1 antiarrhythmic drugs, prolongation of the Q-T interval (corrected) and worsening of the arrhythmia, including ventricular tachycardia and ventricular fibrillation, may occur. Patients who have evidenced prolongation of the Q-T interval in response to quinidine may be at particular risk. As with other Type 1A antiarrhythmics, disopyramide phosphate has been associated with torsade de pointes.
If a Q-T prolongation of greater than 25% is observed and if ectopy continues, the patient should be monitored closely, and consideration given to discontinuing disopyramide phosphate.
Hypoglycemia
In rare instances significant lowering of blood-glucose values has been reported during disopyramide phosphate administration. The physician should be alert to this possibility, especially in patients with congestive heart failure, chronic malnutrition, hepatic, renal or other diseases, or drugs (e.g., beta blockers, alcohol) which could compromise preservation of the normal glucoregulatory mechanisms in the absence of food. In these patients, the blood-glucose levels should be carefully followed.
Concomitant Antiarrhythmic Therapy
The concomitant use of disopyramide phosphate with other Type 1A antiarrhythmic agents (such as quinidine or procainamide), Type 1C antiarrhythmics (such as encainide, flecainide or propafenone), and/or propranolol should be reserved for patients with life-threatening arrhythmias who are demonstrably unresponsive to single-agent antiarrhythmic therapy. Such use may produce serious negative inotropic effects, or may excessively prolong conduction. This should be considered particularly in patients with any degree of cardiac decompensation or those with a prior history thereof. Patients receiving more than one antiarrhythmic drug must be carefully monitored.
Heart Block
If first-degree heart block develops in a patient receiving disopyramide phosphate, the dosage should be reduced. If the block persists despite reduction of dosage, continuation of the drug must depend upon weighing the benefit being obtained against the risk of higher degrees of heart block. Development of second-degree AV block or third-degree AV block or unifascicular, bifascicular, or trifascicular block requires discontinuation of disopyramide phosphate therapy, unless the ventricular rate is adequately controlled by a temporary or implanted ventricular pacemaker.
Anticholinergic Activity
Because of its anticholinergic activity, disopyramide phosphate should not be used in patients with glaucoma, myasthenia gravis or urinary retention unless adequate overriding measures are taken; these consist of the topical application of potent miotics (e.g., pilocarpine) for patients with glaucoma, and catheter drainage or operative relief for patients with urinary retention. Urinary retention may occur in patients of either sex as a consequence of disopyramide phosphate administration, but males with benign prostatic hypertrophy are at particular risk. In patients with a family history of glaucoma, intraocular pressure should be measured before initiating disopyramide phosphate therapy. Disopyramide phosphate should be used with special care in patients with myasthenia gravis since its anticholinergic properties could precipitate a myasthenic crisis in such patients.
Precautions
General
Atrial Tachyarrhythmias
Patients with atrial flutter or atrial fibrillation should be digitalized prior to disopyramide phosphate administration to ensure that drug-induced enhancement of AV conduction does not result in an increase of ventricular rate beyond physiologically acceptable limits.
Patients with myocarditis or other cardiomyopathy may develop significant hypotension in response to the usual dosage of disopyramide phosphate, probably due to cardiodepressant mechanisms. Therefore, a loading dose of disopyramide phosphate should not be given to such patients, and initial dosage and subsequent dosage adjustments should be made under close supervision.
Adverse Reactions
Clinical Trials Experience
The adverse reactions which were reported in disopyramide phosphate clinical trials encompass observations in 1,500 patients, including 90 patients studied for at least 4 years. The most serious adverse reactions are hypotension and congestive heart failure. The most common adverse reactions, which are dose dependent, are associated with the anticholinergic properties of the drug. These may be transitory, but may be persistent or can be severe. Urinary retention is the most serious anticholinergic effect.
The following reactions were reported in 10% to 40% of patients:
Anticholinergic: Dry mouth, urinary hesitancy, constipation.
* Some cases of SLE (systmic lupus erythematosus) symptoms have been reported; most cases occurred in patients who had been switched to disopyramide from procainamide following the development of SLE symptoms.
Rarely, acute psychosis has been reported following disopyramide phosphate therapy, with prompt return to normal mental status when therapy was stopped.
Postmarketing Experience
There is limited information regarding Disopyramide Postmarketing Experience in the drug label.
