Disopyramide - Warnings and Precautions

WARNINGS Mortality 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-adrenoceptor 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- 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.