Disopyramide

What it is and how it works

Mechanisms of Action Norpace (disopyramide phosphate) is a Type 1 antiarrhythmic drug (i.e., similar to procainamide and quinidine). In animal studies Norpace decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

Indications

INDICATIONS AND USAGE Norpace and Norpace CR are indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgment of the physician, are life-threatening. Because of the proarrhythmic effects of Norpace and Norpace CR, their use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. Initiation of Norpace or Norpace CR treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital. Norpace CR should not be used initially if rapid establishment of disopyramide plasma levels is desired. Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Dosage and administration (summary)

DOSAGE AND ADMINISTRATION The dosage of Norpace or Norpace CR must be individualized for each patient on the basis of response and tolerance. The usual adult dosage of Norpace or Norpace CR is 400 to 800 mg per day given in divided doses. The recommended dosage for most adults is 600 mg/day given in divided doses (either 150 mg every 6 hours for immediate-release Norpace or 300 mg every 12 hours for Norpace CR). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (either 100 mg every 6 hours for immediate-release Norpace or 200 mg every 12 hours for Norpace CR).

Contraindications

CONTRAINDICATIONS Norpace and Norpace CR are contraindicated in the presence of cardiogenic shock, preexisting second-or third-degree AV block (if no pacemaker is present), congenital Q-T prolongation, or known hypersensitivity to the drug.

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%).

Pregnancy

Pregnancy Teratogenic Effects Norpace was associated with decreased numbers of implantation sites and decreased growth and survival of pups when administered to pregnant rats at 250 mg/kg/day (20 or more times the usual daily human dose of 12 mg/kg, assuming a patient weight of at least 50 kg), a level at which weight gain and food consumption of d…

Storage and supply

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F).

Source: Disopyramide Phosphate (Norpace) — US FDA prescribing information, 2026-08-24, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.