indication

For the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias. It is a Class Ia antiarrhythmic drug.

pharmacology

Disopyramide is an antiarrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. In man, Disopyramide at therapeutic plasma levels shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

mechanism of action

Disopyramide is a Type 1A antiarrhythmic drug (ie, similar to procainamide and quinidine). It inhibits the fast sodium channels. In animal studies Disopyramide 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.

toxicity

LD₅₀=580 mg/kg in rats

biotransformation

Hepatic

absorption

Nearly complete

half life

6.7 hours (range 4-10 hours)

route of elimination

In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.

drug interactions

Acebutolol: Acebutolol may decrease symptoms of hypoglycemia and increase the time required for the body to compensate for hypoglycemia.

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Atenolol: The beta-blocker, atenolol, may increase the toxicity of disopyramide.

Azithromycin: The macrolide, azithromycin, may increase the effect of disopyramide.

Betaxolol: The beta-blocker, betaxolol, may increase the toxicity of disopyramide.

Bevantolol: The beta-blocker, bevantolol, may increase the toxicity of disopyramide.

Bisoprolol: The beta-blocker, bisoprolol, may increase the toxicity of disopyramide.

Butabarbital: arbiturates may increase the metabolism of Disopyramide. Monitor for decreased therapeutic effects of disopyramide if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased.

Carteolol: The beta-blocker, carteolol, may increase the toxicity of disopyramide.

Carvedilol: The beta-blocker, carvedilol, may increase the toxicity of disopyramide.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Clarithromycin: Increased risk of cardiotoxicity and arrhythmias

Donepezil: Possible antagonism of action

Erythromycin: Increased risk of cardiotoxicity and arrhythmias

Esmolol: The beta-blocker, esmolol, may increase the adverse effects of disopyramide.

Ethotoin: The hydantoin decreases the effect of disopyramide

Fosphenytoin: The hydantoin decreases the effect of disopyramide

Galantamine: Possible antagonism of action

Gatifloxacin: Increased risk of cardiotoxicity and arrhythmias

Grepafloxacin: Increased risk of cardiotoxicity and arrhythmias

Labetalol: The beta-blocker, labetolol, may increase the toxicity of disopyramide.

Levofloxacin: Increased risk of cardiotoxicity and arrhythmias

Mephenytoin: The hydantoin decreases the effect of disopyramide

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Metoprolol: The beta-blocker, metoprolol, may increase adverse effects of disopyramide.

Moxifloxacin: Increased risk of cardiotoxicity and arrhythmias

Nadolol: The beta-blocker, nadolol, may increase the toxicity of disopyramide.

Omeprazole: The beta-blocker increases toxicity of disopyramide

Oxprenolol: The beta-blocker, oxprenolol, may increase the toxicity of disopyramide.

Penbutolol: The beta-blocker, penbutolol, may increase the toxicity of disopyramide.

Phenobarbital: Phenobarbital decreases levels of disopyramide

Phenytoin: The hydantoin decreases the effect of disopyramide

Pindolol: The beta-blocker, pindolol, may increase the toxicity of disopyramide.

Practolol: The beta-blocker, practolol, may increase the toxicity of disopyramide.

Propranolol: The beta-blocker, propranolol, may increase the toxicity of disopyramide.

Quinupristin: This combination presents an increased risk of toxicity

Ranolazine: Possible additive effect on QT prolongation

Rifampin: Rifampin decreases the effect of disopyramide

Rivastigmine: Possible antagonism of action

Sotalol: The beta-blocker, sotalol, may increase the toxicity of disopyramide.

Sparfloxacin: Increased risk of cardiotoxicity and arrhythmias

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Telithromycin: Telithromycin may reduce clearance of Disopyramide. Concomitant therapy should be avoided.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

Thiopental: Thiopental may increase the metabolism and clearance of Disopyramide. Monitor for changes in therapeutic/adverse effects of Disopyramide if Thiopental is inititaed, discontinued or dose changed.

Thioridazine: Increased risk of cardiotoxicity and arrhythmias

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Timolol: The beta-blocker, timolol, may increase the toxicity of disopyramide.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Voriconazole: Additive QTc prolongation may occur. Voriconazole, a strong CYP3A4 inhibitor, may also increase the serum concentration of disopyramide by decreasing its metabolism. Consider alternate therapy or monitor for QTc prolongation and changes in the therapeutic and adverse effects of disopyramide if voriconazole is initiated, discontinued or dose changed.

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy should be avoided.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).