indication

For the treatment of life-threatening ventricular arrhythmias.

pharmacology

Procainamide is an agent indicated for production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and quinidine. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.

mechanism of action

Procainamide is sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby effecting local anesthetic action.

toxicity

LD₅₀=95 mg/kg (rat, IV); LD₅₀=312 mg/kg (mouse, oral); LD₅₀=103 mg/kg (mouse, IV); LD₅₀=250 mg/kg (rabbit, IV)

biotransformation

Hepatic

absorption

75 to 95%

half life

~2.5-4.5 hours

route of elimination

Trace amounts may be excreted in the urine as free and conjugated p-aminobenzoic acid, 30 to 60 percent as unchanged PA, and 6 to 52 percent as the NAPA derivative.

drug interactions

Amiodarone: Amiodarone may increase serum levels and toxicity of procainamide.

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

Cimetidine: The histamine H2-receptor antagonist, cimetidine, may increase the effect of procainamide.

Ciprofloxacin: Ciprofloxacin may increase the effect of procainamide.

Cisapride: Increased risk of cardiotoxicity and arrhythmias

Dihydroquinidine barbiturate: Quinidine increases the effect of procainamide

Donepezil: Possible antagonism of action

Galantamine: Possible antagonism of action

Levofloxacin: Levofloxacin may increase the effect of procainamide.

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

Mesoridazine: Increased risk of cardiotoxicity and arrhythmias

Ofloxacin: Ofloxacin may increase the effect of procainamide.

Quinidine: Quinidine increases the effect of procainamide

Quinidine barbiturate: Quinidine increases the effect of procainamide

Ranitidine: The histamine H2-receptor antagonist, ranitidine, may increase the effect of procainamide.

Ranolazine: Possible additive effect on QT prolongation

Rivastigmine: Possible antagonism of action

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

Terbinafine: Terbinafine may reduce the metabolism and clearance of Procainamide. Consider alternate therapy or monitor for therapeutic/adverse effects of Procainamide if Terbinafine is initiated, discontinued or dose changed.

Terfenadine: Increased risk of cardiotoxicity and arrhythmias

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.

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.

Trimethoprim: Trimethoprim may reduce the clearance of Procainamide. Alternative treatments should be considered. If Trimethoprim is initiated or the dose is increased, monitor for increased toxicity of Procainamide (e.g. QTc intervals, EKG, serum drug concentrations). If Trimethoprim is discontinued or the dose decreased, monitor for reduced effects of Procainamide.

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

Vardenafil: Increased risk of cardiotoxicity and arrhythmias

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

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).