Procainamide (PA) increases the effective refractory period of the atria, and to a lesser extent the bundle of His-Purkinje system and ventricles of the heart. It reduces impulse conduction velocity in the atria, His-Purkinje fibers, and ventricular muscle, but has variable effects on the atrioventricular (A-V) node, a direct slowing action and a weaker vagolytic effect which may speed A-V conduction slightly. Myocardial excitability is reduced in the atria, Purkinje fibers, papillary muscles, and ventricles by an increase in the threshold for excitation, combined with inhibition of ectopic pacemaker activity by retardation of the slow phase of diastolic depolarization, thus decreasing automaticity especially in ectopic sites. Contractility of the undamaged heart is usually not affected by therapeutic concentrations, although slight reduction of cardiac output may occur, and may be significant in the presence of myocardial damage. Therapeutic levels of PA may exert vagolytic effects and produce slight acceleration of heart rate, while high or toxic concentrations may prolong A-V conduction time or induce A-V block, or even cause abnormal automaticity and spontaneous firing by unknown mechanisms.

Procainamide Hydrochloride Injection is indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia, that, in the judgement of the physician, are life-threatening. Because of the proarrhythmic effects of procainamide, its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided. 

Direct injection into a vein or into tubing of an established infusion line should be done slowly at a rate not to exceed 50 mg per minute. It is advisable to dilute either the 100 mg/mL or the 500 mg/mL concentrations of procainamide hydrochloride prior to intravenous injection to facilitate control of dosage rate. Doses of 100 mg may be administered every 5 minutes at this rate until the arrhythmia is suppressed or until 500 mg has been administered, after which it is advisable to wait 10 minutes or longer to allow for more distribution into tissues before resuming.

 Alternatively, a loading infusion containing 20 mg of Procainamide Hydrochloride per mL (1 g diluted to 50 mL with 5% Dextrose Injection, USP) may be administered at a constant rate of 1 mL per minute for 25 to 30 minutes to deliver 500 to 600 mg of PA. Some effects may be seen after infusion of the first 100 or 200 mg; it is unusual to require more than 600 mg to achieve satisfactory antiarrhythmic effects.

Hypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common with intravenous administration of PA than with intramuscular administration.

A lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions (see below) is fairly common after prolonged PA administration, perhaps more often in patients who are slow acetylators.

Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered.

Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rash have also occurred.

Anorexia, nausea, vomiting, abdominal pain, diarrhea or bitter taste may occur in 3 to 4 percent of patients taking oral procainamide.

Dizziness or giddiness, weakness, mental depression and psychosis with hallucinations have been reported.

Elevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported.

Procainamide should not be administered to patients with complete heart block because of its effects in suppressing nodal or ventricular pacemakers and the hazard of asystole.

In patients sensitive to procaine or other ester type local anesthetics, cross sensitivity to PA is unlikely. However, it should be borne in mind, and PA should not be used if it produces acute allergic dermatitis, asthma, or anaphylactic symptoms.

An established diagnosis of systemic lupus erythematosus is a contraindication to PA therapy, since aggravation of symptoms is highly likely.

Hypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common with intravenous administration of PA than with intramuscular administration.

A lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, and sometimes arthritis, pleural effusion, pericarditis, fever, chills, myalgia, and possibly related hematologic or skin lesions (see below) is fairly common after prolonged PA administration, perhaps more often in patients who are slow acetylators.

Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered.

Angioneurotic edema, urticaria, pruritus, flushing, and maculopapular rash have also occurred.

Anorexia, nausea, vomiting, abdominal pain, diarrhea or bitter taste may occur in 3 to 4 percent of patients taking oral procainamide.

Dizziness or giddiness, weakness, mental depression and psychosis with hallucinations have been reported.

Elevations of transaminase with and without elevations of alkaline phosphatase and bilirubin have been reported. Some patients have had clinical symptoms (e.g., malaise, right upper quadrant pain). Deaths from liver failure have been reported.