Pronestyl

PRONESTYL (procainamide hydrochloride), a Group 1A cardiac antiarrhythmic drug, is p-amino-N-{2-(diethylamino)ethyl}-benzamide monohydrochloride, molecular weight 271.79; its graphic formula is:

*(locus for acetylation to N-acetylprocainamide)

It differs from procaine which is the p-aminobenzoyl ester of 2-(diethylamino)-ethanol. Procainamide as the free base has a pKa of 9.23; the monohydrochloride is very soluble in water. PRONESTYL (procainamide hydrochloride) is supplied for oral administration as capsules and tablets in potencies of 250, 375, and 500 mg.

Inactive ingredients: Tablets—calcium silicate, microcrystalline cellulose, colorants (FD&C Yellow No. 5 (tartrazine) and Yellow No. 6), flavor, povidone, pregelatinized starch, stearic acid, and other ingredients.

Capsules—colorants (D&C Yellow No. 10, except 375 mg; FD&C Yellow No. 6), gelatin, lactose (except 500 mg); magnesium stearate, talc, and titanium dioxide.

PRONESTYL (procainamide hydrochloride) is 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 PRONESTYL (procainamide) , its use with lesser arrhythmias is generally not recommended. Treatment of patients with asymptomatic ventricular premature contractions should be avoided.

Initiation of PRONESTYL (procainamide) treatment, as with other antiarrhythmic agents used to treat life-threatening arrhythmias, should be carried out in the hospital.

Antiarrhythmic drugs have not been shown to enhance survival in patients with ventricular arrhythmias.

Because procainamide has the potential to produce serious hematological disorders (0.5 percent) particularly leukopenia or agranulocytosis (sometimes fatal), its use should be reserved for patients in whom, in the opinion of the physician, the benefits of treatment clearly outweigh the risks. (See WARNINGS and Boxed WARNING.)

Mortality

In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicentered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had myocardial infarctions more than six days but less than two years previously, an excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with encainide or flecainide (56/730) compared with that seen in patients assigned to matched placebo-treated groups (22/725). The average duration of treatment with encainide or flecainide in this study was ten months.

The applicability of these results to other populations (e.g., those without recent myocardial infarctions) or to other antiarrhythmic drugs is uncertain, but at present it is prudent to consider any antiarrhythmic agent to have a significant risk in patients with structural heart disease.

Blood Dyscrasias

Agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia and thrombocytopenia in patients receiving procainamide hydrochloride have been reported at a rate of approximately 0.5 percent. Most of these patients received procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20-25 percent mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, it is recommended that complete blood counts including white cell, differential and platelet counts be performed at weekly intervals for the first three months of therapy, and periodically thereafter. Complete blood counts should be performed promptly if the patient develops any signs of infection (such as fever, chills, sore throat or stomatitis), bruising or bleeding. If any of these hematologic disorders are identified, procainamide therapy should be discontinued. Blood counts usually return to normal within one month of discontinuation. Caution should be used in patients with pre-existing marrow failure of cytopenia of any type. (See ADVERSE REACTIONS.)

Digitalis Intoxication

Caution should be exercised in the use of procainamide in arrhythmias associated with digitalis intoxication. Procainamide can suppress digitalis-induced arrhythmias; however, if there is concomitant marked disturbance of atrioventricular conduction, additional depression of conduction and ventricular asystole or fibrillation may result. Therefore, use of procainamide should be considered only if discontinuation of digitalis, and therapy with potassium, lidocaine, or phenytoin are ineffective.

First Degree Heart Block

Caution should be exercised also if the patient exhibits or develops first degree heart block while taking PA, and dosage reduction is advised in such cases. If the block persists despite dosage reduction, continuation of PA administration must be evaluated on the basis of current benefit versus risk of increased heart block.

Predigitalization for Atrial Flutter or Fibrillation

Patients with atrial flutter or fibrillation should be cardioverted or digitalized prior to PA administration to avoid enhancement of A-V conduction which may result in ventricular rate acceleration beyond tolerable limits. Adequate digitalization reduces but does not eliminate the possibility of sudden increase in ventricular rate as the atrial rate is slowed by PA in these arrhythmias.

Congestive Heart Failure

For patients in congestive heart failure, and those with acute ischemic heart disease or cardiomyopathy, caution should be used in PA therapy, since even slight depression of myocardial contractility may further reduce cardiac output of the damaged heart.

Concurrent Other Antiarrhythmic Agents

Concurrent use of PA with other Group 1A antiarrhythmic agents such as quinidine or disopyramide may produce enhanced prolongation of conduction or depression of contractility and hypotension, especially in patients with cardiac decompensation. Such use should be reserved for patients with serious arrhythmias unresponsive to a single drug and employed only if close observation is possible.

Renal insufficiency

Renal insufficiency may lead to accumulation of high plasma levels from conventional oral doses of PA, with effects similar to those of overdosage (see OVERDOSAGE), unless dosage is adjusted for the individual patient.

Myasthenia Gravis

Patients with myasthenia gravis may show worsening of symptoms from PA due to its procaine-like effect on diminishing acetylcholine release at skeletal muscle motor nerve endings, so that PA administration may be hazardous without optimal adjustment of anticholinesterase medications and other precautions.

Procainamide affects the way your heart beats.

Procainamide is used to help keep the heart beating normally in people with certain heart rhythm disorders of the ventricles (the lower chambers of the heart that allow blood to flow out of the heart).

Procainamide may also be used for purposes not listed in this medication guide.

• Abnormal Heart Rhythms (Heart Rhythm Disorders)
• Atrial Fibrillation (AF, AFib)
• Palpitations

It is important that your doctor check your progress carefully while you are receiving this medicine to make sure it is working properly. This will allow necessary changes in the amount of medicine you receive and may also help reduce side effects.

Dizziness or lightheadedness may occur with this medicine, especially in elderly patients and when large doses are used. Patients should use extra care to avoid falling. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or not alert.

The prolonged administration of procainamide often leads to the development of a positive antinuclear antibody (ANA) test, with or without symptoms of a lupus erythematosus-like syndrome. If a positive ANA titer develops, the benefits versus risks of continued procainamide therapy should be assessed.

Cardiovascular

Hypotension following oral PA administration is rare. Hypotension and serious disturbances of cardiorhythm such as ventricular asystole or fibrillation are more common after (see OVERDOSAGE, WARNINGS). Second degree heart block has been reported in 2 of almost 500 patients taking PA orally.

Multisystem

A lupus erythematosus-like syndrome of arthralgia, pleural or abdominal pain, and some-times 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 (see Boxed WARNINGS and PRECAUTIONS). While some series have reported less than 1 in 500, others have reported the syndrome in up to 30 percent of patients on long term oral PA therapy. If discontinuation of PA does not reverse the lupoid symptoms, corticosteroid treatment may be effective.

Hematologic

Neutropenia, thrombocytopenia, or hemolytic anemia may rarely be encountered. Agranulocytosis has occurred after repeated use of PA, and deaths have been reported. (See Boxed WARNING, WARNINGS section.)

Skin

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

Gastrointestinal

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

Elevated Liver Enzymes

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.

Nervous System

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

Progressive widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves, as well as increasing A-V block, may be seen with doses which are excessive for a given patient. Increased ventricular extrasystoles, or even ventricular tachycardia or fibrillation may occur. After intravenous administration but seldom after oral therapy, transient high plasma levels of PA may induce hypotension, affecting systolic more than diastolic pressures, especially in hypertensive patients. Such high levels may also produce central nervous depression, tremor, and even respiratory depression.

Plasma levels above 10 µg/mL are increasingly associated with toxic findings, which are seen occasionally in the 10 to 12 µg/mL range, more often in the 12 to 15 µg/mL range, and commonly in patients with plasma levels greater than 15 µg/mL. Overdosage symptoms may result following a single 2 g dose while 3 g may be dangerous, especially if the patient is a slow acetylator, has decreased renal function, or underlying organic heart disease.

Treatment of overdosage or toxic manifestations includes general supportive measures, close observation, monitoring of vital signs and possibly intravenous pressor agents and mechanical cardiorespiratory support. If available, PA and NAPA plasma levels may be helpful in assessing the potential degree of toxicity and response to therapy. Both PA and NAPA are removed from the circulation by hemodialysis but not peritoneal dialysis. No specific antidote for PA is known.

Pronestyl Capsules (Procainamide Hydrochloride Capsules USP)

Pronestyl Tablets (Procainamide Hydrochloride Tablets USP)

Storage

Store at room temperature; avoid excessive heat (104° F); protect from moisture.

*FILMLOK is a Squibb trademark for veneer-coated tablets.

APOTHECON®
A Bristol-Myers Squibb Company
Princeton, NJ 08540