Pronestyl (Procainamide HCl)

PRONESTYL® PRONESTYL®-SR

Squibb

Procainamide HCl

Antiarrhythmic Agent

Action And Clinical Pharmacology: Procainamide 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 node, a direct slowing action and a weaker vagolytic effect which may speed atrioventricular 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 procainamide may exert vagolytic effects and produce slight acceleration of heart rate, while high or toxic concentrations may prolong atrioventricular conduction time or induce atrioventricular block, or even cause abnormal automaticity and spontaneous firing, by unknown mechanisms.

The ECG may reflect these effects by showing slight sinus tachycardia (due to the anticholinergic action) and widened QRS complexes and, less regularly, prolonged QT and PR intervals (due to longer systole and slower conduction), as well as some decrease in QRS and T wave amplitude. These direct effects of procainamide on electrical activity, conduction, responsiveness, excitability and automaticity are characteristic of a Group 1A antiarrhythmic agent, the prototype for which is quinidine; procainamide effects are very similar. However, procainamide has weaker vagal blocking action than does quinidine, does not induce alpha-adrenergic blockade, and is less depressing to cardiac contractility.

Pharmacokinetics: The action of procainamide begins almost immediately after i.v. administration. Following i.m. injection, the therapeutic effect appears in 15 to 60 minutes. Oral administration of procainamide capsules produces a therapeutic effect approximately 1 hour after a 1 g loading dose or 4 hours after initiating treatment every 3 hours with the maintenance dose. Peak plasma concentrations occur about 1 hour after oral administration, indicating an overall half-time for absorption of approximately 20 minutes. For ventricular arrhythmias, therapeutic plasma levels have been reported to be 3 to 10 µg/mL, with those for the majority of patients in the range of 4 to 8 µg/mL.

Procainamide’s apparent volume of distribution (Vd) is usually between 1.75 and 2.5 L/kg body weight. About 75% of the procainamide is concentrated in highly perfused tissues. Approximately 20% is bound to plasma albumin.

Following oral administration of the conventional procainamide capsule, over 90% is recovered in the urine as unchanged drug or metabolites indicating almost complete absorption of the drug.

On the average, about 60% (range 30 to 80%) of the drug is excreted unchanged. The half-time for elimination from the body may vary from 2.5 to 6 hours or longer. The plasma clearance of procainamide is 400 to 600 mL/minute; renal clearance is 200 to 400 mL/minute.

In humans, procainamide is acetylated, and N-acetylprocainamide (NAPA), an active metabolite, can be detected in both plasma and urine. The dose fraction of procainamide excreted as NAPA is extremely variable, ranging from 6% to 52%.

Following oral administration of sustained release tablets every 6 hours, the mean steady-state serum concentrations of procainamide and NAPA achieved are approximately equivalent to those of a comparable dose of the conventional capsule administered every 3 hours.

When 500 mg sustained release tablets were administered for 3 days, approximately 48% and 15% were recovered in the urine as procainamine and NAPA, respectively. Other metabolites e.g., free and conjugated p-aminobenzoic acid which usually account for about 10% of the dose, were not analyzed in this study.

Indications And Clinical Uses:

No antiarrhythmic drug has been shown to reduce the incidence of sudden death in patients with asymptomatic ventricular arrhythmias. Most antiarrhythmic drugs have the potential to cause dangerous arrhythmias; some have been shown to be associated with an increased incidence of sudden death. In light of the above, physicians should carefully consider the risks and benefits of antiarrhythmic therapy for all patients with ventricular arrhythmias.

Ventricular Arrhythmias: For the treatment of documented life-threatening ventricular arrhythmias, such as sustained ventricular tachycardia. Procainamide may also be used for the treatment of patients with documented symptomatic ventricular arrhythmias when the symptoms are of sufficient severity to require treatment. Because of the proarrhythmic effects of procainamide, its use should be reserved for patients in whom, in the opinion of the physician, the benefit of treatment clearly outweighs the risks.

For patients with sustained ventricular tachycardia, procainamide therapy should be initiated in the hospital. Hospitalization may also be required for certain other patients depending on their cardiac status and underlying cardiac disease.

The effects of procainamide in patients with recent myocardial infarction have not been adequately studied and, therefore, its use in this condition cannot be recommended.

Supraventricular Arrhythmias: In the treatment of atrial fibrillation, particularly if the condition is of recent development and the treatments of choice cannot be used or are ineffective. The drug may also be used in paroxysmal atrial tachycardia which cannot be controlled by reflex stimulation or by other measures.

Pronestyl-SR is a sustained release formulation indicated as maintenance therapy for patients stabilized on regular Pronestyl.

Contra-Indications: Hypersensitivity to the drug is an absolute contraindication; in this connection, cross sensitivity to procaine and related drugs must be borne in mind. Procainamide should not be administered to patients with complete atrioventricular heart block. Procainamide is also contraindicated in cases of high degree AV block unless an electrical pacemaker is operative. Procainamide should not be used in patients with myasthenia gravis.

Because of the possibility of precipitous lowering of blood pressure with i.v. procainamide, it should not be used in patients with severe congestive heart failure, renal failure or shock.

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

In the particular ventricular arrhythmia called torsades de pointes, Group 1A antiarrhythmic drugs are contraindicated. Administration of procainamide in such cases may aggravate this type of ventricular tachycardia instead of suppressing it.

Manufacturers’ Warnings In Clinical States: Mortality: The results of the Cardiac Arrhythmia Suppression Trial (CAST) in post-myocardial infarction patients with asymptomatic ventricular arrhythmias showed a significant increase in mortality and in non-fatal cardiac arrest rate in patients treated with encainide or flecainide compared with a matched placebo-treated group. CAST was continued using a revised protocol with the moricizine and placebo arms only. The trial was prematurely terminated because of a trend towards an increase in mortality in the moricizine treated group.

The applicability of these results to other populations or other antiarrhythmic agents is uncertain, but at present it is prudent to consider these results when using any antiarrhythmic agent.

Blood Dyscrasias: Agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia and thrombocytopenia in patients receiving procainamide have been reported at a rate of approximately 0.5%. Most of these patients received procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20 to 25% 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 3 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 1 month of discontinuation. Caution should be used in patients with pre-existing marrow failure or cytopenia of any type (see Adverse Effects).

Patients should be instructed to report promptly any flu type symptoms such as malaise and aches, as well as any soreness of the mouth, throat or gums, unexplained fever, skin rash, unusual bleeding or bruising, or symptoms that resemble arthritis or symptoms of an upper respiratory tract infection.

Positive ANA: The prolonged administration of procainamide often leads to the development of a positive anti-nuclear antibody (ANA) test with or without symptoms of lupus erythematosus-like syndrome. If a positive ANA titer develops, the benefit/risk ratio related to continued procainamide therapy should be assessed. This may necessitate discontinuation of procainamide and substitution of alternative antiarrhythmic therapy.

Sulfite Sensitivity: Pronestyl injection contains sodium bisulfite, that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible individuals.

The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic individuals.

Precautions: The solution intended for i.v. use should be diluted prior to administration (see Dosage).

Patients should be closely observed for possible hypersensitivity reactions, especially if procaine or local anesthetic sensitivity is suspected, and for muscular weakness if myasthenia gravis is a possibility.

During administration of the drug, evidence of untoward myocardial responses should be carefully watched for in all patients. In the presence of an abnormal myocardium, procainamide may at times produce untoward responses. In atrial fibrillation or flutter, the ventricular rate may increase suddenly as the atrial rate is slowed. Adequate digitalization reduces, but does not abolish this danger. If myocardial damage exists, ventricular tachycardia is particularly hazardous. Correction of atrial fibrillation, with resultant forceful contractions of the atrium, may cause a dislodgement of mural thrombi and produce an embolic episode. However, it has been suggested that in a patient who is already discharging emboli, procainamide is more likely to stop than to aggravate the process.

Adjustment of the heart rate in a patient who has developed ventricular tachycardia during an occlusive coronary episode should be carried out with extreme caution. Caution is also required in marked disturbances of atrioventricular conduction such as AV block, bundle branch block, or severe digitalis intoxication, where the use of procainamide may result in additional depression of conduction and ventricular asystole or fibrillation. Widening of the QRS complex on the ECG calls for extreme caution. The effects of procainamide in digitalis intoxication, particularly where the arrhythmia is accompanied by marked conduction disturbances, are unpredictable and fatalities have occurred.

ECG monitoring should be carried out during i.v. therapy and, whenever practical, during i.m. therapy. If ECGs give evidence of impending heart block, parenteral administration should be discontinued at once. Since patients with severe organic heart disease and ventricular tachycardia may also have complete heart block which is difficult to diagnose under these circumstances, this complication should always be kept in mind when treating ventricular arrhythmias with procainamide. If the ventricular rate is significantly slowed by procainamide without attainment of regular atrioventricular conduction, the drug should be discontinued and the patient re-evaluated as asystole may result under these circumstances.

Serious hypotension can result from peripheral vasodilation and by depressing myocardial contractility and cardiac output. At high plasma levels, procainamide may produce sinus tachycardia due to reflex sympathetic response to its hypotensive effect. Large doses may increase cardiac automaticity and can induce complete atrioventricular block, cardiac standstill or ventricular extrasystoles that may proceed to ventricular fibrillation. These effects on the myocardium are reflected in the ECG; a widening of the QRS complex occurs most consistently; less regularly, the PR and QT intervals are prolonged; and the QRS and T waves show some decrease in voltage. These actions of procainamide may be intensified in patients with congestive heart failure.

During the first day following acute myocardial infarction, absorption of oral procainamide can be very poor. Therefore, when warranted, it is suggested that the drug be administered i.m. or i.v.

Plasma procainamide and NAPA concentrations rise markedly with increases in BUN and correlate well with creatinine clearance. Should patients with impaired kidney function and/or liver disease receive unadjusted dosage, symptoms of overdosage (principally ventricular tachycardia and severe hypotension) may occur due to drug accumulation. Similarly, plasma concentrations have been found to be increased in elderly patients possibly due to declining renal function in this age group. The frequency of administration should be reduced in patients with renal or hepatic insufficiency or in elderly patients.

Plasma concentrations of procainamide and NAPA should be monitored in patients with renal disease, hepatic disease, cardiac failure or low cardiac output states.

In patients with cardiac failure or shock or in patients with low cardiac output and extrarenal azotemia, the apparent volume of distribution and/or the elimination rate of procainamide can decrease considerably for a given dose, thereby resulting in increased plasma concentrations. Such patients should therefore be carefully monitored and the dose or frequency of administration reduced if warranted.

Instances of a syndrome resembling systemic lupus erythematosus have been reported in connection with oral maintenance procainamide therapy. The mechanism of this lupus erythematosus-like syndrome is uncertain. Polyarthralgia, arthritis, fever, pleuritic pain and skin lesions are common symptoms; to a lesser extent myalgia, pleural effusion and pericarditis may occur. Rare cases of thrombocytopenia or Coombs’ positive hemolytic anemia have been reported, and may be related to this syndrome. Patients receiving procainamide for extended periods of time or in whom symptoms suggestive of lupus erythematosus-like syndrome appear, should have antinuclear antibody titers measured at regular intervals. The drug should be discontinued if there is a rising titer (ANA) or clinical symptoms of lupus erythematosus-like syndrome appear. Lupus erythematosus-like syndrome is usually reversible upon discontinuation of the drug. If discontinuation of the drug does not cause remission of the symptoms, steroid therapy may be effective. If lupus erythematosus-like syndrome develops in a patient with recurrent life-threatening arrhythmias not controllable by other antiarrhythmic agents, steroid suppressive therapy may be used concomitantly with procainamide.

Laboratory Tests: Laboratory tests including complete blood count, ECG, and serum creatinine or urea nitrogen may be indicated, depending on the clinical situation, and periodic checking of the complete blood count and antinuclear antibody is helpful in early detection of untoward reactions (see Warnings, Blood Dyscrasias).

Pregnancy: Animal reproduction studies have not been conducted with procainamide. It is also not known whether procainamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

There has been some evidence of the diffusion of procainamide across the placental membrane. Therefore, due to the potential accumulation and slow rate of elimination of procainamide and N-acetylprocainamide in the fetus, the potential benefit of the use of procainamide during pregnancy should be weighed against the possible hazard to the fetus.

Lactation: Both procainamide and N-acetylprocainamide are excreted in human milk, and absorbed by the nursing infant. Because of the potential for serious adverse reactions in nursing infants, a decision should be made to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Children: Safety and effectiveness in children have not been established.

Drug Interactions: Antiarrhythmics: Concurrent use with procainamide may result in additive or antagonistic cardiac effects and/or additive toxic effects. Dosage reduction may be necessary.

Concurrent use with Class I antiarrhythmic agents (e.g., 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 should be employed only if close observation is possible.

Concurrent use with amiodarone may result in increased plasma procainamide and N-acetylprocainamide concentrations and subsequent toxicity. The dosage of i.v. procainamide should be reduced by 20 to 30% during concomitant administration. In addition, additive electrophysiologic effects may occur during concomitant use with agents that prolong the QT interval.

Beta Blockers: Procainamide may potentiate the cardiac depressant action of beta blocking agents such as propranolol.

Anticholinergics: Procainamide enhances the anticholinergic effects. Extreme caution must be exercised with such a combination.

Anticholinesterases: Procainamide antagonizes the effect of anticholinesterases in myasthenia gravis and paralysis returns.

Antihypertensives: Procainamide may potentiate the hypotensive effects of thiazide diuretics and other antihypertensive agents. Adjustment of dosage may be required.

Cimetidine: It has been reported that the histamine H2-antagonist cimetidine reduces renal clearance of procainamide and NAPA resulting in higher plasma concentrations for longer durations. Caution should be exercised when administering these drugs concurrently especially in the elderly who have a reduced ability to clear all three. Dosage modification may be required.

Neuromuscular Blocking Agents: Procainamide potentiates the effects of skeletal muscle relaxants such as succinylcholine. It also may enhance or prolong the neuromuscular blocking activity of bacitracin, colistimethate, dihydrostreptomycin, gentamicin, gramicidin, kanamycin, neomycin, polymyxin B, streptomycin, and viomycin, producing respiratory depression.

Antibiotics: Procainamide has also been reported to interact with kanamycin, neomycin and streptomycin to cause apnea and muscle weakness, due to an additive neuromuscular blocking effect.

Trimethoprim: The renal clearance of procainamide and NAPA is reduced by trimethoprim, resulting in increased pharmacodynamic response.

Adverse Reactions: The overall incidence of adverse effects with procainamide is about 9.2%. The most commonly occurring are gastrointestinal upset 3.9%, cardiovascular effects (ventricular dysrhythmias, bradycardia, hypotension and shock) 3.3% and drug fever 1.6%.

The most serious adverse reactions reported are granulocytopenia and the development of ANA. Granulocytopenia is most likely to occur within the first 3 months of therapy. Prolonged administration of procainamide often leads to the development of a positive ANA test with or without symptoms of lupus erythematosus-like syndrome perhaps more often in patients who are slow acetylators.

Because procainamide is a peripheral vasodilator, rapid i.v. administration may produce transient but at times severe lowering of blood pressure, particularly in conscious patients. I.M. injection is less likely to be accompanied by serious falls in blood pressure, and hypotension following oral administration is rare. Serious disturbances of cardiac rhythm such as ventricular asystole or fibrillation are also more common with i.v. administration. Precautionary measures to be followed during i.v. injection are given in the section on Dosage.

Incidence greater than 1%: Elevated ANA, sometimes associated with drug-induced lupus syndrome. Gastrointestinal symptoms, especially with large oral doses: anorexia, nausea, vomiting, diarrhea. (In patients on long-term procainamide therapy with sustained release preparations, the above reactions have been reported with an incidence greater than 5%.)

Cardiovascular Effects: bradycardia, arrhythmias, cardiac failure, shock. Hypersensitivity reactions, which may be manifested by one or more of the following: pruritus, urticaria, angioneurotic edema, maculopapular rash, fever, eosinophilia, hypergammaglobulinemia, flushing.

Incidence less than 1%: granulocytopenia (incidence about 0.5%), sometimes resulting in death; thrombocytopenia; immune hemolytic anemia; convulsions; psychosis with hallucinations; confusion; mental depression; giddiness; lightheadedness; weakness; bitter taste.

Rare: hypotension, second degree heart block (oral route); a case was reported with fever and chills plus nausea, vomiting, abdominal pain, acute hepatomegaly, and a rise in serum glutamic oxaloacetic transaminase following a single dose of the drug; vasculitis (hypersensitivity-type).

Symptoms And Treatment Of Overdose: Symptoms: Signs and symptoms of overdosage of procainamide include severe hypotension, ventricular fibrillation, widening of the QRS complex, prolonged P-R- and Q-T intervals, lowering of the R and T waves, increasing A-V block, junctional tachycardia, intraventricular conduction delay, oliguria, lethargy, confusion, nausea and vomiting.

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 16 µg/mL. If available, procainamide and N-acetylprocainamide plasma levels may be helpful in assessing the potential degree of toxicity and response to therapy. Transient high plasma levels of procainamide may induce hypotension after i.v. administration, and occasionally after oral therapy. This hypotension affects systolic more than diastolic pressures, especially in hypertensive patients. Such high levels may also produce CNS depression, tremor, and even respiratory depression.

Treatment: If ingestion is recent, gastric lavage or emesis may reduce absorption. Dopamine, phenylephrine or norepinephrine may be helpful in reversing severe hypotensive responses.

Management of overdosage includes symptomatic treatment with ECG and blood pressure monitoring. Procainamide toxicity can usually be treated, if necessary, by administering vasopressors after adequate fluid volume replacement. I.V. infusion of 1/6 molar sodium lactate injection reportedly reduces the cardiotoxic effects of procainamide.

The urinary elimination of procainamide is proportional to the glomerular filtration rate but is also affected by changes in urinary pH. Procainamide is relatively lipid-soluble as a free base but the ionized form is not. Acid urine, therefore, leads to ion trapping of procainamide which enters the urine by passive diffusion from the plasma. Accordingly, renal clearance of procainamide can be considerably increased by maintaining a low urinary pH and high flow rates.

If procainamide toxicity causes severe hypotension and renal insufficiency, urinary elimination of procainamide and NAPA is decreased and hemodialysis may be required. Hemodialysis significantly reduces the serum half-life of procainamide and effectively removes procainamide and NAPA. Peritoneal dialysis is not effective.

It has been reported that one patient who ingested approximately 7 g of procainamide HCl recovered after treatment consisting of i.v. norepinephrine, i.v. furosemide, attempted volume expansion with albumin, and hemodialysis. Also reported is the case of an elderly patient who recovered after ingestion of approximately 19 g of procainamide HCl. The patient was treated with i.v. isoproterenol and i.v. epinephrine. The latter report suggested that insertion of a ventricular pacing electrode is a reasonable precautionary measure in case high grade AV block develops.

Dosage And Administration: Selection of the dose and route of administration should be made with the following in mind: The optimum plasma level is 4 to 8 µg/mL.

Therapeutic Urgency: Oral administration is preferred. When parenteral therapy is necessary, i.m. administration is the method of choice. I.V. use should be limited to emergencies and continuous ECG monitoring is mandatory when this route is used.

In elderly patients and in patients with impaired renal function (decreased creatinine clearance) excretion is delayed and reduced frequency of administration is required (see Precautions).

An alkaline urine indicates a reduction in excretion rate, and the necessity for reduced frequency of administration.

Patients with cardiac failure, shock, low cardiac output and extrarenal azotemia should be carefully monitored and the dose or frequency of administration reduced if necessary.

Excretion rates appear to be unchanged by furosemide and other diuretics but are decreased by the use of acetazolamide, due to the production of alkaline urine.

Following stabilization on i.v. therapy, conversion to oral procainamide should be carried out as soon as practical.

Should toxic or sub-therapeutic levels be suspected, the patient’s plasma procainamide should be determined and adjusted accordingly.

Patients vary in response to a dose of procainamide. Nevertheless, the following guidelines should be considered when deciding upon the patient’s actual requirements: Parenteral dose: I.M: If the oral route is not feasible because of vomiting or unreliable absorption, 0.5 to 1 g may be given i.m., repeated every 3 hours until oral therapy is possible.

I.V.: The 10% (100 mg/mL) solution can be used for i.v. administration. This solution should be further diluted to facilitate accurate control of dosage. The dose should be administered at a rate not greater than 25 to 50 mg/minute by either direct i.v. administration or infusion. Slow administration allows some initial tissue distribution. Solutions prepared with 5% dextrose should be discarded after 8 hours.

Caution: I.V. use of procainamide may be accompanied by a hypotensive response, sometimes precipitous. For this reason, the dose schedules described below should be monitored electrocardiographically, so that the drug may be stopped when the arrhythmia is interrupted or when excessive widening of the QRS complex or prolongation of the PR interval suggests the occurrence of myocardial toxicity. Patients should be kept in a supine position and blood pressure should be measured almost continuously during the i.v. administration. If the fall in blood pressure exceeds 15 mmHg, the i.v. administration should be temporarily discontinued. Solutions of phenylephrine HCl injection, or norepinephrine injection, should be available to counteract severe hypotensive responses.

Direct I.V. Administration: Each mL of the 10% (100 mg/mL) solution should be further diluted to 10 to 20 mL with 5% Dextrose Injection USP prior to direct i.v. administration to facilitate control of dosage rate.

To reduce the possibility of a hypotensive response, 100 mg doses may be administered every 5 minutes by direct i.v. injection, at a rate not exceeding 50 mg/minute, until the arrhythmia is suppressed or a dose of 1 g has been administered. Blood pressure must be monitored and the ECG read before each dose. An effect is usually seen after the first or second injection. It is unusual to require more than 5 or 6 injections to achieve satisfactory antiarrhythmic effects.

To maintain therapeutic levels, procainamide infusion may then be started at a rate of 2 to 6 mg of procainamide per minute (see Table I) depending on the patient’s body weight, circulatory condition and renal function.

I.V. Infusion: An alternative method of achieving and then maintaining a therapeutic plasma concentration is to infuse 500 to 600 mg of procainamide at a constant rate over a period of 25 to 30 minutes and then to change to another infusion for maintenance at a rate of 2 to 6 mg/minute.

I.V. therapy should be terminated as soon as the patient’s basic cardiac rhythm appears to be stabilized and, if indicated, the patient should be placed on oral procainamide maintenance therapy. A period of about 3 to 4 hours (1 half-life) should elapse after the last i.v. dose of procainamide before administering the first oral dose of procainamide.

Surgical Use: For arrhythmias occurring during surgery, the suggested parenteral dose is 0.5 to 1.0 g preferably given i.m.

Oral Dose: Capsules: For ventricular tachycardia: An initial loading dose of 1 g followed thereafter by a total daily dose of 50 mg/kg of body weight in divided doses at 3 hour intervals is recommended.

In atrial arrhythmias, an initial dose of 1.25 g may be followed in 1 hour by 0.75 g if there have been no ECG changes. A dose of 0.5 to 1 g may then be given every 2 hours until the arrhythmia is interrupted or the limit of tolerance is reached. Suggested maintenance dosage is 0.5 to 1 g every 4 to 6 hours.

Pronestyl-SR Tablets are a sustained release dosage form not intended for initial therapy. For initial therapy by oral administration, conventional oral formulations of procainamide are recommended (see Supplied). Patients stabilized to an appropriate dosage level can be transferred to an equivalent daily dosage regimen of sustained release tablets.

The duration of action of procainamide supplied in this sustained release form allows dosing at intervals of every 6 hours, which may encourage patient compliance.

For Ventricular Tachycardia: The suggested maintenance dosage of sustained release tablets is 50 mg/kg of body weight daily given in divided doses at 6 hour intervals

For Atrial Fibrillation and Paroxysmal Atrial Tachycardia: The suggested maintenance dosage of sustained release tablets is 0.5 to 1 g every 6 hours.

Patients should be advised not to break or chew the sustained release tablet, as this would interfere with designed dissolution characteristics.

Availability And Storage: Pronestyl: Capsules: 250 mg: Each yellow capsule contains: procainamide HCl 250 mg. Nonmedicinal ingredients: lactose, magnesium stearate and talc. Capsule shell: D&C yellow No. 10, FD&C yellow No. 6, gelatin, printing ink and titanium dioxide. Tartrazine-free. Bottles of 100.

375 mg: Each white and orange capsule contains: procainamide HCl 375 mg. Nonmedicinal ingredients: magnesium stearate and talc. Capsule shell: FD&C yellow No. 6, gelatin, printing ink and titanium dioxide. May or may not contain lactose. Tartrazine-free. Bottles of 100.

500 mg: Each yellow and orange capsule contains: procainamide HCl 500 mg. Nonmedicinal ingredients: magnesium stearate and talc. Capsule shell: D&C yellow No. 10 and FD&C yellow No. 6. May or may not contain lactose. Tartrazine-free. Bottles of 100.

Keep containers tightly closed. Store at room temperature.

Injection: Each mL of parenteral solution for i.m. or i.v. use contains: procainamide HCl 100 mg (10%). Nonmedicinal ingredients: benzyl alcohol 0.9% (w/v) and sodium bisulfite 0.09% as preservatives and water for injection. Hydrochloric acid or sodium hydroxide for pH adjustments (pH 4.0 to 6.0). Vials of 10 mL.

Store vials at room temperature (15 to 30°C) and protect from light, freezing and exposure to excessive heat. The 10% solution, which is colorless initially, may in time develop a slightly yellow color. This change does not prevent its use, but a solution which becomes discolored in any other way should not be used.

Pronestyl-SR: Each greenish-yellow, biconvex, oval, veneer-coated, sustained release tablet contains: procainamide HCl 500 mg. Nonmedicinal ingredients: carbomer 934P, carnauba wax, microcrystalline cellulose, povidone, silica gel and stearic acid. Coating: alcohol, D&C yellow No. 10, ethylcellulose, FD&C blue No. 2, hydroxypropyl cellulose, hydroxypropyl methylcellulose, printing ink, titanium dioxide and triethyl citrate. Bottles of 100. Store at room temperature; avoid excessive heat. (Shown in Product Recognition Section)

PRONESTYL® PRONESTYL®-SR Squibb Procainamide HCl Antiarrhythmic Agent

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