"The U.S. Food and Drug Administration today notified Ranbaxy Laboratories, Ltd., that it is prohibited from manufacturing and distributing active pharmaceutical ingredients (APIs) from its facility in Toansa, India, for FDA-regulated drug product"...
(Generic versions may still be available.)
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In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term multi-centered 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 have been reported in patients receiving procainamide at a rate of approximately 0.5%. Most of these patients received procainamide hydrochloride 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 hydrochloride should be discontinued. Blood counts usually return to normal within one month of discontinuation. Caution should be used in patients with preexisting marrow failure or 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 aterial 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 contactility 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 wshow 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.
Immediately after initiation of PA therapy, 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.
After approximately two days, steady state plasma PA levels are produced following regular oral administration of a given dose of procainamide hydrochloride extended-release tablets at set intervals. After achieving and maintaining therapeutic plasma concentrations and satisfactory electrocardiographic and clinical responses, continued frequent periodic monitoring of vital signs and electrocardiograms is advised. If evidence of QRS widening of more than 25 percent or marked prolongation of the Q-T interval occurs, concern for overdosage is appropriate, and reduction in dosage is advisable if a 50 percent increase occurs. Elevated serum creatinine or urea nitrogen, reduced creatinine clearance, or history of renal insufficiency, as well as use in older patients (over age 50), provide grounds to anticipate that less than the usual dosage and longer time intervals between doses may suffice, since the urinary elimination of PA and NAPA may be reduced, leading to gradual accumulation beyond normally predicted amounts. If facilities are available for measurement of plasma PA and NAPA, or acetylation capability, individual dose adjustment for optimal therapeutic levels may be easier, but close observation of clinical effectivemess is the most important criterion.
In the longer term, periodic complete blood counts are useful to detect possible idiosyncratic hematologic effects of PA on neutrophil, platelet or red cell homeostasis; agranulocytosis has been reported to occur occasionally in patients on long-term PA therapy. A rising titer of serum ANA may precede clinical symptoms of the lupoid syndrome (see DESCRIPTION: Boxed Warning and ADVERSE REACTIONS). If the lupus erythematosus-like syndrome develops in a patient with recurrent life-threatening arrhythmias not controlled by other agents, corticosteroid suppressive therapy may be used concomitantly with PA. Since the PA induced lupoid syndrome rarely includes the dangerous pathologic renal changes, PA therapy may not necessarily have to be stopped unless the symptoms of serositis and the possibility of further lupoid effects are of greater risk than the benefit of PA in controlling arrhythmias. Patients with rapid acetylation capability are less likely to develop the lupoid syndrome after prolonged PA therapy.
Information for Patients
See PATIENT INFORMATION section.
Laboratory tests such as complete blood count (CBC), electrocardiogram, and serum creatinine or urea nitrogen may be indicated, depending on the clinical situation and periodic rechecking of the CBC and ANA may be helpful in early detection of untoward reactions.
See DRUG INTERACTIONS section.
Drug/Laboratory Test Interactions
Suprapharmacologic concentrations of lidocaine and meprobamate may inhibit fluorescence of PA and NAPA, and propranolol shows a native fluorescence close to the PA/NAPA peak wavelengths, so that tests which depend on fluorescence measurement may be affected.
Long term studies in animals have not been performed.
Teratogenic Effects: Pregnancy Category C: Animal reproduction studies have not been conducted with PA. It also is not known whether PA can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PA should be given to a pregnant woman only if clearly needed.
Both PA and NAPA are excreted in human milk, and absorbed by the nursing infant. Because of the potential for serious adverse reactions in nursing infants, a decision to discontinue nursing or the drug should be made, taking into account the importance of the drug to the mother.
Safety and effectiveness in pediatric patients have not been established.
Last reviewed on RxList: 12/8/2004
This monograph has been modified to include the generic and brand name in many instances.
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