Chemistry - Structurally related to procaine, procainamide is used as an antiarrhythmic agent. Procainamide HCl differs from procaine by the substitution of an amide group for the ester group found on procaine. It occurs as an odorless, white to tan, hygroscopic, crystalline powder with a pKa of 9.23 and a melting range from 165°-169°C. It is very soluble in water and soluble in alcohol. The pH of the injectable product ranges from 4 - 6.
Storage/Stability/Compatibility - Oxidation due to the injection of air into the vial may cause discoloration of the injectable solution. The solution may be used if the color is no darker than a light amber. Refrigeration may retard the development of oxidation, but the solution may be stored at room temperature.
The injectable product is reportedly compatible with sodium chloride 0.9% injection, and water for injection. Procainamide is also compatible with dobutamine HCl, lidocaine HCl, and verapamil HCl. Compatibility is dependent upon factors such as pH, concentration, temperature and diluents used. It is suggested to consult specialized references for more specific information (e.g., Handbook on Injectable Drugs by Trissel; see bibliography).
Pharmacology - A class 1A antiarrhythmic agent, procainamide exhibits cardiac actions similar to that of quinidine. Procainamide prolongs the refractory times in both the atria and ventricles, decreases myocardial excitability, and depresses automaticity and conduction velocity. It has anticholinergic properties which may contribute to its effects. Procainamide’s effects on heart rate are unpredictable, but it usually causes only slight increases or no change in heart rate. It may exhibit negative inotropic actions on the heart, although cardiac outputs are generally not affected.
On ECG, QRS widening, and prolonged PR & QT intervals can be seen. The QRS complex and T wave may occasionally show some slight decreases in voltage.
Uses/Indications - Procainamide is indicated for the treatment of ventricular premature complexes (VPC’s), ventricular tachycardia, or supraventricular tachycardia associated with Wolff-Parkinson-White (WPW) syndrome with wide QRS complexes. Higher doses may be beneficial in the treatment of supraventricular tachycardias, although procainamide cannot be considered a first-line agent for this dysrhythmia.
Pharmacokinetics - After IM or IV administration, the onset of action is practically immediate. After oral administration in humans, approximately 75-95% of a dose is absorbed in the intestine, but some patients absorb less than 50% of a dose. Food, delayed gastric emptying or decreased stomach pH may delay oral absorption. In dogs, it has been reported that the oral bioavailability is approximately 85% and the absorption half-life is 0.5 hours. However, there is an apparent large degree of variability in both bioavailability and half-life of absorption.
Distribution of procainamide is highest into the CSF, liver, spleen, kidneys, lungs, heart and muscles. The volume of distribution in dogs is approximately 1.4 - 3 L/kg. It is only approximately 20% protein bound in humans and 15% in dogs. Procainamide can cross the placenta and is excreted into milk.
The elimination half-life in dogs has been reported to be variable, most studies report values between 2-3 hours. In humans, procainamide is metabolized to N-acetyl-procainamide (NAPA), an active metabolite. It appears, however, that dogs do not form appreciable amounts of NAPA from procainamide. In the dog, approximately 90% (50-70% unchanged) of an intravenous dose is excreted in the urine as procainamide and metabolites within 24 hours after dosing.
Contraindications/Precautions - Procainamide may be contraindicated in patients with myasthenia gravis (see Drug Interactions). Procainamide is contraindicated in patients hypersensitive to it, procaine or other chemically related drugs. In humans, procainamide is contraindicated in patients with systemic lupus erythematosis (SLE), but it is unknown if it adversely affects dogs with this condition. Procainamide should not be used in patients with torsade de pointes, or with 2nd or 3rd degree heart block (unless artificially paced).
Procainamide should be used with extreme caution, if at all, in patients with cardiac glycoside intoxication. It should be used with caution in patients with significant hepatic or renal disease or with congestive heart failure.
Adverse Effects/Warnings - Adverse effects are generally dosage (blood level) related in the dog. Gastrointestinal effects may include anorexia, vomiting, or diarrhea. Effects related to the cardiovascular system can include weakness, hypotension, negative inotropism, widened QRS complex and QT intervals, AV block, multiform ventricular tachycardias. Fevers and leukopenias are a possibility. Profound hypotension can occur if injected too rapidly IV. In humans, an SLE syndrome can occur, but its incidence has not been established in the dog. Dosages should usually be reduced in patients with renal failure, congestive heart failure or those who are critically ill.
Overdosage - Symptoms of overdosage can include hypotension, lethargy, confusion, nausea, vomiting, and oliguria. Cardiac signs may include widening of the QRS complex, junctional tachycardia, ventricular fibrillation, or intraventricular conduction delays.
If an oral ingestion, emptying of the gut and charcoal administration may be beneficial to remove any unabsorbed drug. IV fluids, plus dopamine, phenylephrine, or norepinephrine could be considered to treat hypotensive effects. A 1/6 molar intravenous infusion of sodium lactate may be used in an attempt to reduce the cardiotoxic effects of procainamide. Forced diuresis using fluids and diuretics along with reduction of urinary pH, can enhance the renal excretion of the drug. Temporary cardiac pacing may be necessary should severe AV block occur.
Drug Interactions - Use with caution with other antidysrhythmic agents, as additive cardiotoxic or other toxic effects may result. Procainamide may antagonize the effects of pyridostigmine, neostigmine, or other anticholinesterases in patients with myasthenia gravis.
Procainamide may potentiate the effects of other drugs having hypotensive effects.
Procainamide should only be used in patients with digitalis intoxication when treatment with potassium, lidocaine or phenytoin is ineffective. Cimetidine may decrease the renal clearance of procainamide with a resultant increase in serum level of procainamide. Procainamide may potentiate or prolong the neuromuscular blocking activity of muscle relaxants such as succinylcholine or other agents (e.g., aminoglycosides) having neuromuscular blocking activity.
a) Intravenous: 0.5 mg/kg every 10 minutes until resolution or until a total of 2 - 4 mg/kg has been given. (Muir and McGuirk 1987a)
Monitoring Parameters -
1) ECG; continuously with IV dosing
2) Blood pressure if possible, during IV administration
3) Symptoms of toxicity (see Adverse Reactions/Overdosage)
4) Serum levels
Because of the variability in pharmacokinetics reported in the dog, it is encouraged to monitor therapy using serum drug levels. Because dogs apparently do not form the active metabolite NAPA in appreciable quantities, the therapeutic range for procainamide is controversial. Therapeutic ranges from 3 - 8 micrograms/ml to 8 - 20 micrograms/ml have been suggested. This author would suggest using the lower range as a guideline to initiate therapy, but not to hesitate increasing doses to attain the higher values if efficacy is not achieved and toxicity is not a problem. Digitalis-induced ventricular arrhythmias may require substantially higher blood levels for control. Trough levels are usually specified when monitoring oral therapy. Because NAPA is routinely monitored with procainamide in human medicine, it may be necessary to request to your laboratory that NAPA values need not be automatically run for canine patients.
Client Information - Oral products should be administered at evenly spaced intervals throughout the day/night. Unless otherwise directed, give the medication on an empty stomach at least 1/2 hour before feeding. Notify veterinarian if animal’s condition deteriorates or symptoms of toxicity (e.g., vomiting, diarrhea, weakness, etc.) occur.
Dosage Forms/Preparations/FDA Approval Status/Withholding Times -
Veterinary-Approved Products: None
Procainamide HCl for injection 100 mg/ml in 10 ml vials & 500 mg/ml in 2 ml vials and 2 & 4 ml syringes; Pronestyl® (Princeton Pharm.); Generic; (Rx)
Procainamide HCl Tablets or Capsules 250 mg, 375 mg, 500 mg; Pronestyl® (Princeton Pharm.); Generic; (Rx)
Procainamide HCl Sustained-Release Tablets 250 mg, 500 mg, 1000 mg (Extended release only) (Note: These products are not recommended for initial therapy and have not been extensively used in veterinary medicine.); Pronestyl® SR ( Princeton Pharm.), Procanbid® (Parke-Davis), Generic; (Rx)
Forest) (Rx); Predcor-50® (Hauck) (Rx); generic
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