Yes

Antiarrhythmic Agent, Class I-A

Treatment of ventricular tachycardia, premature ventricular contractions, paroxysmal atrial tachycardia, and atrial fibrillation; prevent recurrence of ventricular tachycardia, paroxysmal supraventricular tachycardia, atrial fibrillation or flutter

C

Hypersensitivity to procain or other ester-type local anesthetics; complete heart block (except in patients with a functioning artificial pacemaker); second-degree AV block (without a functional pacemaker); various types of hemiblock (without a functional pacemaker); SLE; torsade de pointes; concurrent cisapride use

Monitor and adjust dose to prevent QTc prolongation. Watch for proarrhythmic effects. May precipitate or exacerbate CHF. Reduce dosage in renal impairment. May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating. Correct hypokalemia before initiating therapy. Hypokalemia may worsen toxicity. Use caution in digoxin-induced toxicity (can further depress AV conduction). Reduce dose if first-degree heart block occurs. Use caution with concurrent use of other antiarrhythmics. Avoid use in myasthenia gravis (may worsen condition). Hypersensitivity reactions can occur. Some tablets contain tartrazine; injection may contain bisulfite (allergens).

Long-term administration leads to the development of a positive antinuclear antibody (ANA) test in 50% of patients which may result in a drug-induced lupus erythematosus-like syndrome (in 20% to 30% of patients); discontinue procainamide with SLE symptoms and choose an alternative agent

>1%:

Dermatologic: Rash

Gastrointestinal: Diarrhea (3% to 4%), nausea, vomiting, taste disorder, GI complaints (3% to 4%)

<1% (Limited to important or life-threatening symptoms): New or worsened arrhythmias (proarrhythmic effect), tachycardia, QT prolongation (excessive), hypotension, second-degree heart block, torsade de pointes, ventricular arrhythmias, depressed myocardial contractility, paradoxical increase in ventricular rate in atrial fibrillation/flutter, dizziness, lightheadedness, confusion, hallucinations, mental depression, disorientation, fever, drug fever, rash, urticaria, pruritus, angioneurotic edema, flushing, maculopapular rash, hemolytic anemia, agranulocytosis, neutropenia, thrombocytopenia (0.5%), positive Coombs' test, bone marrow suppression, hypoplastic anemia,leukopenia, pancytopenia, aplastic anemia,elevated transaminases, increased alkaline phosphatase, hyperbilirubinemia, hepatic failure,granulomatous hepatitis, intrahepatic cholestasis, arthralgia, myalgia (<0.5%), worsening of myasthenia gravis, neuromuscular blockade, weakness, peripheral/polyneuropathy, myopathy, pleural effusion, SLE-like syndrome (increased incidence with long-term therapy: arthralgia, pleural pain, abdominal pain, arthralgia, pleural effusion, pericarditis, fever, chills, myalgia, rash); positive ANA

Case reports: Pancreatitis, pseudo-obstruction, tremor, mania, myocarditis, vasculitis, psychosis, cerebellar ataxia, demyelinating polyradiculoneuropathy, respiratory failure due to myopathy, pulmonary embolism, myopathy

Has a low toxic:therapeutic ratio and may easily produce fatal intoxication (acute toxic dose: 5 g in adults); symptoms of overdose include sinus bradycardia, sinus node arrest or asystole, P-R, QRS or Q-T interval prolongation, torsade de pointes (polymorphous ventricular tachycardia) and depressed myocardial contractility, which along with alpha-adrenergic or ganglionic blockade, may result in hypotension and pulmonary edema; other effects are seizures, coma, and respiratory arrest.

Treatment is primarily symptomatic and effects usually respond to conventional therapies (fluids, positioning, vasopressors, anticonvulsants, antiarrhythmics). Note: Do not use other type 1a or 1c antiarrhythmic agents to treat ventricular tachycardia; sodium bicarbonate may treat wide QRS intervals or hypotension; markedly impaired conduction or high degree A-V block, unresponsive to bicarbonate, indicates consideration of a pacemaker is needed.

Amiodarone increases procainamide and NAPA blood levels; consider reducing procainamide dosage by 25% with concurrent use.

Cimetidine increases procainamide and NAPA blood concentrations; monitor blood levels closely or use an alternative H₂ antagonist.

Cisapride and procainamide may increase the risk of malignant arrhythmia; concurrent use is contraindicated.

Neuromuscular blocking agents: Procainamide may potentiate neuromuscular blockade.

Ofloxacin may increase procainamide levels due to an inhibition of renal secretion; monitor levels for procainamide closely.

Drugs which may prolong the QT interval include amiodarone, amitriptyline, astemizole, bepridil, disopyramide, erythromycin, haloperidol, imipramine, pimozide, quinidine, sotalol, and thioridazine. Effects/toxicity may be increased; use with caution.

Sparfloxacin, gatifloxacin, and moxifloxacin may result in additional prolongation of the QT interval; concurrent use is contraindicated.

Trimethoprim increases procainamide and NAPA blood levels; closely monitor levels.

Procainamide may be stored at room temperature up to 27°C; however, refrigeration retards oxidation, which causes color formation. The solution is initially colorless but may turn slightly yellow on standing. Injection of air into the vial causes the solution to darken. Solutions darker than a light amber should be discarded.

Stability of admixture at room temperature in D₅W or NS: 24 hours

Some information indicates that procainamide may be subject to greater decomposition in D₅W unless the admixture is refrigerated or the pH is adjusted. Procainamide is believed to form an association complex with dextrose - the bioavailability of procainamide in this complex is not known and the complex formation is reversible.

Decreases myocardial excitability and conduction velocity and may depress myocardial contractility, by increasing the electrical stimulation threshold of ventricle, HIS-Purkinje system and through direct cardiac effects

Onset of action: I.M. 10-30 minutes

Distribution: V_d: Children: 2.2 L/kg; Adults: 2 L/kg; Congestive heart failure of shock: Decreased V_d

Protein binding: 15% to 20%

Metabolism: By acetylation in the liver to produce N-acetyl procainamide (NAPA) (active metabolite)

Bioavailability: Oral: 75% to 95%

Half-life:

Procainamide: (Dependent upon hepatic acetylator, phenotype, cardiac function, and renal function):

Children: 1.7 hours

Adults: 2.5-4.7 hours

Anephric: 11 hours

NAPA: (Dependent upon renal function):

Children: 6 hours

Adults: 6-8 hours

Anephric: 42 hours

Time to peak serum concentration: Capsule: Within 45 minutes to 2.5 hours; I.M.: 15-60 minutes

Elimination: Urinary excretion (25% as NAPA)

Must be titrated to patient's response

Oral: 15-50 mg/kg/24 hours divided every 3-6 hours

I.M.: 50 mg/kg/24 hours divided into doses of 1/8 to 1/4 every 3-6 hours in divided doses until oral therapy is possible

I.V. (infusion requires use of an infusion pump):

Load: 3-6 mg/kg/dose over 5 minutes not to exceed 100 mg/dose; may repeat every 5-10 minutes to maximum of 15 mg/kg/load

Maintenance as continuous I.V. infusion: 20-80 mcg/kg/minute; maximum: 2 g/24 hours

Adults:

Oral: 250-500 mg/dose every 3-6 hours or 500 mg to 1 g every 6 hours sustained release; usual dose: 50 mg/kg/24 hours; maximum: 4 g/24 hours ( Note: Twice daily dosing approved for Procanbid™)

I.M.: 0.5-1 g every 4-8 hours until oral therapy is possible

I.V. (infusion requires use of an infusion pump): Loading dose: 15-18 mg/kg administered as slow infusion over 25-30 minutes or 100-200 mg/dose repeated every 5 minutes as needed to a total dose of 1 g; maintenance dose: 1-6 mg/minute by continuous infusion

Infusion rate: 2 g/250 mL D₅W/NS (I.V. infusion requires use of an infusion pump):

1 mg/minute: 7 mL/hour

2 mg/minute: 15 mL/hour

3 mg/minute: 21 mL/hour

4 mg/minute: 30 mL/hour

5 mg/minute: 38 mL/hour

6 mg/minute: 45 mL/hour

Refractory ventricular fibrillation: 30 mg/minute, up to a total of 17 mg/kg; I.V. maintenance infusion: 1-4 mg/minute; monitor levels and do not exceed 3 mg/minute for >24 hours in adults with renal failure.

ACLS guidelines: I.V.: Infuse 20 mg/minute until arrhythmia is controlled, hypotension occurs, QRS complex widens by 50% of its original width, or total of 17 mg/kg is given.

Dosing interval in renal impairment:

Cl_cr 10-50 mL/minute: Administer every 6-12 hours.

Cl_cr <10 mL/minute: Administer every 8-24 hours.

Dialysis:

Procainamide: Moderately hemodialyzable (20% to 50%): 200 mg supplemental dose posthemodialysis is recommended.

N-acetylprocainamide: Not dialyzable (0% to 5%)

Procainamide/N-acetylprocainamide: Not peritoneal dialyzable (0% to 5%)

Procainamide/N-acetylprocainamide: Replace by blood level during continuous arteriovenous or venovenous hemofiltration (CAVH/CAVHD).

Dosing adjustment in hepatic impairment: Reduce dose 50%.

Should be administered with water on an empty stomach

EKG, blood pressure, CBC with differential, platelet count; cardiac monitor and blood pressure monitor required during I.V. administration

Timing of serum samples: Draw trough just before next oral dose; draw 6-12 hours after I.V. infusion has started; half-life is 2.5-5 hours

Therapeutic levels: Procainamide: 4-10 mg/mL; NAPA 15-25 mg/mL; Combined: 10-30 mg/mL

Toxic concentration: Procainamide: >10-12 mg/mL

In patients with pre-existing cardiovascular disease, the incidence of proarrhythmia and mortality may be increased with Class Ia antiarrhythmic agents. Procainamide may be used to pharmacologically convert atrial fibrillation to normal sinus rhythm. In this setting, it is important that AV nodal conduction be controlled (digoxin, beta-blocker, calcium channel blocker) prior to cardioversion to inhibit procainamide-induced increases in ventricular response. Patients should be monitored (EKG) in a controlled setting when initiating therapy. Therapy should be discontinued or the dose reduced if the QT interval increases greater than or equal to 25% from baseline.

May cause dizziness, confusion, depression, or hallucinations

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; concurrent use with phenothiazines, TCAs, or beta-blockers may produce AV block

No information available to require special precautions

No effects or complications reported

Oral: Take exactly as directed; do not take additional doses or discontinue without consulting prescriber. You will need regular cardiac checkups and blood tests while taking this medication. You may experience dizziness, lightheadedness, or visual changes (use caution when driving or engaging in tasks requiring alertness until response to drug is known); loss of appetite (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); headaches (prescriber may recommend mild analgesic); or diarrhea (exercise, yogurt, or boiled milk may help - if persistent consult prescriber). Report chest pain, palpitation, or erratic heartbeat; increased weight or swelling of hands or feet; acute diarrhea; or unusual fatigue and tiredness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Consult prescriber if breast-feeding.

Do not crush sustained release drug product

Capsule, as hydrochloride: 250 mg, 375 mg, 500 mg

Injection, as hydrochloride: 100 mg/mL (10 mL); 500 mg/mL (2 mL)

Tablet, as hydrochloride: 250 mg, 375 mg, 500 mg

Tablet, as hydrochloride, sustained release: 250 mg, 500 mg, 750 mg, 1000 mg

Tablet, as hydrochloride, sustained release (Procanbid™): 500 mg, 1000 mg

Note: Several formulations have been described, some being more complex; for all formulations, the pH must be 4-6 to prevent degradation; some preparations require adjustment of pH; shake well before use

Concentrations of 5, 50, and 100 mg/mL oral liquid preparations, (made with the capsules, sterile water for irrigation and cherry syrup) stored at 4°C to 6°C (pH 6) were stable for at least 6 months (Metras, 1992).

A sucrose-based syrup (procainamide 50 mg/mL) made with capsules, distilled water, simple syrup, parabens, and cherry flavoring had a calculated stability of 456 days at 25°C and measured stability of 42 days at 40°C (pH ~5) while a maltitol-based syrup (procainamide 50 mg/mL) made with capsules, distilled water, Lycasin® (a syrup vehicle with 75% w/w maltitol), parabens, sodium bisulfate, saccharin, sodium acetate, pineapple and apricot flavoring, FD & C yellow number 6, (pH adjusted to 5 with glacial acetic acid) had a calculated stability of 97 days at 25°C and a measured stability of 94 days at 40°C. The maltitol-based syrup was more stable than the sucrose-based syrup when temperature was >37°C, but the sucrose-based syrup was more stable at temperatures <37°C (Alexander, 1993).

Alexander KS, Pudipeddi M, and Parker GA, "Stability of Procainamide Hydrochloride Syrups Compounded From Capsules," Am J Hosp Pharm, 1993, 50(4):693-8.

Handbook in Extemporaneous Formulations, Bethesda, MD: American Society of Hospital Pharmacists, 1987.

Metras JI, Swenson CF, and MacDermott MP, "Stability of Procainamide Hydrochloride in an Extemporaneously Compounded Oral Liquid," Am J Hosp Pharm, 1992, 49(7):1720-4.

Swenson CF, "Importance of Following Instructions When Compounding," Am J Hosp Pharm, 1993, 50(2):261.

Adams LE, Roberts SM, Donovan-Brand R, et al, "Study of Procainamide Hapten-Specific Antibodies in Rabbits and Humans," Int J Immunopharmacol, 1993, 15(8):887-97.

American College of Cardiology, American Heart Association Task Force, "Adult Advanced Cardiac Life Support" and "Pediatric Advanced Life Support Guidelines," JAMA, 1992, 268(16):2199-241 and 2262-75.

Braden GL, Fitzgibbons JP, Germain MJ, et al, "Hemoperfusion for Treatment of N-Acetylprocainamide Intoxication," Ann Intern Med, 1986, 105(1):64-5.

Prendergast MD and Nasca TJ, "Anticholinergic Syndrome With Procainamide Toxicity," JAMA, 1984, 251(22):2926-7.

Rosansky SJ and Brudy ME, "Procainamide Toxicity in a Patient With Acute Renal Failure," Am J Kidney Dis, 1986, 7(6):502-6.

Singh S, Gelband H, Mehta AV, et al, "Procainamide Elimination Kinetics in Pediatric Patients," Clin Pharmacol Ther, 1982, 32(5):607-11.