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standards of non-Merck sources.
ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section and/or refer to product labeling for additional detail.
Medication Safety Issues
Sound-alike/look-alike issues:
Procanbid® may be confused with probenecid
Pronestyl® may be confused with Ponstel®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
PCA is an error-prone abbreviation (mistaken as patient controlled analgesia)
Pronunciation
(pro KANE a mide)
U.S. Brand Names
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of ventricular tachycardia (VT), premature ventricular contractions, paroxysmal atrial tachycardia (PSVT), and atrial fibrillation (AF); prevent recurrence of ventricular tachycardia, paroxysmal supraventricular tachycardia, atrial fibrillation or flutter
Use: Unlabeled/Investigational
ACLS guidelines:
Stable monomorphic VT (EF >40%, no CHF)
Stable wide complex tachycardia, likely VT (EF >40%, no CHF, patient stable)
Atrial fibrillation or flutter, including pre-excitation syndrome (EF >40%, no CHF)
AV reentrant, narrow complex tachycardia (eg, reentrant SVT) [preserved ventricular function]
PALS guidelines: Tachycardia with pulses and poor perfusion (possible VT)
Pregnancy Risk Factor
C
Lactation
Enters breast milk/use caution (AAP rates “compatible”)
Breast-Feeding Considerations
Considered compatible by the AAP. However, the AAP stated concern regarding long-term effects and potential for infant toxicity. Use caution and monitor closely if continuing to breast-feed while taking procainamide.
Contraindications
Hypersensitivity to procaine, other ester-type local anesthetics, or any component of the formulation; 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; QT prolongation
Warnings/Precautions
Boxed warnings:
• Blood dyscrasias: See “Other warnings/precautions” below.
• CAST trial: See “Other warnings/precautions” below.
• Drug-induced lupus erythematosus-like syndrome: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Blood dyscrasias: [U.S. Boxed Warning]: Potentially fatal blood dyscrasias have occurred with therapeutic doses; close monitoring is recommended during the first 3 months of therapy.
• Conduction disturbances: Reduce dose if first-degree heart block occurs.
• Drug-induced lupus erythematosus-like syndrome: [U.S. Boxed Warning]: 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.
• Hypersensitivity reaction: With use, hypersensitivity reactions can occur.
• Proarrhythmic effects: Watch for proarrhythmic effects; monitor and adjust dose to prevent QTc prolongation.
Disease-related concerns:
• Atrial fibrillation/flutter: May increase ventricular response rate in patients with atrial fibrillation or flutter; control AV conduction before initiating.
• Electrolyte imbalance: Correct electrolyte disturbances, especially hypokalemia or hypomagnesemia, prior to use and throughout therapy.
• Heart failure (HF): Use with caution in patients with HF; may precipitate or exacerbate condition.
• Myasthenia gravis: Avoid use in myasthenia gravis; may worsen condition.
• Renal impairment: Use with caution in patients with renal impairment; dosage reduction recommended.
Concurrent drug therapy issues:
• Antiarrhythmics: Use caution with concurrent use of other antiarrhythmics.
Dosage form specific issues:
• Bisulfite: Injection may contain bisulfite (allergens).
• Tartrazine: Some tablets contain tartrazine.
Other warnings/precautions:
• CAST trial: [U.S. Boxed Warning] In the Cardiac Arrhythmia Suppression Trial (CAST), recent (>6 days but <2 years ago) myocardial infarction patients with asymptomatic, nonlife-threatening ventricular arrhythmias did not benefit and may have been harmed by attempts to suppress the arrhythmia with flecainide or encainide. An increased mortality or nonfatal cardiac arrest rate (7.7%) was seen in the active treatment group compared with patients in the placebo group (3%). The applicability of the CAST results to other populations is unknown. Antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
Adverse Reactions
>1%:
Cardiovascular: Hypotension (I.V. up to 5%)
Dermatologic: Rash
Gastrointestinal: Diarrhea (3% to 4%), nausea, vomiting, taste disorder, GI complaints (3% to 4%)
<1% (Limited to important or life-threatening): New or worsened arrhythmia (proarrhythmic effect), tachycardia, QT prolongation (excessive), second-degree heart block, torsade de pointes, ventricular arrhythmia, 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, transaminases increased, alkaline phosphatase increased, 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 and includes abdominal pain, arthralgia, pleural effusion, pericarditis, fever, chills, myalgia, rash); positive ANA
Postmarketing and/or case reports: Pancreatitis, pseudo-obstruction, tremor, mania, myocarditis, vasculitis, psychosis, cerebellar ataxia, demyelinating polyradiculoneuropathy, respiratory failure due to myopathy, pulmonary embolism, myopathy
Metabolism/Transport Effects
Substrate of CYP2D6 (major)
Drug Interactions
Amiodarone: Antiarrhythmic Agents (Class Ia) may enhance the QTc-prolonging effect of Amiodarone. Amiodarone may increase the metabolism of Antiarrhythmic Agents (Class Ia). Risk D: Consider therapy modification
Cimetidine: May decrease the excretion of Procainamide. Risk D: Consider therapy modification
Ciprofloxacin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Risk D: Consider therapy modification
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
QTc-Prolonging Agents: May enhance the adverse/toxic effect of other QTc-Prolonging Agents. Their effects can be additive, causing life-threatening ventricular arrhythmias. Risk D: Consider therapy modification
Thioridazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Trimethoprim: May decrease the excretion of Procainamide. Risk D: Consider therapy modification
Ziprasidone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Ziprasidone. The risk of a severe arrhythmia may be increased. Risk X: Avoid combination
Ethanol/Nutrition/Herb Interactions
Ethanol: Avoid ethanol (acute ethanol administration reduces procainamide serum concentrations).
Herb/Nutraceutical: Avoid ephedra (may worsen arrhythmia).
Storage
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.
Reconstitution
Minimum volume: 1 g/250 mL NS/D5W .
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.
Compatibility
Stable in 1/2NS, NS, sterile water for injection; variable stability (consult detailed reference) in D5NS, D5W.
Y-site administration: Compatible: Amiodarone, cisatracurium, famotidine, heparin, hydrocortisone sodium succinate, potassium chloride, ranitidine, remifentanil, vitamin B complex with C. Incompatible Milrinone. Variable (consult detailed reference): Diltiazem, inamrinone.
Compatibility when admixed: Compatible: Amiodarone, atracurium, dobutamine, flumazenil, lidocaine, verapamil. Incompatible: Esmolol, ethacrynate, milrinone, phenytoin. Variable (consult detailed reference): Bretylium.
Mechanism of Action
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
Pharmacodynamics/Kinetics
Onset of action: I.M. 10-30 minutes
Distribution: Vd: Children: 2.2 L/kg; Adults: 2 L/kg; Congestive heart failure or shock: Decreased Vd
Protein binding: 15% to 20%
Metabolism: Hepatic via acetylation to produce N-acetyl procainamide (NAPA) (active metabolite)
Bioavailability: Oral: 75% to 95%
Half-life elimination:
Procainamide (hepatic acetylator, phenotype, cardiac and renal function dependent):
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: Capsule: 45 minutes to 2.5 hours; I.M.: 15-60 minutes
Excretion: Urine (25% as NAPA)
Dosage
Must be titrated to patient's response
Children:
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
Possible VT (pulses and poor perfusion) [PALS 2005 Guidelines]: I.V.; I.O.: 15 mg/kg over 30-60 minutes
Adults:
Oral: Usual dose: 50 mg/kg/24 hours: maximum: 5 g/24 hours (Note: Twice-daily dosing approved for Procanbid®.)
Immediate release formulation: 250-500 mg/dose every 3-6 hours
Extended release formulation: 500 mg to 1 g every 6 hours; Procanbid®: 1000-2500 mg every 12 hours
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. Reduce loading dose to 12 mg/kg in severe renal or cardiac impairment.
Maintenance dose: 1-4 mg/minute by continuous infusion. Maintenance infusions should be reduced by one-third in patients with moderate renal or cardiac impairment and by two-thirds in patients with severe renal or cardiac impairment.
ACLS guidelines: 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:
Oral:
Clcr 10-50 mL/minute: Administer every 6-12 hours.
Clcr <10 mL/minute: Administer every 8-24 hours.
I.V.:
Loading dose: Reduce dose to 12 mg/kg in severe renal impairment.
Maintenance infusion: Reduce dose by one-third in patients with mild renal impairment. Reduce dose by two-thirds in patients with severe renal impairment.
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
Dosing adjustment in hepatic impairment: Reduce dose by 50%.
Administration: Oral
Do not crush or chew extended release drug products.
Administration: I.V.
Must dilute prior to I.V. administration; maximum rate: 50 mg/minute; give around-the-clock to promote less variation in peak and trough serum levels.
Infusion rate: 2 g/250 mL (I.V. infusion requires use of an infusion pump):
1 mg/minute: 7.5 mL/hour
2 mg/minute: 15 mL/hour
3 mg/minute: 22.5 mL/hour
4 mg/minute: 30 mL/hour
5 mg/minute: 37.5 mL/hour
6 mg/minute: 45 mL/hour
Administration: I.V. Detail
pH: 4-6
Monitoring Parameters
ECG, blood pressure, CBC with differential, platelet count; cardiac monitor and blood pressure monitor required during I.V. administration; blood levels in patients with renal failure or receiving constant infusion >3 mg/minute for longer than 24 hours
Reference Range
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 mcg/mL; NAPA 15-25 mcg/mL; Combined: 10-30 mcg/mL
Toxic concentration: Procainamide: >10-12 mcg/mL
Dietary Considerations
Should be taken with water on an empty stomach.
Patient Education
Oral: Take exactly as directed; do not take additional doses or discontinue without consulting prescriber. Avoid alcohol. 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 (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; shortness of breath; acute diarrhea; or unusual fatigue and tiredness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
Monitor closely since clearance is reduced in those >60 years of age. If clinically possible, start doses at lowest recommended dose. Also, elderly frequently have drug therapy which may interfere with the use of procainamide. Adjust dose for renal function in the elderly.
Anesthesia and Critical Care Concerns/Other Considerations
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 (eg, digoxin, beta-blocker, calcium channel blocker) prior to cardioversion to inhibit procainamide-induced increases in ventricular response. Patients should be monitored (ECG and BP) in a controlled setting when initiating therapy.
Cardiovascular Considerations
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 (ECG) in a controlled setting when initiating therapy. Therapy should be discontinued or the dose reduced if the QT interval increases ?25% from baseline.
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Taste disorder.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
Procainamide is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, levonordefrin [Neo-Cobefrin®]) be used with caution.
Mental Health: Effects on Mental Status
May cause dizziness, confusion, depression, or hallucinations
Mental Health: Effects on Psychiatric Treatment
Contraindicated with ziprasidone. May rarely cause agranulocytosis; use caution with clozapine and carbamazepine. Concurrent use with phenothiazines, TCAs, or beta-blockers may produce AV block.
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. I.V. requires use of infusion pump and continuous cardiac and hemodynamic monitoring. Assess results of laboratory tests, therapeutic effectiveness, and adverse reactions at beginning of therapy, when titrating dosage, and on a regular basis with long-term therapy. Note: Procainamide has a low TI and overdose may easily produce severe and life-threatening reactions. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, as hydrochloride: 250 mg, 500 mg [DSC]
Injection, solution, as hydrochloride: 100 mg/mL (10 mL); 500 mg/mL (2 mL) [contains sodium metabisulfite]
Tablet, extended release, as hydrochloride: 500 mg, 750 mg, 1000 mg [DSC]
Procanbid®: 500 mg, 1000 mg [DSC]
Pricing: U.S. (www.drugstore.com)
Capsules (Procainamide HCl)
250 mg (60): $37.99
500 mg (100): $79.99
Capsules (Pronestyl)
250 mg (120): $88.99
Tablet, 12-hour (Procanbid)
500 mg (60): $70.63
Extemporaneously Prepared
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
A suspension of 50 mg/mL can be made with the capsules, distilled water, and a 2:1 simple syrup/cherry syrup mixture; stability 2 weeks under refrigeration (ASHP, 1987)
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.
References
“2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2005, 112(24 Suppl): 1-211.
Buxton AE, Lee KL, Fisher JD, et al, “A Randomized Study of the Prevention of Sudden Death in Patients With Coronary Artery Disease. Multicenter Unsustained Tachycardia Trial Investigators,” N Engl J Med, 1999, 341:1882-90.
Coyle JD and Lima JJ, “Procainamide” in Applied Pharmacokinetics: Principles of Therapeutic Drug Monitoring, 3rd Ed. Evans WE, Schentag JJ, and Jusko W (eds). Applied Therapeutics, Inc: Spokane, WA, 1992, 22-1-33.
Flaker GC, Blackshear JL, McBride R, et al, “Antiarrhythmic Drug Therapy and Cardiac Mortality in Atrial Fibrillation. The Stroke Prevention in Atrial Fibrillation Investigators,” J Am Coll Cardiol, 1992, 20:527-32.
Morganroth J and Goin JE, “Quinidine-Related Mortality n the Short-to-Medium Term Treatment of Ventricular Arrhythmias. A Meta-analysis,” Circulation, 1991, 84(5):1977-83.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2008
Content last modified August 2008
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