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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Medication Safety Issues
Sound-alike/look-alike issues:
Procanbid may be confused with probenecid, Procan SR®
Procan SR® may be confused with procanbid
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.
Procainamide hydrochloride is available in 10 mL vials of 100 mg/mL and in 2 mL vials with 500 mg/mL. Note that BOTH vials contain 1 gram of drug; confusing the strengths can lead to massive overdoses or underdoses.
PCA is an error-prone abbreviation (mistaken as patient controlled analgesia)
Pronunciation
(pro KANE a mide)
Index Terms
Generic Available
Yes
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Intravenous: Treatment of ventricular arrhythmias (eg, sustained ventricular tachycardia [VT]); Note: Due to proarrhythmic effects, use should be reserved for life-threatening arrhythmias
Oral (Canadian labeling; not available in U.S.): Treatment of supraventricular arrhythmias. Note: In the treatment of atrial fibrillation, use only when preferred treatment is ineffective or cannot be used. Use in paroxysmal atrial tachycardia when reflex stimulation or other measures are ineffective.
Use: Unlabeled/Investigational
Paroxysmal supraventricular tachycardia (PSVT); prevent recurrence of ventricular tachycardia; symptomatic premature ventricular contractions
ACLS guidelines: I.V.: Treatment of the following arrhythmias in patients with preserved left ventricular function: Stable monomorphic VT; atrial fibrillation or atrial flutter, including pre-excitation syndrome; AV re-entrant narrow complex tachycardias (eg, re-entrant SVT), uncontrolled by adenosine and vagal maneuvers; and stable wide complex regular tachycardia (likely VT)
PALS guidelines: I.V.: Tachycardia with pulses and poor perfusion (probable SVT [unresponsive to vagal maneuvers and adenosine or synchronized cardioversion]; probable VT [unresponsive to synchronized cardioversion or adenosine])
Pregnancy Risk Factor
C
Lactation
Enters breast milk/not recommended
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 procainamide, procaine, other ester-type local anesthetics, or any component of the formulation; complete heart block; second-degree AV block or various types of hemiblock (without a functional artificial pacemaker); SLE; torsade de pointes
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 (eg, agranulocytosis) have occurred with therapeutic doses; weekly monitoring is recommended during the first 3 months of therapy and periodically thereafter. Discontinue procainamide if this occurs.
• 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 rising ANA titers or with SLE symptoms and choose an alternative agent.
• 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 due to negative inotropic actions.
• 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; may exacerbate or increase the risk of conduction disturbances.
Dosage form specific issues:
• Sodium metabisulfite: This product contains sodium metabisulfite which may cause allergic-type reactions, including anaphylactic symptoms and life-threatening asthmatic episodes in susceptible people; this is seen more frequently in asthmatics.
Special populations:
• Elderly: Use caution and dose cautiously; renal clearance of procainamide/NAPA declines in patients ?50 years of age (independent of creatinine clearance reductions) and in the presence of concomitant renal impairment.
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, non-life-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. Procainamide should be reserved for patients with life-threatening ventricular arrhythmias.
Adverse Reactions
>1%:
Cardiovascular: Hypotension (I.V. up to 5%)
Dermatologic: Rash
Gastrointestinal: Diarrhea (oral: 3% to 4%), nausea (oral: 3% to 4%), taste disorder (oral: 3% to 4%), vomiting (oral: 3% to 4%)
Miscellaneous: Positive ANA (?50%), SLE-like syndrome (?30%, increased incidence with long-term therapy or slow acetylators; syndrome may include abdominal pain, arthralgia, arthritis, chills, fever, hepatomegaly, myalgia, pericarditis, pleural effusion, pulmonary infiltrates, rash)
<1% (Limited to important or life-threatening): Agranulocytosis, alkaline phosphatase increased, angioedema, anorexia, aplastic anemia, arrhythmia exacerbated, arthralgia, asystole, bone marrow suppression, confusion, disorientation, dizziness, drug fever, fever, first degree heart block, flushing, granulomatous hepatitis, hallucinations, hemolytic anemia, hepatic failure, hyperbilirubinemia, hypoplastic anemia, intrahepatic cholestasis, leukopenia, lightheadedness, maculopapular rash, mental depression, myasthenia gravis worsened, myocardial contractility depressed, myopathy, neuromuscular blockade, neutropenia, pancytopenia, paradoxical increase in ventricular rate in atrial fibrillation/flutter, peripheral/polyneuropathy, pleural effusion, positive Coombs' test, proarrhythmia, psychosis, QTc-interval prolongation, pruritus, rash, second-degree heart block, tachycardia, thrombocytopenia, torsade de pointes, transaminases increased, urticaria, ventricular fibrillation, weakness
Postmarketing and/or case reports: Cerebellar ataxia, demyelinating polyradiculoneuropathy, mania, myocarditis, pancreatitis, pseudo-obstruction, pulmonary embolism, respiratory failure due to myopathy, vasculitis
Metabolism/Transport Effects
Substrate of CYP2D6 (major)
Drug Interactions
Alfuzosin: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
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
Artemether: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Chloroquine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk C: Monitor therapy
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
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Dronedarone: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
Gadobutrol: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk D: Consider therapy modification
Lumefantrine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Neuromuscular-Blocking Agents: Procainamide may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nilotinib: May enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Risk C: Monitor therapy
Pimozide: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Pimozide. 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
QuiNINE: QTc-Prolonging Agents may enhance the QTc-prolonging effect of QuiNINE. QuiNINE may enhance the QTc-prolonging effect of QTc-Prolonging Agents. Risk X: Avoid combination
Ranitidine: May increase the serum concentration of Procainamide. Ranitidine may also increase the concentration of the active N-acetyl-procainamide (NAPA) metabolite. Risk C: Monitor therapy
Tetrabenazine: QTc-Prolonging Agents may enhance the QTc-prolonging effect of Tetrabenazine. Risk X: Avoid combination
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
Store undiluted vials at room temperature of 15°C to 30°C (59°F to 86°F). The solution is initially colorless but may turn slightly yellow on standing. Injection of air into the vial causes solution to darken. Discard solutions darker than light amber. Color formation may occur upon refrigeration. When admixed in NS or D5W to a final concentration of 2-4 mg/mL, solution is stable at room temperature for 24 hours and for 7 days under refrigeration.
Reconstitution
Maximum concentration (loading dose only): 20 mg/mL
Maximum admixture concentration: 8 mg/mL
Usual admixture concentration: 1 g/250 mL NS/D5W or 1 g/500 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 (Raymond, 1988).
Compatibility
Stable in 1/2NS, NS, sterile water for injection; variable stability (consult detailed reference) in D5NS, D5W.
Y-site administration: Compatible: Amiodarone, bivalirudin, cisatracurium, dexmedetomidine, famotidine, fenoldopam, heparin, hetastarch in lactated electrolyte injection (Hextend®), hydrocortisone sodium succinate, nitroprusside, pantoprazole, potassium chloride, ranitidine, remifentanil, vasopressin, vitamin B complex with C. Incompatible: Lansoprazole, milrinone. Variable (consult detailed reference): Diltiazem, inamrinone, nesiritide.
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; decreased with congestive heart failure or shock
Protein binding: 15% to 20%
Metabolism: Hepatic via acetylation to produce N-acetyl procainamide (NAPA) (active metabolite)
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: I.M.: 15-60 minutes
Excretion: Urine (30% to 60% unchanged procainamide; 6% to 52% as NAPA); feces (<5% unchanged procainamide. Note: >80% of formed NAPA is renally eliminated in contrast to procainamide which is ~50% renally eliminated (Gibson, 1977).
Dosage
Must be titrated to patient's response
Children:
I.M.: 50 mg/kg/24 hours divided into doses of 1/8 to 1/4 every 3-6 hours in divided doses
I.V.:
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:
I.M.: 0.5-1 g every 4-8 hours
I.V.:
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 20-50 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. Note: Not recommended for use in ongoing ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) due to prolonged administration time and uncertain efficacy.
Oral (not available in the U.S.; Canadian labeling): Sustained release formulation (Procan SR®): Maintenance: 50 mg/kg/24 hours given in divided doses every 6 hours
Suggested Procan SR® maintenance dose:
<55 kg: 500 mg every 6 hours
55-91 kg: 750 mg every 6 hours
>91 kg: 1000 mg every 6 hours
Elderly: Initiate doses at lower end of dosage range.
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%): Monitor procainamide/N-acetylprocainamide (NAPA) levels; supplementation may be necessary.
NAPA: Not dialyzable (0% to 5%)
Procainamide/NAPA: Not peritoneal dialyzable (0% to 5%)
Procainamide/NAPA: 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 sustained release drug products (not available in the U.S.).
Administration: I.V.
Must dilute prior to I.V. administration. Loading dose: Maximum rate: 50 mg/minute
Administration: I.V. Detail
pH: 4-6
Monitoring Parameters
ECG, blood pressure, renal function; with prolonged use monitor CBC with differential, platelet count; procainamide and NAPA blood levels in patients with hepatic impairment, renal impairment, or receiving constant infusion >3 mg/minute for longer than 24 hours; ANA titers
Reference Range
Timing of serum samples: 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
Test Interactions
In the presence of propranolol or suprapharmacologic concentrations of lidocaine or meprobamate, tests which depend on fluorescence to measure procainamide/NAPA concentrations may be affected.
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 (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
Clinical Pearls/Comments: 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, mepivacaine and levonordefrin [Carbocaine® 2% with Neo-Cobefrin®]) be used with caution.
Dental Comment
Procainamide is known to prolong the QT interval. The QT interval is measured as the time and distance between the Q point of the QRS complex and the end of the T wave in the ECG tracing. After adjustment for heart rate, the QT interval is defined as prolonged if it is more than 450 msec in men and 460 msec in women. A long QT syndrome was first described in the 1950s and 60s as a congenital syndrome involving QT interval prolongation and syncope and sudden death. Some of the congenital long QT syndromes were characterized by a peculiar electrocardiographic appearance of the QRS complex involving a premature atria beat followed by a pause, then a subsequent sinus beat showing marked QT prolongation and deformity. This type of cardiac arrhythmia was originally termed “torsade de pointes” (translated from the French as “twisting of the points”). Procainamide is considered as having a risk of causing torsade de pointes. Since 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, a medical consult is suggested.
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. [CAN] = Canadian brand name
Injection, solution, as hydrochloride: 100 mg/mL (10 mL); 500 mg/mL (2 mL) [contains sodium metabisulfite]
Tablet, sustained release, oral, as hydrochloride:
Procan SR® [CAN]: 250 mg, 500 mg, 750 mg [not available in U.S.]
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.
Gibson TP, Atkinson AJ Jr, Matusik E, et al, “Kinetics of Procainamide and N-Acetylprocainamide in Renal Failure,” Kidney Int, 1977, 12(6):422-9
Raymond GG, Reed MT, Teagarden JR, et al, “Stability of Procainamide Hydrochloride in Neutralized 5% Dextrose Injection,” Am J Hosp Pharm, 1988, 45(12):2513-7.
International Brand Names
Lexi-Comp.com
Last full review/revision September 2009
Content last modified September 2009
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