(pro KANE a mide)
- PCA (error-prone abbreviation)
- Procainamide Hydrochloride
- Procaine Amide Hydrochloride
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as hydrochloride:
Generic: 100 mg/mL (10 mL); 500 mg/mL (2 mL)
- Antiarrhythmic Agent, Class Ia
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
Vd: Children: 2.2 L/kg; Adults: 2 L/kg; decreased with congestive heart failure or shock
Hepatic via acetylation to produce N-acetyl procainamide (NAPA) (active metabolite)
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).
Onset of Action
IM 10 to 30 minutes
Time to Peak
Serum: IM: 15 to 60 minutes
Procainamide (hepatic acetylator, phenotype, cardiac and renal function dependent): Children: 1.7 hours; Adults: 2.5 to 4.7 hours; Anephric: 11 hours
NAPA (renal function dependent): Children: 6 hours; Adults: 6 to 8 hours; Anephric: 42 hours
15% to 20%
Special Populations: Renal Function Impairment
Elimination half-life is prolonged.
Special Populations: Elderly
Elimination half-life is prolonged.
Use: Labeled Indications
Intravenous: Treatment of life-threatening ventricular arrhythmias
Oral [Canadian product]: 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.
Paroxysmal supraventricular tachycardia (PSVT); prevent recurrence of ventricular tachycardia
Treatment of the following arrhythmias in adults with preserved left ventricular function (ACLS): Stable monomorphic VT, pre-excited atrial fibrillation, and stable wide complex regular tachycardia (likely VT)
Treatment of the following arrhythmias in children (PALS): 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])
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
Dose must be individualized and titrated to patient response.
IM: 50 mg/kg/day divided every 3 to 6 hours or 0.5 to 1 g every 4 to 8 hours (Koch-Weser, 1971)
Loading dose: 500 to 600 mg administered as a slow infusion over 25 to 30 minutes or 100 mg/dose at a rate not to exceed 50 mg/minute repeated every 5 minutes as needed to a total dose of 1,000 mg. Discontinue loading dose when arrhythmia is controlled, hypotension occurs, QRS complex widens by 50% of its original width, or total of 600 mg to 1,000 mg is given.
Maintenance infusion: 2 to 6 mg/minute by continuous infusion.
Alternate recommendations (off-label dose): Stable monomorphic ventricular tachycardia:
Loading dose: 20 to 50 mg/minute or 100 mg every 5 minutes until arrhythmia is controlled, hypotension occurs, QRS complex widens by 50% of its original width, or total of 17 mg/kg is given (ACLS [Neumar 2010]). Note: Not recommended for use in ongoing ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) due to prolonged administration time and uncertain efficacy (AHA 2005).
Maintenance infusion: 1 to 4 mg/minute (ACLS [Neumar 2010]; Hazinski 2015).
Oral [Canadian product]: 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 to 91 kg: 750 mg every 6 hours
>91 kg: 1,000 mg every 6 hours
Pre-excited atrial fibrillation (off-label use):
Loading dose: IV: 20 to 50 mg/minute or 100 mg every 5 minutes until arrhythmia is controlled, hypotension occurs, QRS complex widens by 50% of its original width, or total of 17 mg/kg is given (ACLS [Neumar 2010]).
Maintenance infusion: 1 to 4 mg/minute (ACLS [Neumar 2010]; Hazinski 2015).
Refer to adult dosing. Initiate doses at lower end of dosage range.
Dose must be individualized and titrated to patient's response.
Arrhythmias: Limited data available:
IM: Children and Adolescents: 20 to 30 mg/kg/day divided every 4 to 6 hours; maximum daily dose: 4,000 mg/day (Nelson 1996)
IV, I.O.: Infants, Children, and Adolescents:
Loading dose: 10 to 15 mg/kg over 30 to 60 minutes; in adults, maximum dose range: 1,000 to 1,500 mg (Hegenbarth 2008; Kliegman 2011)
Maintenance: Continuous IV infusion: 20 to 80 mcg/kg/minute; maximum daily dose: 2,000 mg/24 hours (Kliegman 2011)
Stable wide-complex tachycardia of unknown origin (atrial or ventricular) or SVT (off-label use): Note: Avoid or use extreme caution when administering procainamide with other drugs that prolong QT interval (eg, amiodarone); consider consulting with cardiology expert.
Infants, Children, and Adolescents: IV, I.O.: Loading dose: 15 mg/kg infused over 30 to 60 minutes; monitor ECG and blood pressure; stop the infusion if hypotension occurs or QRS complex widens by >50% of baseline (PALS [Kleinman 2010]).
Dosing: Renal Impairment
Oral [Canadian product]:
Manufacturer’s labeling: Manufacturer recommends increasing dosing interval; specific interval increase not described
CrCl >50 mL/minute: No dosage adjustment necessary (Bauer 2008)
CrCl 10 to 50 mL/minute: Reduce initial daily dose by 25% to 50% (Bauer 2008)
CrCl <10 mL/minute: Reduce initial daily dose by 50% to 75% (Bauer 2008). Monitor procainamide/NAPA concentrations closely.
Infants, Children, and Adolescents: There are no specific recommendations provided in the manufacturer's labeling; dose must be individualized and titrated to patient's response; monitor serum concentrations; some have suggested the following (Aronoff 2007): Note: Renally adjusted dose recommendations are based on a dose of loading dose of 15 mg/kg total.
GFR <10 mL/minute/1.73 m2:
Loading dose: Reduce dose to 12 mg/kg
Maintenance infusion: Start at lower end of continuous infusion range of 20 to 80 mcg/kg/minute
Manufacturer’s labeling: Manufacturer recommends dosage reduction; specific dosage reduction not described, however, close monitoring of procainamide and NAPA concentrations and clinical effectiveness recommended
CrCl >50 mL/minute: No dosage adjustment necessary (Bauer 2008)
CrCl 10–50 mL/minute: Reduce continuous infusion dose by 25% to 50% (Bauer 2008)
CrCl <10 mL/minute: Reduce continuous infusion dose by 50% to 75% (Bauer 2008). Monitor procainamide/NAPA concentrations closely.
Procainamide: Moderately hemodialyzable (20% to 50%); NAPA: Not dialyzable (0% to 5%): Monitor procainamide/N-acetylprocainamide (NAPA) concentrations; supplementation may be necessary (Aronoff 2007)
Procainamide/NAPA: Not peritoneal dialyzable (0% to 5%) (Aronoff 2007)
Continuous renal replacement therapy (CRRT): In patients with chronic kidney disease receiving CRRT, reduce maintenance dose by 50%. In patients with anuria receiving CRRT, further dosage reduction may be required; use of an initial 1 mg/minute continuous infusion dose has been suggested. Monitor procainamide/NAPA concentrations closely (Mohamed 2013).
Dosing: Hepatic Impairment
Manufacturer’s labeling: Manufacturer recommends reduction in frequency of administration; specific frequency reduction not described; however, close monitoring of procainamide and NAPA concentrations and clinical effectiveness recommended.
Alternate dosing (Bauer, 2008):
Oral [Canadian product]:
Child-Pugh score 8–10: Reduce initial daily dose by 25%. Monitor procainamide/NAPA concentrations closely.
Child-Pugh score >10: Reduce initial daily dose by 50%. Monitor procainamide/NAPA concentrations closely.
Child-Pugh score 8–10: Reduce continuous infusion dose by 25%. Monitor procainamide/NAPA concentrations closely.
Child-Pugh score >10: Reduce continuous infusion dose by 50%. Monitor procainamide/NAPA concentrations closely.
IV: Dilute loading dose to a maximum concentration of 20 mg/mL.
Oral: Do not crush or chew sustained release drug products [Canadian product].
IV: Must dilute prior to IV administration. Dilute loading dose to a maximum concentration of 20 mg/mL; administer loading dose at a maximum rate of 50 mg/minute
Stable in 1/2NS, NS, sterile water for injection; variable stability (consult detailed reference) in D5NS, D5W. Note: 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).
Y-site administration: Incompatible with milrinone.
Store at 20°C to 25°C (68°F to 77°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 to 4 mg/mL, solution is stable at room temperature for 24 hours and for 7 days under refrigeration.
Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification
Amiodarone: May enhance the QTc-prolonging effect of Antiarrhythmic Agents (Class Ia). Amiodarone may increase the serum concentration of Antiarrhythmic Agents (Class Ia). Management: Avoid whenever possible. While considered contraindicated in some places, amiodarone U.S. prescribing information suggests that use could be considered under some circumstances, with careful monitoring. Reduce quinidine or procainamide dose by one third. Avoid combination
Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification
BuPROPion: May increase the serum concentration of OCT2 Substrates. Monitor therapy
Cimetidine: May increase the serum concentration of Procainamide. Management: Consider an alternative H2-receptor antagonist in patients taking procainamide. If combined, monitor for increased therapeutic effects/toxicity of procainamide. Consider therapy modification
Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy
CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification
Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Fingolimod: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia). Avoid combination
Highest Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of other Highest Risk QTc-Prolonging Agents. Avoid combination
Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Indapamide: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Consider therapy modification
Ivabradine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
LamoTRIgine: May increase the serum concentration of Procainamide. Management: Consider monitoring for increased procainamide concentrations and/or systemic effects in patients receiving procainamide with lamotrigine. The lamotrigine Canadian product monograph states that coadministration of these agents is not recommended. Monitor therapy
Lurasidone: May enhance the QTc-prolonging effect of Procainamide. Management: Consider alternatives to procainamide in patients with acute lurasidone overdose. If procainamide treatment cannot be avoided, monitor for excessive QTc interval prolongation. Consider therapy modification
MiFEPRIStone: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Moderate Risk QTc-Prolonging Agents: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
Neuromuscular-Blocking Agents: Procainamide may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy
Propafenone: May enhance the arrhythmogenic effect of Antiarrhythmic Agents (Class Ia). Management: Concurrent use of propafenone with quinidine, amiodarone, or other class IA or class III antiarrhythmics should be avoided. Treatment with such agents should be withheld for at least 5 half-lives prior to initiation of propafenone. Avoid combination
QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying): May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
RaNITIdine: May increase the serum concentration of Procainamide. Ranitidine may also increase the concentration of the active N-acetyl-procainamide (NAPA) metabolite. Monitor therapy
Trimethoprim: May increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Consider therapy modification
Vinflunine: May enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Avoid combination
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.
Cardiovascular: Hypotension (IV up to 5%)
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, cerebellar ataxia, confusion, demyelinating polyradiculoneuropathy, 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, mania, mental depression, myasthenia gravis worsened, myocardial contractility depressed, myocarditis, myopathy, neuromuscular blockade, neutropenia, pancreatitis, pancytopenia, paradoxical increase in ventricular rate in atrial fibrillation/flutter, peripheral/polyneuropathy, pleural effusion, positive Coombs' test, proarrhythmia, pseudo-obstruction, psychosis, pulmonary embolism, QTc-interval prolongation, pruritus, rash, respiratory failure due to myopathy, second-degree heart block, tachycardia, thrombocytopenia, torsade de pointes, transaminases increased, urticaria, vasculitis, ventricular fibrillation, weakness
Concerns related to adverse effects:
• Blood dyscrasias: [US 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: [US 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. Avoid use in patients with QT prolongation (ACLS, 2010).
• 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 or avoid (ACLS, 2010) 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.
• Drugs with QT prolongation potential: Avoid concurrent use with other drugs known to prolong QTc interval.
Dosage form specific issues:
• Sodium metabisulfite: The injectable 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. Note: Canadian injectable product does not contain sodium metabisulfite.
• 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.
• CAST trial: [US 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.
ECG, blood pressure, renal function; with prolonged use monitor CBC with differential, platelet count; procainamide and NAPA blood concentrations in patients with hepatic impairment, renal impairment, or receiving constant infusion >3 mg/minute for longer than 24 hours; ANA titers
Consult individual institutional policies and procedures.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted. Procainamide crosses the placenta (Dumesic 1982; Oudijk 2002); procainamide and its active metabolite (N-acetyl procainamide) can be detected in the cord blood and neonatal serum (Pittard 1983). Intravenous procainamide may be considered for the acute treatment of SVT in pregnant women. Due to adverse events (lupus-like syndrome), long term therapy should be avoided unless other options are not available (Page [ACC/AHA/HRS 2015]).
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience injection site pain or irritation. Have patient report immediately to prescriber signs of infection, bruising, bleeding, signs of liver problems (dark urine, feeling tired, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin or eyes), angina, depression, mood changes, hallucinations, severe nausea, vomiting, joint pain, joint edema, diarrhea, severe dizziness, passing out, tachycardia, bradycardia, arrhythmia, mouth sores, muscle pain, muscle weakness, seizures, or shortness of breath (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.