The prolonged administration of procainamide often leads to the development of a positive antinuclear antibody (ANA) test, with or without symptoms of a lupus erythematosus-like syndrome. If a positive ANA titer develops, the benefits versus risks of continued procainamide therapy should be assessed.
In the National Heart, Lung and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicenter, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had myocardial infarction more than 6 days but less than 2 years previously, an excessive mortality or nonfatal cardiac arrest rate (7.7%) was seen in patients treated with encainide or flecainide compared with that seen in patients assigned to matched placebo-treated group (3%). The average duration of treatment with encainide or flecainide in this study was 10 months.
The applicability of the CAST results to other populations (eg, those without recent myocardial infarctions) is uncertain. Considering the known proarrhythmic properties of procainamide and the lack of evidence of improved survival for any antiarrhythmic drug in patients without life-threatening arrhythmias, the use of procainamide as well as other antiarrhythmic agents should be reserved for patients with life-threatening ventricular arrhythmias.
Agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia and thrombocytopenia in patients receiving procainamide HCl have been reported at a rate of approximately 0.5%. Most of these patients received procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20 to 25% mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, it is recommended that complete blood counts including white cell, differential and platelet counts be performed at weekly intervals for the first 3 months of therapy, and periodically thereafter. Complete blood counts should be performed promptly if the patient develops any signs of infection (such as fever, chills, sore throat or stomatitis), bruising or bleeding. If any of those hematologic disorders are identified, procainamide therapy should be discontinued. Blood counts usually return to normal within 1 month of discontinuation. Caution should be used in patients with preexisting marrow failure or cytopenia of any type.
Note: Dose must be individualized and titrated to patient response. Use ideal body weight for weight-based doses (Christoff 1983).
Ventricular arrhythmias: Hemodynamically stable, sustained monomorphic ventricular tachycardia (off label): IV:
Loading dose: 10 to 17 mg/kg at a rate of 20 to 50 mg/minute or 100 mg every 5 minutes; administer until arrhythmia is controlled, hypotension occurs, or QRS complex widens by 50% of its original width. Although manufacturer's labeling suggests a maximum total loading dose of 1 g, clinical evidence suggests higher weight based loading doses of up to 17 mg/kg may be needed (ACLS [Neumar 2010]; AHA/ACC/HRS [Al-Khatib 2017]). Note: Not recommended for use in ongoing ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) due to prolonged administration time and lack of efficacy (AHA 2005; AHA/ACC/HRS [Al-Khatib 2017]).
Maintenance infusion: 1 to 4 mg/minute (ACLS [Neumar 2010]; AHA/ACC/HRS [Al-Khatib 2017]). Manufacturer labeling suggests a maintenance infusion of 2 to 6 mg/minute.
Supraventricular arrhythmias:
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 g every 6 hours
Atrial fibrillation (preexcited) (off-label use): IV:
Loading dose: Up to 17 mg/kg at a rate of 20 to 50 mg/minute or 100 mg every 5 minutes; administer until arrhythmia is controlled, hypotension occurs, or QRS complex widens by 50% of its original width. Although manufacturer's labeling suggests a maximum total loading dose of 1 g, clinical evidence suggests higher weight-based loading doses of up to 17 mg/kg may be needed (ACLS [Neumar 2010]).
Maintenance infusion: 1 to 4 mg/minute (ACLS [Neumar 2010]; Hazinski 2015).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Oral [Canadian product]:
Manufacturer’s labeling: Manufacturer recommends increasing dosing interval; specific interval increase not described
Alternate dosing:
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.
IV:
Manufacturer’s labeling: Manufacturer recommends dosage reduction; specific dosage reduction not described; however, close monitoring of procainamide and NAPA concentrations, if facilities are available for measurement, and clinical effectiveness recommended.
Alternate dosing:
CrCl >50 mL/minute: No dosage adjustment necessary (Bauer 2008)
CrCl 10 to 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.
Dialysis:
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).
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.
IV:
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.
(For additional information see "Procainamide: Pediatric drug information")
Note: Cardiology consultation strongly recommended prior to use; use caution when administering procainamide with other drugs that prolong QT interval (eg, amiodarone). Dose must be individualized and titrated based on patient's blood pressure, ECG, and arrhythmia control; monitor serum concentrations (procainamide and N-acetylprocainamide [NAPA]) and QRS complex to avoid toxicity.
Tachyarrhythmia (including junctional ectopic tachycardia [JET], supraventricular tachycardia [SVT], atrial fibrillation, and atrial flutter), treatment: Limited data available:
Infants, Children, and Adolescents:
IV, Intraosseous:
Loading dose: Note: Monitor telemetry and blood pressure closely during administration; if arrhythmia terminates, consider discontinuing loading dose; discontinue or hold loading dose if blood pressure drops below acceptable range:
10 to 15 mg/kg as a single dose infused over 30 to 60 minutes (maximum total loading dose: 500 mg) or the total loading dose may also be divided and given in 2 to 6 mg/kg/dose increments (up to 100 mg/dose) infused over ≥5 minutes and may be repeated every 10 to 30 minutes as needed; maximum adult total loading dose: 1,000 mg; may follow with continuous infusion as clinically appropriate (AAP [Shenoi 2020]; AHA [Marino 2018]; Chang 2010; Gelband 1975; Kliegman 2020; Luedtke 1997; Mandapati 2000; Park 2021; Walsh 1997; manufacturer's labeling).
Maintenance: Continuous IV infusion: 20 to 80 mcg/kg/minute; maximum daily dose: 2,000 mg/24 hours (AAP [Shenoi 2020]; Gelband 1975; Kliegman 2020; Luedtke 1997; Park 2021).
Oral: 15 to 50 mg/kg/day divided every 3 to 6 hours; maximum daily dose: 4,000 mg/24 hours (Kliegman 2020; Park 2021).
Resuscitation (Pediatric Advanced Life Support [PALS]):
Supraventricular tachycardia, hemodynamically unstable and shock-refractory (PALS [Kleinman 2010]): Limited data available:
Infants, Children, and Adolescents: IV, Intraosseous: 15 mg/kg infused over 30 to 60 minutes, rate of infusion depends on urgency of clinical scenario; may give additional doses if clinical endpoint not achieved and no signs of toxicity exist; monitor ECG and blood pressure.
Wide-complex tachycardia of unknown origin (atrial or ventricular), hemodynamically stable (PALS [Kleinman 2010]): Limited data available:
Infants, Children, and Adolescents: IV, Intraosseous: 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.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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; close monitoring of procainamide and N-acetylprocainamide (NAPA) serum concentrations, if facilities are available for measurement, and clinical effectiveness recommended. 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
Dialysis: All patients:
Procainamide: Moderately hemodialyzable (20% to 50%): Monitor procainamide/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
There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested. Use with caution, closely monitor procainamide and NAPA concentrations.
Refer to adult dosing. Initiate doses at lower end of dosage range.
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)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 250 mg, 375 mg [DSC], 500 mg [DSC]
Solution, Injection, as hydrochloride:
Generic: 100 mg/mL (10 mL)
Tablet Extended Release, Oral:
Procan SR: 250 mg
Oral: Canadian product: Do not crush or chew sustained-release drug products.
Bariatric surgery: Tablet, sustained release: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR capsule, tablet, and injectable formulations are available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery; however, the selection of IR capsules, tablets, or IM/IV formulations should be strongly considered for procainamide after bariatric surgery.
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
Parenteral: IV: Note: Infusion rate should be decreased if QT interval becomes prolonged or patient develops heart block; discontinue the infusion if patient develops hypotension or QRS interval widens to >50% of baseline; severe hypotension can occur with rapid IV administration (PALS [Kleinman 2010]).
Loading dose:
Neonates: Administer over 60 minutes (Moffett 2006).
Infants, Children, and Adolescents: Note: Close monitoring is recommended to assess clinical response and adverse drug reactions; rate of administration varies depending on type of dosing; use precaution:
Single loading dose (10 to 15 mg/kg up to 500 mg): Administer total dose over 30 to 60 minutes (AAP [Shenoi 2020]; AHA [Marino 2018]; PALS [Kleinman 2010]; Note: Usual adult infusion rate: 20 to 50 mg/minute (AAP [Hegenbarth 2008]; PALS [Kleinman 2010]; manufacturer's labeling).
Divided loading doses (2 to 6 mg/kg/dose up to 100 mg/dose): Administer over ≥5 minutes (Gelband 1975; Park 2021).
Continuous IV infusion: Administer via an infusion pump.
IV infusion: 1000 mg in 500 mL (concentration: 2 mg/mL), 1000 mg in 250 mL (concentration: 4 mg/mL), or 2000 mg in 250 mL (concentration: 8 mg/mL) of D5W or NS
Ventricular arrhythmias: Intravenous: Treatment of life-threatening ventricular arrhythmias
Supraventricular 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.
Atrial fibrillation (preexcited); Junctional tachycardia; Stable monomorphic ventricular tachycardia
Procanbid may be confused with probenecid, Procan SR
Pronestyl may be confused with Ponstel
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)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Hematologic & oncologic: Positive ANA titer (≤50%)
Neuromuscular & skeletal: Lupus-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, skin rash)
1% to 10%:
Cardiovascular: Hypotension (intravenous: ≤5%)
Dermatologic: Skin rash
Gastrointestinal: Diarrhea (oral: 3% to 4%), dysgeusia (oral: 3% to 4%), nausea (oral: 3% to 4%), vomiting (oral: 3% to 4%)
<1%, postmarketing, and/or case reports: Agranulocytosis, angioedema, anorexia, aplastic anemia, arthralgia, asystole, bone marrow depression, cerebellar ataxia, confusion, demyelinating disease (demyelinating polyradiculoneuropathy), depression, depression of myocardial contractility, disorientation, dizziness, drug fever, exacerbation of cardiac arrhythmia, exacerbation of myasthenia gravis, fever, first degree atrioventricular block, flushing, gastrointestinal pseudo-obstruction, granulomatous hepatitis, hallucination, hemolytic anemia, hepatic failure, hyperbilirubinemia, hypoplastic anemia, increased serum alkaline phosphatase, increased serum transaminases, intrahepatic cholestasis, leukopenia, maculopapular rash, mania, myocarditis, myopathy, neuromuscular blockade, neutropenia, pancreatitis, pancytopenia, peripheral neuropathy, pleural effusion, polyneuropathy, positive direct Coombs test, prolonged QT interval on ECG, psychosis, pruritus, pulmonary embolism, second degree atrioventricular block, tachycardia, thrombocytopenia, torsades de pointes, urticaria, vasculitis, ventricular fibrillation, ventricular tachycardia (paradoxical; in atrial fibrillation/flutter), weakness
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
Canadian labeling: Additional contraindications (not in US labeling):Myasthenia gravis; severe heart failure (IV); renal failure (IV); shock (IV)
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).
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 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.
Dosage form specific issues:
• Sodium metabisulfite: The injectable product may contain sodium metabisulfite which can 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: [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.
Substrate of CYP2D6 (minor), OCT2; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Ajmaline: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase the serum concentration of Ajmaline. Risk X: Avoid combination
Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Amiodarone. Management: Consider alternatives to this drug combination. If combined, consider dose reductions of the class IA antiarrhythmic (30% to 50%) and monitor for QTc interval prolongation and ventricular arrhythmias. Risk D: Consider therapy modification
Amisulpride (Oral): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Amisulpride (Oral). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even greater risk. Risk D: Consider therapy modification
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ceritinib: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ceritinib. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Chloroquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
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. Risk D: Consider therapy modification
Citalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Citalopram. Risk X: Avoid combination
Clarithromycin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clarithromycin. Risk X: Avoid combination
Clofazimine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
CloZAPine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of CloZAPine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Crizotinib: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Crizotinib. Crizotinib may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Dasatinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Domperidone: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Droperidol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Entrectinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Erdafitinib: May increase the serum concentration of OCT2 Substrates. Risk C: Monitor therapy
Erythromycin (Systemic): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Erythromycin (Systemic). Erythromycin (Systemic) may enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Erythromycin (Systemic) may increase the serum concentration of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Escitalopram: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Escitalopram. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Fexinidazole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Risk X: Avoid combination
Fingolimod: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
Flecainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flecainide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Fluconazole: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Flupentixol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Flupentixol. Risk X: Avoid combination
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Gemifloxacin: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
Gilteritinib: May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. If use is necessary, monitor for QTc interval prolongation and arrhythmias. Risk D: Consider therapy modification
Halofantrine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Halofantrine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Haloperidol: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Inotuzumab Ozogamicin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Lacosamide: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the adverse/toxic effect of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor therapy
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. Risk C: Monitor therapy
Levofloxacin-Containing Products (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
Levoketoconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Lofexidine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Lofexidine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Midostaurin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Midostaurin. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Moxifloxacin (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Moxifloxacin (Systemic). Risk X: Avoid combination
Neuromuscular-Blocking Agents: Procainamide may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy
Nilotinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Nilotinib. Risk X: Avoid combination
OLANZapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Ondansetron: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Osimertinib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Osimertinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pilsicainide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pilsicainide. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Pimozide: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Pimozide. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk X: Avoid combination
Piperaquine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Probucol: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Probucol. Risk X: Avoid combination
Propafenone: May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
QT-prolonging Agents (Indeterminate Risk - Avoid): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Agents (Indeterminate Risk - Caution): May enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May enhance the QTc-prolonging effect of other QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid combination
QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid combination
QT-prolonging Kinase Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Miscellaneous Agents (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Highest Risk). Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QUEtiapine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination
RaNITIdine (Withdrawn from US Market): 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
Ribociclib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Ribociclib. Risk X: Avoid combination
Risdiplam: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of risdiplam with MATE substrates if possible. If the combination cannot be avoided, monitor closely for adverse effects. Consider a reduced dose of the MATE substrate according to that substrate's labeling if appropriate. Risk D: Consider therapy modification
RisperiDONE: QT-prolonging Agents (Highest Risk) may enhance the CNS depressant effect of RisperiDONE. QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Saquinavir: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Saquinavir. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Sodium Stibogluconate: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sodium Stibogluconate. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Sparfloxacin: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Sparfloxacin. Risk X: Avoid combination
Tafenoquine: May increase the serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Management: Avoid use of MATE substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the MATE substrate and consider a reduced dose of the MATE substrate according to that substrate's labeling. Risk D: Consider therapy modification
Tafenoquine: May increase the serum concentration of OCT2 Substrates. Management: Avoid use of OCT2 substrates with tafenoquine, and if the combination cannot be avoided, monitor closely for evidence of toxicity of the OCT2 substrate and consider a reduced dose of the OCT2 substrate according to that substrate's labeling. Risk D: Consider therapy modification
Thioridazine: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Thioridazine. Risk X: Avoid combination
Toremifene: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Toremifene. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Trimethoprim: May increase serum concentrations of the active metabolite(s) of Procainamide. Trimethoprim may increase the serum concentration of Procainamide. Management: Consider alternatives to trimethoprim-containing regimens to avoid this interaction. If coadministered, monitor for increased procainamide adverse effects (increased QTc) if trimethoprim is initiated/dose increased. Risk D: Consider therapy modification
Vemurafenib: QT-prolonging Agents (Highest Risk) may enhance the QTc-prolonging effect of Vemurafenib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
Voriconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may enhance the QTc-prolonging effect of Voriconazole. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
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]).
Procainamide and its metabolite are present in breast milk and concentrations may be higher than in the maternal serum. In a case report, procainamide was used throughout pregnancy with a dose of 2 g/day prior to delivery. After birth (39 weeks' gestation), milk and maternal serum concentrations were obtained over 15 hours of a dosing interval. Mean maternal serum concentrations were procainamide 1.1 mcg/mL and N-acetyl procainamide 1.6 mcg/mL. Mean milk concentrations were procainamide 5.4 mcg/mL and N-acetyl procainamide 3.5 mcg/mL (Pittard 1983). According to the manufacturer, the decision to continue or discontinue breastfeeding during therapy should take into account the risk of exposure to the infant and the benefits of treatment to the mother.
ECG (with attention to the QRS duration and QT interval), 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 with chronic oral use
Consult individual institutional policies and procedures.
Timing of serum samples: Draw 6 to 12 hours after IV infusion has started; half-life is 2.5 to 5 hours
Therapeutic concentrations: Procainamide: 4 to 10 mcg/mL; NAPA 15 to 25 mcg/mL; Combined: 10 to 30 mcg/mL
Toxic concentration: Procainamide: >10 to 12 mcg/mL
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: IM 10 to 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 to 4.7 hours; Anephric: 11 hours
NAPA (dependent upon renal function): Children: 6 hours; Adults: 6 to 8 hours; Anephric: 42 hours
Time to peak, serum: IM: 15 to 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).
Renal function impairment: Elimination half-life is prolonged.
Geriatric: Elimination half-life is prolonged.
Solution (Procainamide HCl Injection)
100 mg/mL (per mL): $10.20 - $36.00
500 mg/mL (per mL): $43.66 - $180.00
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