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.
Dosage guidance:
Dosing: To calculate dose, some experts use actual body weight, and others use ideal body weight (Ref).
Clinical considerations: Not recommended to treat cardiac arrest due to ventricular fibrillation or pulseless ventricular tachycardia due to lack of efficacy and prolonged administration time (Ref).
Atrial fibrillation with preexcitation, hemodynamically stable (off-label use):
Loading dose: IV: Initial: 20 to 50 mg/minute until a maximum of 17 mg/kg is administered, the arrhythmia is controlled, or hypotension occurs (Ref). Some experts do not exceed 15 mg/kg or a maximum dose of 1.5 g (Ref).
Maintenance infusion: Note: Once the arrhythmia terminates, seek an alternative agent for ongoing management; use of procainamide for more than 12 to 24 hours is associated with significant toxicity (eg, torsades de pointes) and requires monitoring by an experienced clinician (eg, QRS interval, QTc interval, procainamide and N-acetyl procainamide serum concentrations) (Ref).
Continuous infusion: IV: 1 to 4 mg/minute (Ref). Some experts use higher infusion rates (eg, up to 6 to 10 mg/minute) (Ref).
Atrioventricular reentrant tachycardia, antidromic or orthodromic, hemodynamically stable (off-label use ):
Note: Procainamide is a preferred agent for acute treatment of antidromic atrioventricular reentrant tachycardia (AVRT). In known orthodromic AVRT, procainamide is an alternative to atrioventricular nodal blocking agents (Ref).
Loading dose: IV: Initial: 20 to 50 mg/minute until a maximum of 17 mg/kg is administered, arrhythmia is controlled, or hypotension occurs (Ref). Some experts do not exceed 15 mg/kg or a maximum dose of 1.5 g (Ref).
Maintenance infusion: Note: Once the arrhythmia terminates, seek an alternative agent for ongoing management; use of procainamide for more than 12 to 24 hours is associated with significant toxicity (eg, torsades de pointes) and requires monitoring by an experienced clinician (eg, QRS interval, QTc interval, procainamide, N-acetyl procainamide serum concentrations) (Ref).
Continuous infusion: IV: 1 to 4 mg/minute (Ref). Some experts use higher infusion rates (up to 6 to 10 mg/minute) (Ref).
Ventricular tachycardia, hemodynamically stable, sustained monomorphic:
Loading dose: IV: Initial: 20 to 50 mg/minute until a maximum of 17 mg/kg is administered, arrhythmia is controlled, or hypotension occurs (Ref). Some experts do not exceed 15 mg/kg or a maximum dose of 1.5 g (Ref).
Maintenance infusion: Note: Once the arrhythmia terminates, seek an alternative agent for ongoing management; use of procainamide for more than 12 to 24 hours is associated with significant toxicity (eg, torsades de pointes) and requires monitoring by an experienced clinician (eg, QRS interval, QTc interval, procainamide, N-acetyl procainamide serum concentrations) (Ref).
Continuous infusion: IV: 1 to 4 mg/minute (Ref). Some experts use up to 6 to 10 mg/minute (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Monitor procainamide and N-acetyl procainamide (NAPA) concentrations.
Altered kidney function:
CrCl >50 mL/minute: No dosage adjustment necessary (Ref).
CrCl 10 to 50 mL/minute: Reduce continuous infusion dose by 25% to 50% (Ref).
CrCl <10 mL/minute: Reduce continuous infusion dose by 50% to 75% (Ref).
Hemodialysis, intermittent (thrice weekly): Procainamide: Moderately hemodialyzable (20% to 50%); NAPA: Not dialyzable (0% to 5%): supplementation may be necessary (Ref).
Peritoneal dialysis: Not significantly dialyzable (procainamide and NAPA) (Ref).
CRRT: Reduce maintenance dose by 50%. In patients with anuria receiving CRRT, further dosage reduction may be required (Ref).
Note: Monitor procainamide and N-acetyl procainamide concentrations.
Child-Pugh score 8 to 10: Reduce continuous infusion dose by 25% (Ref).
Child-Pugh score >10: Reduce continuous infusion dose by 50% (Ref).
Refer to adult dosing. Initiate doses at lower end of dosage range.
(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 (Ref).
Maintenance: Continuous IV infusion: 20 to 80 mcg/kg/minute; maximum daily dose: 2,000 mg/24 hours (Ref).
Oral: 15 to 50 mg/kg/day divided every 3 to 6 hours; maximum daily dose: 4,000 mg/24 hours (Ref).
Resuscitation (Pediatric Advanced Life Support [PALS]):
Supraventricular tachycardia, hemodynamically unstable and shock-refractory (Ref): 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 (Ref): 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 (Ref): 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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
<1%: Hematologic & oncologic: Agranulocytosis, bone marrow depression, hypoplastic anemia, neutropenia, thrombocytopenia
Frequency not defined:
Cardiovascular: Brief ventricular asystole, flushing, ventricular fibrillation
Dermatologic: Maculopapular rash, pruritus
Hypersensitivity: Angioedema
Postmarketing:
Cardiovascular: Bradycardia (Lawson 1977), exacerbation of cardiac arrhythmias, heart block (including first-degree atrioventricular block) (Lawson 1977), hypotension (Lawson 1977), prolonged QT interval on ECG (Foo 2005), pulmonary embolism (Asherson 1989), tachyarrhythmia (Lawson 1977)
Dermatologic: Urticaria (Lawson 1977)
Hematologic & oncologic: Eosinophilia (Lawson 1977), hemolytic anemia, pancytopenia (Shields 1988), positive ANA titer (Asherson 1989)
Hepatic: Granulomatous hepatitis (Rotmensch 1978), hepatic failure, increased serum alkaline phosphatase, increased serum bilirubin, increased serum transaminases, intrahepatic cholestatic jaundice (Chuang 1993)
Nervous system: Asthenia, cerebellar ataxia (Schwartz 1984), depression, dizziness, exacerbation of myasthenia gravis (Drachman 1965), hallucination, mania (Rice 1988), psychosis
Neuromuscular & skeletal: Lupus-like syndrome (Asherson 1989, McDevitt 1967), myopathy (Lewis 1986)
Miscellaneous: Drug fever (Lawson 1977)
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); systemic lupus erythematosus; torsade de pointes.
Canadian labeling: Additional contraindications (not in US labeling): Myasthenia gravis; severe heart failure; kidney failure; shock.
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.
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: Use with caution or avoid in patients with heart failure; may precipitate or exacerbate condition due to negative inotropic actions.
• Kidney impairment: Use with caution in patients with kidney impairment; dosage reduction recommended.
• Myasthenia gravis: Avoid use in myasthenia gravis; may worsen condition.
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 patients with asthma.
Special populations:
• Older adult: Use caution and dose cautiously; renal clearance of procainamide/N-acetyl procainamide declines in patients ≥50 years of age (independent of CrCl 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.
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
Solution (Procainamide HCl Injection)
100 mg/mL (per mL): $10.20 - $72.00
500 mg/mL (per mL): $270.00 - $360.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection, as hydrochloride:
Generic: 100 mg/mL (10 mL)
IV:
Loading dose: Administer at a rate of 20 to 50 mg/minute.
Continuous infusion: Administer at a rate of 1 to 4 mg/minute (Ref).
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 (Ref).
Loading dose:
Neonates: Administer over 60 minutes (Ref).
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 (Ref); Note: Usual adult infusion rate: 20 to 50 mg/minute (Ref).
Divided loading doses (2 to 6 mg/kg/dose up to 100 mg/dose): Administer over ≥5 minutes (Ref).
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, life threatening: Treatment of life-threatening ventricular arrhythmias.
Atrial fibrillation with preexcitation, hemodynamically stable; Atrioventricular reentrant tachycardia, antidromic or orthodromic, hemodynamically stable
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)
Substrate of CYP2D6 (Minor), MATE1/2-K, OCT1, OCT2; Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Ajmaline: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase serum concentration of Ajmaline. Risk X: Avoid
Amiodarone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
Arimoclomol: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Azithromycin (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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
Carbetocin: May increase QTc-prolonging effects of QT-prolonging 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
Ceritinib: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 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 increase QTc-prolonging effects of Citalopram. Risk X: Avoid
Clarithromycin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Clarithromycin. Risk X: Avoid
Clofazimine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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
ClomiPRAMINE: May increase QTc-prolonging effects of QT-prolonging 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
CloZAPine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of Crizotinib. Crizotinib may increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Crizotinib may increase 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
Dabrafenib: May increase QTc-prolonging effects of QT-prolonging 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
Dasatinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Doxepin-Containing Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging 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
Entrectinib: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Erythromycin (Systemic): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Erythromycin (Systemic). Erythromycin (Systemic) may increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Erythromycin (Systemic) may increase 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 increase QTc-prolonging effects 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
Etelcalcetide: May increase QTc-prolonging effects of QT-prolonging 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
Fedratinib: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Fedratinib: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Fexinidazole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Fingolimod: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Flecainide: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
Fluorouracil Products: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Fluorouracil Products. 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 increase QTc-prolonging effects of Flupentixol. Risk X: Avoid
Foslevodopa: May increase serum concentration of MATE1/2-K Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gadobenate Dimeglumine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Gilteritinib: May increase QTc-prolonging effects 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
Givinostat: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Halofantrine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
HydrOXYzine: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk C: Monitor
Iboga: May increase QTc-prolonging effects 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
Imipramine: May increase QTc-prolonging effects of QT-prolonging 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
Inotuzumab Ozogamicin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase adverse/toxic effects of Lacosamide. Specifically the risk for bradycardia, ventricular tachyarrhythmias, or a prolonged PR interval may be increased. Risk C: Monitor
LamoTRIgine: May increase 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
Levofloxacin-Containing Products (Systemic): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Levoketoconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of Levoketoconazole. Risk X: Avoid
Lofexidine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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
Lonafarnib: May increase QTc-prolonging effects of QT-prolonging 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
Meglumine Antimoniate: May increase QTc-prolonging effects of QT-prolonging 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
Methadone: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects of Moxifloxacin (Systemic). Risk X: Avoid
Neuromuscular-Blocking Agents: Procainamide may increase neuromuscular-blocking effects of Neuromuscular-Blocking Agents. Risk C: Monitor
Nilotinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Nilotinib. Risk X: Avoid
OLANZapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
Oxytocin: May increase QTc-prolonging effects of QT-prolonging 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
Pacritinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Pacritinib. 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
PAZOPanib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of PAZOPanib. Risk X: Avoid
Pentamidine (Systemic): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
Piperaquine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Probucol: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Probucol. Risk X: Avoid
Propafenone: May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
Propofol: May increase QTc-prolonging effects of QT-prolonging 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
QT-prolonging Agents (Indeterminate Risk - Avoid): May increase QTc-prolonging effects 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
QT-prolonging Agents (Indeterminate Risk - Caution): May increase QTc-prolonging effects 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
QT-prolonging Class IA Antiarrhythmics (Highest Risk): May increase QTc-prolonging effects of QT-prolonging Class IA Antiarrhythmics (Highest Risk). Risk X: Avoid
QT-prolonging Class III Antiarrhythmics (Highest Risk): QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects of QT-prolonging Class III Antiarrhythmics (Highest Risk). Risk X: Avoid
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging 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
QT-prolonging Kinase Inhibitors (Highest Risk): May increase QTc-prolonging effects 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 increase QTc-prolonging effects 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
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). 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
QUEtiapine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of QUEtiapine. Risk X: Avoid
Quizartinib: May increase QTc-prolonging effects 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
RaNITIdine: May increase serum concentration of Procainamide. Ranitidine may also increase the concentration of the active N-acetyl-procainamide (NAPA) metabolite. Risk C: Monitor
Ribociclib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Ribociclib. Risk X: Avoid
Risdiplam: May increase 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 increase QTc-prolonging effects of RisperiDONE. QT-prolonging Agents (Highest Risk) may increase CNS depressant effects 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 increase QTc-prolonging effects 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
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Highest Risk). Risk X: Avoid
Sparfloxacin: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Sparfloxacin. Risk X: Avoid
SUNItinib: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of SUNItinib. 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
Tafenoquine: May increase 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 serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). 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
Terbutaline: May increase QTc-prolonging effects 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
Thioridazine: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Toremifene: QT-prolonging Agents (Highest Risk) may increase QTc-prolonging effects 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 concentration of Procainamide. Trimethoprim may increase active metabolite exposure 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 increase QTc-prolonging effects 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
Vimseltinib: May increase serum concentration of OCT2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid concomitant use of vimseltinib and OCT2 substrates when possible. If combined, monitor for increased effects and toxicities of the OCT2 substrate and consider dose adjustments. Risk D: Consider Therapy Modification
Voriconazole: QT-prolonging Class IA Antiarrhythmics (Highest Risk) may increase QTc-prolonging effects 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 2016]).
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 (eg, QRS interval and QTc interval), BP, kidney and liver function; with prolonged use monitor CBC with differential and platelet count; procainamide and N-acetyl procainamide blood concentrations, especially in patients with kidney or liver impairment or receiving a continuous infusion for longer than 12 to 24 hours.
Timing of serum samples: Draw 6 to 12 hours after IV infusion has started.
Therapeutic concentrations (approximate): Procainamide: 4 to 10 mcg/mL (SI: 16.9 to 42.3 micromole/L); N-acetyl procainamide 10 to 30 mcg/mL (SI: 36.1 to 108.3 micromole/L); combined: 10 to 30 mcg/mL. Therapeutic index is wide and varies between patients. An effective serum concentration in one patient may cause toxicity in another (Bauer 2008; Boro 2004; Connolly 1982; Giardina 1984).
Toxic concentration: Procainamide: >10 to 12 mcg/mL (SI: >42.3 to 50.8 micromole/L) (occasional toxicity); 12 to 15 mcg/mL (SI: 50.8 to 63.5 micromole/L) (more toxicity); >15 mcg/mL (>63.5 micromole/L) (commonly causes toxicity) (manufacturer’s labeling).
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).
Altered kidney function: Elimination half-life is prolonged.
Older adult: Elimination half-life is prolonged.