Procainamide (Procanbid) - Uses, Dose, MOA, Brands, Side effects

The anti-arrhythmic medication procainamide (Procanbid, Pronestyl) belongs to class 1a.

It prevents the sodium channels from opening after repolarization and stops their function.

It treats ventricular and supraventricular cardiac arrhythmias and lowers membrane excitability.

Procainamide labeled Uses:

  • Ventricular arrhythmias:

    • Treatment is available for life-threatening ventricular arrhythmias. 

  • Supraventricular arrhythmias:
    • SVT treatment..

Note:  Use only in situations where the first line of treatment is ineffective or impractical for the treatment of atrial fibrillation

It is utilised when reflex stimulation or other treatments are ineffective: paroxysmal atrial tachycardia

  • Procainamide Off-Label Uses:

    • Atrial fibrillation (pre excited);

    • Junctional tachycardia;

    • Stable monomorphic ventricular tachycardia

 

Procainamide dose in Adults:

Note: Must tailor and adjust dosage based on patient response. For weight-based dosing, the ideal body weight should be applied.

 

Procainamide dose in Ventricular arrhythmias: 

  • IV treatment for sustained monomorphic ventricular tachycardia with hemodynamic stability (off label): 

    • The patient should receive the loading dose of 10 to 17 mg/kg at a rate of 20 to 50 mg/minute, or 100 mg every 5 minutes until the arrhythmia is stabilized, the patient becomes hypotensive, or the QRS complex widens by half of its initial width. 

    • Clinical evidence indicates that greater weight-based loading doses of up to 17 mg/kg may be required, despite the manufacturer's labeling suggesting a maximum total loading dose of 1 g. 

Note: Due to the prolonged administration duration and lack of effectiveness, do not use in persistent ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT). 

Infusion rate for maintenance: 1 to 4 mg/min. The maintenance infusion dose, as stated on the manufacturer's label, ranges from 2 to 6 mg/minute

Procainamide dose in Supraventricular arrhythmias:

Oral [Canadian product]: Sustained release formulation (Procan SR):

  • Maintenance: 50 mg/kg/day given in divided doses every 6 hours.
  • Suggested Procan SR maintenance dose:
  • <55 kg: 500 mg every 6 hours apart
  • 55 to 91 kg: 750 mg every 6 hours apart
  • >91 kg: 1 g every 6 hours apart

Procainamide dose in Atrial fibrillation (pre-excited) (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; should be administered until arrhythmia is controlled, the patient becomes hypotensive, or QRS complex widening occurs by 50% of its original width.
  • Although the manufacturer's labeling has suggested a maximum total loading dose of 1 g, clinical evidence has suggested higher weight-based loading doses of up to 17 mg/kg may be needed.
  • Maintenance infusion: 1 to 4 mg/minute.

Dosage adjustment for concomitant therapy:

  • Significant medication interactions need for either dose/frequency modification or avoidance. 

Procainamide dose in Children:

Note: It is highly advised to visit a cardiologist before use; care should be used when combining procainamide with medications that extend the QT interval (eg, amiodarone).

To prevent toxicity, it is necessary to customise and titrate the dose based on the patient's blood pressure, ECG, and arrhythmia control; procainamide and N-acetyl procainamide [NAPA] serum concentrations should be monitored.

Treatment of tachyarrhythmias, such as junctional ectopic tachycardia (JET), supraventricular tachycardia (SVT), atrial fibrillation, and atrial flutter, using procainamide dosage

  • IV, Intraosseous:
    • Loading dose: 
    • Note: Telemetry and blood pressure should be constantly watched throughout administration; if an arrhythmia terminates, stopping the loading dose should be considered, and if substantial hypotension develops, stopping or holding the loading dose should be considered
    • 10 to 15 mg/kg in a stat dose infused over 30 to 60 minutes (maximum total loading dose: 500 mg) or may also divide total loading and administer in 2 to 6 mg/kg/dose increments (up to 100 mg/dose) infused over ≥5 minutes and may repeat every 10 to 30 minutes as per need;
    • The maximum adult total loading dose is 1,000 mg, which may be followed by continuous infusion as clinically indicated. 
    Maintenance:

    • Continuous IV infusion rates range from 20 to 80 mcg/kg/minute, with a daily dosage cap of 2,000 mg.

    Oral:

    • The highest daily dose is 4,000 mg per day, which is divided into doses of 15 to 50 mg/kg per 24 hours every 3 to 6 hours.

During resuscitation [Pediatric Advanced Life Support (PALS)], procainamide dosage:

  • Hemodynamic instability, supraventricular tachycardia, and shock resistance 

    • The pace of the 15 mg/kg intraosseous infusion is determined by the urgency of the clinical scenario; additional doses may be given if the clinical endpoint is not met and no indicators of toxicity are present; blood pressure and the ECG should be monitored. 

  • Hemodynamically stable wide-complex tachycardia of unclear origin (atrial or ventricular): 

    • Infusion should be stopped if blood pressure declines or the QRS complex widens by more than 50% of baseline. IV, Intraosseous: 15 mg/kg infusion given over 30 to 60 minutes.

Procainamide Dosage adjustment for concomitant therapy:

  • There are important pharmacological interactions that may call for a change in dosage or frequency or even avoidance.
  • For more details, consult the database of medication interactions.

Pregnancy Risk Factor: C

  • The placenta is crossed by procainamide.
  • Procainamide can be found in newborn serum and cord blood.
  • Acute SVT in pregnant women may be treated with IV procainamide.
  • Avoid long-term therapy if other options aren't accessible because it can result in unfavorable consequences like lupus-like syndrome.

Use during breastfeeding:

Procainamide and its metabolite may be present in breast milk at levels higher than those found in maternal serum.

Breastfeeding should be taken into account while receiving treatment, claims the company.

Both the benefits to the mother and the risks to the child should be considered while making this choice.


Procainamide Dose in Kidney disease:

Adults with renal problems should take procainamide at the following dose

  • Oral [Canadian product]:
    • The following is the manufacturer's labelling: The company advises extending the dosage interval. 
  • Alternate dosing:
    • CrCl >50 mL/minute: No dosage modification is required 
    • CrCl 10 to 50 mL/minute: The initial daily dose ought to be decreased by 25% to 50%. 
    • CrCl <10 mL/minute: The first daily dose should be decreased by 50% to 75% while procainamide/NAPA concentrations are closely watched. 
  • IV:
    • Manufacturer’s labeling:
      • The manufacturer advises dosage reduction, but no information about a particular dosage decrease has been provided. Procainamide and NAPA concentrations should be regularly monitored. 
  • Alternate dosing:
    • CrCl >50 mL/minute: No dosage modification is required 
    • CrCl 10 to 50 mL/minute: The dose of the continuous infusion should be reduced by 25% to 50%.
    • CrCl <10 mL/minute: Procainamide/NAPA concentrations should be closely watched while the dose of the continuous infusion should be reduced by 50% to 75%.

Dialysis:

  • Procainamide: It has a modest hemodialyzability range (20–50%);
  • NAPA: Not dialyzable (0 to 5 percent): Procainamide/N-acetyl procainamide (NAPA) concentrations should be checked; supplementation may be necessary.
  • Procainamide/NAPA: Not dialyzable in the peritoneum (0 percent to 5 percent )
  • Renal replacement therapy that is ongoing (CRRT):
    • The maintenance dose should be reduced by 50% in CRRT patients with chronic renal disease. In patients with anuria receiving CRRT, further lowering might be necessary; it has been recommended to start with a dose of 1 mg/minute for continuous infusion. Concentrations of procainamide and NAPA need to be carefully watched.

Children with Kidney Disease and Procainamide Dose:

  • Children, infants, and adolescents:
    • The manufacturer's labelling makes no precise recommendations; therefore, the dose must be tailored to the patient's reaction and increased or decreased as needed. Procainamide and N-acetyl procainamide (NAPA) serum concentrations should also be continuously monitored. 

Recommendations for renally adjusted doses are based on a loading dosage of 15 mg/kg total. 

  • GFR less than 10 mL/min/1.73 m2: 
  • Dosage of loading dosage reduction to 12 mg/kg 
  • Sustaining infusion: Start at the lower end of the 20 to 80 mcg/kg/minute continuous infusion range.

Dialysis: All patients:

  • Procainamide has a moderate hemodialyzability range of 20% to 50%. Monitoring procainamide/NAPA levels is important; supplementation may be necessary.
  • Not dialyzable (NAPA) (0 percent to 5 percent )
  • Procainamide/NAPA: Not dialyzable in the peritoneum (0 percent to 5 percent )
  • Procainamide/NAPA: During continuous arteriovenous or venovenous hemofiltration, blood level should be substituted for procainamide.

Procainamide Dose in Liver disease:

Dose in Adults with Liver disease:

  • Manufacturer’s labeling:
    • Reduced dosing frequency has been advised by the manufacturer, and clinical efficacy and procainamide and NAPA concentrations should be continuously monitored.
  • Alternate dosing:
    • Oral [Canadian product]:
    • Child-Pugh score 8-10: Procainamide/NAPA concentrations should be closely watched while the first daily dose should be decreased by 25%. 
    • Child-Pugh score >10: Procainamide/NAPA concentrations should be closely watched, and the first daily dose should be cut in half. 
  • IV:
    • Child-Pugh score 8-10: Procainamide/NAPA concentrations should be closely watched while the first daily dose should be decreased by 25%. 
    • Child-Pugh score >10: Procainamide/NAPA concentrations should be closely watched, and the first daily dose should be cut in half.

Dose in children with liver disease:

  • Although there are no recommendations specifically for children, adjusting the dose is advised based on knowledge gained from treating adult patients.
  • Use with caution and keep a close eye on the concentrations of procainamide and NAPA.

Common Side effects of Procainamide:

Hematologic & oncologic:

Positive ANA titer

Neuromuscular & skeletal:

Lupus-like syndrome (increased incidence with long-term therapy or slow acetylators; the syndrome may include features of SLE such as abdominal pain, arthralgia, arthritis, chills, fever, hepatomegaly, myalgia, pericarditis, pleural effusion, pulmonary infiltrates, and skin rash)

Less common Side effects of Procainamide:

Cardiovascular:

  • Hypotension

Dermatologic:

  • Skin rash

Gastrointestinal:

  • Diarrhea
  • dysgeusia
  • nausea
  • vomiting

Rare Side effects of Procainamide:

Blood-related:

 

  • Agranulocytosis,
  • pancytopenia,
  • aplastic anemia,
  • bone marrow suppression,
  • hemolytic anemia,
  • leukopenia,
  • neutropenia,
  • thrombocytopenia
  • positive direct Coombs test

Heart-related:

 

  • asystole,
  • reduced myocardial contractility,
  • a worsening of the heart rhythm,
  • atrioventricular block in the first degree,
  • second-degree atrioventricular block,
  • myocarditis,
  • prolonged QT interval on ECG,
  • tachycardia,
  • torsades de pointes,
  • ventricular fibrillation,
  • paradoxical ventricular tachycardia

 

Brain-related:

  • cerebellar ataxia,
  • confusion,
  • hallucination,
  • demyelinating polyradiculoneuropathy,
  • exacerbation of myasthenia gravis,
  • myopathy,
  • neuromuscular blockade,
  • peripheral neuropathy,
  • weakness

 

Psychiatric:

  • depression,
  • disorientation,
  • dizziness,
  • mania,
  • psychosis

 

Vascular:

  • drug fever,
  • flushing,
  • vasculitis,
  • arthralgia,
  • angioedema

 

GI-related:

  • gastrointestinal pseudo-obstruction,
  • granulomatous hepatitis,
  • hepatic failure,
  • hyperbilirubinemia,
  • increased serum alkaline phosphatase,
  • increased serum transaminases,
  • intrahepatic cholestasis,
  • pancreatitis

 

Skin-related:

  • maculopapular rash,
  • pruritus,
  • Urticaria
  •  

Lung-related:

  • pleural effusion,
  • pulmonary embolism

Procainamide contraindications:

  • Hypersensitivity to any ingredient in the formulation, including procainamide, procaine, or other ester-type local anaesthetics 
  • Full-blown heart block 
  • AV block in the second degree or different hemiblocks (without an artificial pacemaker functional)
  • SLE
  • Torsade de Pointes

Canadian labeling. Additional contraindications (not in US labels)

  • Myasthenia gravis
  • Severe heart failure (IV)
  • IV. Renal Failure
  • Shock (IV).

Warnings and precautions

  • Blood dyscrasias:[US Boxed Warning]

    • It can cause fatal blood disorders (eg, Agranulocytosis) if given in therapeutic doses.
    • Monitor weekly for the first three months and then every other week thereafter. Stop taking the medication if you develop blood dyscrasias.

  • Conduction disturbances:

    • If a first-degree blockage of the heart occurs, the dose should be decreased.

  • Drug-induced lupus, erythematosus-like condition:[US Boxed Warning]

    • Long-term administration may lead to a positive antinuclear antibody test (ANA) in 50% of patients. This could cause a drug-induced, lupus-like syndrome in 20% to 30% of patients.
    • You can choose to discontinue the agent or find another one.

  • Proarrhythmic effects

    • Pay attention to proarrhythmic symptoms; adjust the dose as necessary to prevent QTc prolongation. Do not use it in patients suffering from QT prolongation.

Concerns about diseases:

  • Flutter and atrial fibrillation:

    • Patients with atrial fibrillation and flutter may have a higher ventricular response rate. Before initiating, it is important to control AV conduction.

  • Electrolyte imbalance:

    • It is important to correct electrolyte disturbances (hypokalemia and hypomagnesemia).

  • Heart failure (HF):

    • Patients with HF should be cautious about using it. It has a negative inotropic impact and can cause or exacerbate the condition.

  • Myasthenia gravis:

    • Avoid use.

  • Renal impairment

    • You may need to be cautious.

Special populations

  • For the elderly:

    • Be careful
    • Patients >=50 years old experience a decline in renal clearance of procainamide/NAPA, independent of any reductions in creatinine clearance or concomitant renal impairment.

Additional warnings and precautions

  • CAST trial: [US Boxed Warning]

    • Cardiac Arrhythmia Suppression Trial (CAST) did not benefit patients with a myocardial injury who had asymptomatic, non-life-threatening ventricular arrhythmias. They may have been affected by attempts to suppress the arrhythmia using flecainide or an encainide.
    • The active treatment group had a 7.7% higher mortality rate or nonfatal cardiac arrest rate than the placebo group (3%).
    • It is not known if the CAST results can be applied to other populations. Patients with serious ventricular arrhythmias should be allowed to use reserve procainamide.

Procainamide: Drug Interaction

Risk Factor C (Monitor therapy)

CloBAZam

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

Cobicistat

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

CYP2D6 Inhibitors (Moderate)

CYP2D6 substrate metabolism may be decreased (High risk with Inhibitors). 

Darunavir

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

Erdafitinib

OCT2 Substrates' serum concentration can rise. 

Imatinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

Lacosamide

QT-prolonging Class IA Antiarrhythmics (Highest Risk) may exacerbate Lacosamide's negative/toxic effects. Particularly, there may be an increased risk for bradycardia, ventricular tachyarrhythmias, or a longer PR interval. 

LamoTRIgine

May raise procainamide levels in the serum. When administering procainamide along with lamotrigine to patients, management may involve monitoring for elevated procainamide concentrations and/or systemic effects. The coadministration of these medications is not advised, according to the lamotrigine Canadian pharmaceutical monograph. 

Lumefantrine

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

Neuromuscular-Blocking Agents

Neuromuscular-Blocking Agents' ability to block neuromuscular activity may be strengthened by procainamide. 

Panobinostat

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). 

Peginterferon Alfa-2b

May lower the serum level of CYP2D6 substrates (High risk with Inhibitors). The concentration of CYP2D6 Substrates in the serum may rise when using Peginterferon Alfa-2b (High risk with Inhibitors). 

Perhexiline

The serum levels of perhexiline may increase when exposed to CYP2D6 Substrates (High Risk with Inhibitors). The serum concentration of CYP2D6 Substrates may rise in response to perhexiline (High risk with Inhibitors).

QT-prolonging Agents (Indeterminate Risk - Avoid)

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

QT-prolonging Agents (Indeterminate Risk - Caution)

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). When using these medications together, watch out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

RaNITIdine

  

May raise procainamide levels in the serum. The active N-acetyl-procainamide (NAPA) metabolite's concentration may also rise in response to ranitidine.

Risk Factor D (Consider therapy modification)

Abiraterone Acetate

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). Management: Whenever feasible, avoid using abiraterone at the same time as CYP2D6 substrates with a limited therapeutic index. When concurrent usage cannot be avoided, patients should be closely watched for toxicity symptoms and signs.

Amiodarone

The QTcprolonging effect of amiodarone may be enhanced by QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Amisulpride

Amisulpride's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Asunaprevir

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors).

Azithromycin (Systemic)

The QTc-prolonging effect of azithromycin may be enhanced by QT-prolonging agents (Highest Risk) (Systemic). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Ceritinib

The QTcprolonging action of ceritinib may be enhanced by QT-prolonging Class IA Antiarrhythmics (Highest Risk). Ceritinib may increase the effect of Class IA antiarrhythmics that prolong QTc (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Chloroquine

Chloroquine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Cimetidine

May raise procainamide levels in the serum. When treating patients who are on procainamide, take into account a different H2-receptor antagonist. If coupled, keep an eye out for procainamide's increased therapeutic effects or toxicity.

Clofazimine

The QTc-prolonging action of clofazimine may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

CloZAPine

The QTc-prolonging action of CloZAPine may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Crizotinib

The QTcprolonging action of crizotinib may be enhanced by QT-prolonging Class IA antiarrhythmics (Highest Risk). Crizotinib may increase the effect of Class IA antiarrhythmics that prolong QTc (Highest Risk). Crizotinib may raise the serum levels of Class IA antiarrhythmics that prolong QT (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

CYP2D6 Inhibitors (Strong)

CYP2D6 substrate metabolism may be decreased (High risk with Inhibitors).

Dacomitinib

May elevate CYP2D6 Substrates' serum concentration (High risk with Inhibitors). Management: Steer clear of using dacomitinib at the same time as CYP2D6 subtrates with a limited therapeutic index.

Dasatinib

Dasatinib's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Doxepin-Containing Products

The QTcprolonging action of products containing doxepin may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Droperidol

Droperidol's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. 

Encorafenib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Erythromycin (Systemic)

Erythromycin's ability to prolong QT intervals may be enhanced by QT-prolonging Class IA antiarrhythmics (Highest Risk) (Systemic). Erythromycin (Systemic) may increase the effect of Class IA antiarrhythmics that prolong QT by increasing QTc (Highest Risk). The serum concentration of QT-prolonging Class IA Antiarrhythmics may be increased by systemic erythromycin (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Escitalopram

Escitalopram's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Flecainide

Flecainide's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. 

Fluconazole

Could intensify the QT-prolonging effects of class Ia antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Gadobenate Dimeglumine

Gadobenate Dimeglumine's ability to prolong QT intervals may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Gilteritinib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). Management: Take into account alternatives to this fusion. If use is required, keep an eye out for arrhythmias and a prolonged QTc interval.

Halofantrine

The QTc-prolonging action of halofantrine may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Haloperidol

The QTcprolonging action of haloperidol may be enhanced by QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Inotuzumab Ozogamicin

Inotuzumab ozogamicin may have a greater QTc-prolonging impact when used with QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Lofexidine

The QTc-prolonging action of lofexidine may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Lurasidone

May increase Procainamide's ability to prolong QTc. In patients with acute lurasidone overdose, consider procainamide's alternatives. When procainamide medication is unavoidable, keep an eye out for excessive QTc interval lengthening. 

Methadone

The QTcprolonging action of methadone may be strengthened by QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Midostaurin

The QTc-prolonging effect of midostaurin may be strengthened by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

OLANZapine

  

OLANZapine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Ondansetron

The QTcprolonging impact of ondansetron may be enhanced by QT-prolonging Class IA antiarrhythmics (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Osimertinib

 Osimertinib's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations.

Pentamidine (Systemic)

 Pentamidine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk) (Systemic). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Pilsicainide

 Pilsicainide's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Propafenone

Could intensify the QT-prolonging effects of class Ia antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

QT-prolonging Kinase Inhibitors (Highest Risk)

Could intensify the QTc-prolonging effects of class Ia antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Miscellaneous Agents that prolong- QT (Highest Risk)

The QTc-prolonging impact of QT-prolonging Miscellaneous Agents may be enhanced by QT-prolonging Class IA Antiarrhythmics (Highest Risk) (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

RisperiDONE

The CNS depressive action of RisperiDONE may be enhanced by QT-prolonging Agents (Highest Risk). The QTc-prolonging action of RisperiDONE may be strengthened by QT-prolonging Agents (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Saquinavir

The QTcprolonging action of saquinavir may be enhanced by QT-prolonging Class IA antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Sodium Stibogluconate

The QTc-prolonging effect of sodium stibogluconate may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors.

Tafenoquine

MATE1 Substrates' serum concentration might rise. Management: If using MATE substrates with tafenoquine cannot be avoided, check carefully for signs of toxicity and take into account using a lower dose of the MATE substrate in accordance with the labelling of that substrate.

Tafenoquine

OCT2 Substrates' serum concentration can rise. Management: If using OCT2 substrates with tafenoquine cannot be avoided, watch closely for any signs of toxicity and take into account using a lower dose of the OCT2 substrate in accordance with the labelling of that substrate.

Trimethoprim

May raise the active metabolite(s) of procainamide's serum level. Procainamide levels in the serum may rise when taking trimethoprim.

Vemurafenib

Vemurafenib's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. 

Voriconazole

The QTcprolonging action of voriconazole may be enhanced by QT-prolonging Class IA Antiarrhythmics (Highest Risk). Management: Take into account different pharmacological combinations. If combined, keep an eye out for cardiac arrhythmias and a prolonged QTc interval. Patients may be considerably more at risk for QTc prolongation if they have additional risk factors. 

Risk Factor X (Avoid combination)

Ajmaline

Could intensify the QT-prolonging effects of class Ia antiarrhythmics (Highest Risk). The serum levels of ajmaline may rise after taking Class IA Antiarrhythmics (Highest Risk). 

Citalopram

 Citalopram's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk).

Clarithromycin

  

Clarithromycin's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). 

Domperidone

The QTc-prolonging action of Domperidone may be strengthened by QT-prolonging Agents (Highest Risk). 

Entrectinib

Could make QT-prolonging agents' effect on QTc longer (Highest Risk). 

Fingolimod

Could intensify the QT-prolonging effects of class Ia antiarrhythmics (Highest Risk). 

Flupentixol

Flupentixol's ability to prolong QTc may be enhanced by QT-prolonging Agents (Highest Risk). 

Gemifloxacin

Could intensify the QT-prolonging effects of class Ia antiarrhythmics (Highest Risk). 
Products containing levofloxacin (Systemic)

Could intensify the QTc-prolonging effects of class Ia antiarrhythmics (Highest Risk).

Moxifloxacin (Systemic)

Moxifloxacin's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk) (Systemic). 

Nilotinib

The QTc-prolonging action of nilotinib may be strengthened by QT-prolonging agents (Highest Risk). 

Pimozide

The QTc-prolonging action of pimozide may be strengthened by QT-prolonging agents (Highest Risk). Management: Take into account alternatives to this fusion. These toxicities are probably more likely to occur in patients who have additional risk factors, such as advanced age, female sex, bradycardia, hypokalemia, hypomagnesemia, cardiac disease, and higher drug concentrations. 

Piperaquine

The QTc-prolonging action of piperaquine may be enhanced by QT-prolonging Agents (Highest Risk). 

Probucol

Probucol's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk).

QT-prolonging Class IA Antiarrhythmics (Highest Risk

Possibly intensifies the QTc-prolonging effects of other QT-prolonging Class IA antiarrhythmics (Highest Risk). Ajmaline is an exception.

QT-prolonging Class III Antiarrhythmics (Highest Risk)

QT-prolonging Class III Antiarrhythmics may have a greater QTc-prolonging effect when used with QT-prolonging Class IA Antiarrhythmics (Highest Risk) (Highest Risk). 

QUEtiapine

QUEtiapine's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk). 

Ribociclib

Ribociclib's QTc-prolonging effect could be strengthened by QT-prolonging Agents (Highest Risk).

Sparfloxacin

Sparfloxacin's ability to prolong QTc may be enhanced by QT-prolonging agents (Highest Risk).

Thioridazine

The QTc-prolonging action of thioridazine may be strengthened by QT-prolonging Agents (Highest Risk).

 

Monitoring parameters:

  • ECG (with attention to the QRS duration and QT interval)
  • BP
  • RFTs
  • CBC with differential, platelet count when used for long-term
  • Procainamide and NAPA blood concentrations in patients with liver impairment, kidney impairment, or receiving constant infusion >3 mg/minute for longer than 1 day
  • ANA titers with chronic oral use

Consult individual institutional policies and procedures.

Reference Range

Timing of serum samples: Samples should be drawn 6 to 12 hours after the start of IV infusion; the 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.

 

How to administer Procainamide?

Oral:

  • The sustained-release drug products should not be crushed or chewed
  • When treating patients who have undergone bariatric surgery, it is best to use the immediate-release capsule, tablet, and injection. Change in formulation or administration is not required after bariatric surgery if safety and efficacy can be effectively monitored.

IV:

  • It must be diluted before intravenous administration. The loading dose should be diluted to a maximum concentration of 20 mg/mL and administered at a maximum rate of 50 mg/minute.

Administration in Children:

IV: Note: Decrease the infusion rate if QT interval prolongation or heart block occurs; infusion should be stopped if the patient develops hypotension or QRS interval widens to >50% of baseline; rapid intravenous administration can cause severe hypotension.

Loading dose:

  • Neonates:
    • Administer for over one hour.
  • Infants, Children, and Adolescents:
    • Note: Patients should be closely monitored for the clinical response and adverse drug reactions. The rate of administration and dose should be titrated as per response and the development of adverse drug reactions.
    • Single loading dose (10 to 15 mg/kg up to 500 mg):
      • The total dose over should be given over 30 to 60 minutes
      • Note: Usual adult infusion rate: 20 to 50 mg/minute
    • Divided loading doses (2 to 6 mg/kg/dose up to 100 mg/dose):
      • Should be administered over ≥5 minutes
  • Continuous IV infusion:
    • Use an infusion pump.

The usual Infusion Concentrations in adults is 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.

 

Mechanism of action of Procainamide:

Conduction velocity and myocardial excitability are both decreased. It can also decrease myocardial contractility by increasing the electrical stimulation threshold in the ventricle, His–Purkinje system, and direct cardiac effects.

The Onset of action: 10 to 30 minutes when given IM

Protein binding: 15% to 20%

Metabolism: In the liver 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 concentration: 15 to 60 minutes when given IM

Excretion:

  • Urine (30% to 60% unchanged procainamide; 6% to 52% as NAPA)
  • Feces (<5% unchanged procainamide.

Note: More than 80% of formed NAPA is excreted through the kidneys in contrast to procainamide which is about 50% excreted via kidneys.

International Brand Names of Procainamide:

  • Biocoryl
  • Cardiorytmin
  • Gima
  • Kanide
  • Medaject Injection
  • Pasconeural-Injektopas
  • Procainamid
  • Procainamid Duriles
  • Procainamide Cloridrato
  • Procainamide Durules
  • Procainamidum
  • Procamid depot
  • Procamide
  • Pronestyl

Brand Names in Pakistan:

Brands in Pakistan will be updated later.

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