Procainamide

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Contents 1 Mechanism of action 2 Therapeutic uses 3 Dose 3.1 Intravenous for acute arrhythmias 3.2 Oral 4 Contraindications 5 Side effects 6 Drug interactions (not inclusive) 7 Comments 8 Monitor 9 Pharmacokinetics

Mechanism of action

• Inhibit fast sodium channels depressing phase 0 of the action potential
• Class Ia agents also have limited Class III activity
• Can prolong the QT Interval increasing the risk of Torsades de Pointes

Therapeutic uses

• Atrial arrhythmias
• Ventricular arrhythmias

Dose

Intravenous for acute arrhythmias

• Loading dose
  • 15 - 17 mg/kg infuse at 20-30 mg/min
  • Infusion rates of up to 50 mg/min may be used; however may induce hypotension
• Maintenance dose
  • 1 - 4 mg/min
  • Adjust dose in renal dysfunction

Oral

• Immediate-release capsules or tablets 250 – 500 mg/dose every 3-6 hours
• Sustained-released tablets 250 750 mg every 6 hours
• Long-acting tablets 1000 – 2000 mg every 12 hours
• Dose dependent on renal function and blood levels

Contraindications

• Complete Heart Block,Second Degree AV Block or Third Degree AV Block
• Hypersensitivity to Procainamide, procaine, or other ester-type local anesthetics
• Systemic Lupus Erythematosus
• Torsades de Pointes

Side effects

• Drug-induced Systemic Lupus Erythematosus
  • 50 - 80% of patients develop a positive antinuclear antibodies (ANA) while on procainamide
  • 30 - 50% of those who develop a positive ANA will develop drug induced Systemic Lupus Erythematosus
  • Patients who are slow acetylators are at a higher risk of developing a positive ANA and Systemic Lupus Erythematosus
  • Patients will typically complain of Rash, Arthralgias, Fever, Pericarditis and Pleuritis
  • The symptoms resolve within 2 weeks of stopping procainamide
• Hypotension may occur during IV administration and usually during the loading phase. Slowing the infusion rate decreases hypotension
• Nausea and diarrhea
• QT Prolongation -> may lead to Torsades de Pointes
• Rare cases of agranulocytosis, neutropenia, or thrombocytopenia can be life threatening and must be monitored

Drug interactions (not inclusive)

• Amiodarone
• Cimetidine
• Ofloxacin (other quinolones as well)
• Ranitidine
• Trimethoprim
• Cisapride
• Neuromuscular blocking agents
• Medications that prolong QT interval

Comments

• Procainamide may increase AV nodal conduction in patients with Atrial Fibrillation or Atrial Flutter therefore, the AV node should be blocked (e.g., with beta blockers, calcium channel blockers, digitalis) before initiating procainamide for these indications unless patient has Wolf-Parkinson-White Syndrome

Monitor

• ECG daily for the first 2 - 4 days for QT, QRS, and PR prolongation
• Periodically white blood cell count for agranulocytosis
• Patient for drug-induced systemic lupus erythematosus

Pharmacokinetics

• Half-life
  • Procainamide: 2.5-4.5 hours
  • N-acetylprocainamide (NAPA): 4-15 hours (7 hours average)

Elimination:

• Procainamide 50% renal and 50% hepatic metabolism
  • N-acetylprocainamide > 80% renal
  • Formation of N-acetylprocainamide is dependent on acetylator phenotype (i.e., fast or slow acetylators)
• Therapeutic range
  • Procainamide 4 - 10 mg/l
  • N-acetylprocainamide < 20 mg/l