procainamide; novacainamide (Procan Pronestyl-SR)

Introduction

Tradenames: Procan, Pronestyl-SR.

Indications

• atrial fibrillation
  • chemical cardioversion
  • preventing recurrence of atrial fibrillation
• paroxysmal supraventricular tachycardia (PSVT)
• ventricular tachycardia

Contraindications

(cautions)

• Avoid in patients with a history of torsades de pointes
• discontinue use with prolongation of QT interval
  • QTc >500 ms
  • prolongation of QTc by more than 25%
• complete heart block (2nd or 3rd degree) without pacemaker
• myasthenia gravis
• systemic lupus erythematosus

pregnancy category = c

safety in lactation = ?

Dosage

• oral
  • loading dose of 1 gram in 2 divided doses 2 hours apart
  • maintenance: 500-1000 mg PO QID or 50 mg/kg/day
  • sustained-release: 50 mg/kg or 2-4 g PO QD
• IV infusion:
  • loading dose of 1-1.5 g @ 20-30 mg/min or 15-20 mg/kg
  • 1-4 mg/min (20-80 ug/kg/min)
  • 100 mg IV every 10 min or continuous infusion @ < 20 mg/min (150 mL/hr) until:
    • QRS widens > 50%
    • dysrhythmia suppressed
    • hypotension
  • 17 mg/kg or 1 g infusion of 2g in 250 mL D5W (8 mg/mL) at 20-50 mg/min (20 mg/min stable, 50 mg/min unstable)
• intermittent IV/IM 1-6 g/day in divided doses; max 9 g/day
• decrease maintenance dose in patients with liver or renal disease
• when converting from IV to PO, continue IV for 1 hours after administration of non-sustained release tablet, 2 hours after sustained release tablet

Tabs: 250, 375, 500 mg

Sustained release: 250, 500, 750, 1000 mg

Injection: 100 mg/mL (10 mL), 500 mg/mL (2 mL)

Pharmacokinetics

• oral bioavailability is 83%
• minimal binding to plasma proteins
• metabolized by liver to N-acetylprocainamide (NAPA), an active class III antiarrhythmic agent
• 67% of the drug is excreted unchange in the urine
• clearance is variable, based on acetylator status & renal function
• elimination 1/2life
  • 3 hours with normal renal function
  • may increase to 5-20 hours in patients with renal insufficiency
• therapeutic range: 4-10 ug/mL (15-25 ug/mL for NAPA)
• moderately dialyzable: 20-50%

elimination via kidney

elimination via liver

1/2life = 2.5-5 hours

protein binding = 15 %

elimination by hemodialysis = +

Monitor

• CBC weekly for the 1st 3 months of therapy & periodically thereafter

Adverse effects

• gastrointestinal (GI)
  • nausea/vomiting
  • diarrhea
• lupus-like syndrome (30-50%)
  • fever
  • pleuropericarditis (pleural effusion)
  • hepatomegaly
  • arthralgias & myalgias
  • skin rash
  • spares kidneys
  • up to 1/3 of patients on chronic procainamide
  • may be more likely in 'slow acetylators'
  • antinuclear antibodies in 75% of patients on chronic procainamide therapy
• hemotologic
  • bone marrow suppression (0.5%)
    • agranulocytosis, neutropenia, hypoplastic anemia thrombocytopenia
  • hemolytic anemia
  • positive direct antiglobulin (Coomb's) test (DAT)
• cardiac arrhythmias
  • QT prolongation - including torsades de pointes
  • bradycardia
  • AV node block
  • asystole
  • tachycardia
  • QRS widening
• hypotension may develop with rapid IV infusion
• neurologic confusion, disorientation, hallucinations, depression, dizziness, lightheadness

• drug adverse effects of antiarrhythmic agent, Group IA

Drug interactions

• avoid other agents which prolong the QT interval
  • class Ia antiarrhythmics
  • class III antiarrhythmics
  • phenothiazines
  • tricyclic antidepressants
  • erythromycin
  • terfenadine
  • astemizole
• propranolol, amiodarone, cimetidine, ranitidine increase procainamide & NAPA levels
• quinidine & trimethoprim increase both procainamide & NAPA levels
• neuromuscular blockade of succinylcholine may be increased

• drug interaction(s) of antiarrhythmic agents in combination with diuretics

Laboratory

• specimen:
  • serum, plasma (heparin, EDTA, oxalate)
  • stable to 2 weeks at 2-8 degrees C
  • stable for 6 months at -20 degrees C
  • assay procainamide together with N-acetylprocainamide
• methods: GLC, HPLC, EIA, FPIA
• interferences: hemolysis, ichterus & lipemia may interfere with EIA & FPIA

Mechanism of action

• class Ia antiarrhythmic agent
• increases effective refractory period of:
  • the atria
  • bundle of His-Purkinje system
  • ventricles
• may decrease systemic blood pressure by causing peripheral ganglionic blockade
• weak anticholinergic activity
• slight negative inotropic activity
• its major metabolite, N-acetyl procainamide, is a class III antiarrhythmic agent

More general terms

• benzamide
• aminobenzoate
• antiarrhythmic agent, Group IA

More specific terms

• N-acetylprocainamide (NAPA, Acecainide)

Additional terms

• procainamide in serum/plasma

Database

• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4913
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=66068
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=45047
• PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=657275