PRONESTYL-SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PRONESTYL-SR (PRONESTYL-SR).
Class Ia antiarrhythmic agent; blocks sodium channels, slowing phase 0 depolarization and decreasing myocardial excitability; also prolongs refractory period and has anticholinergic effects.
| Metabolism | Extensively metabolized in the liver by N-acetyltransferase (NAT2) to N-acetylprocainamide (NAPA), an active metabolite; also undergoes hydrolysis. |
| Excretion | Renal excretion: ~50-60% unchanged drug (procainamide), ~15-30% as N-acetylprocainamide (NAPA). Biliary/fecal: minor (<5%). |
| Half-life | 2.5-4.7 hours (procainamide); 6-9 hours (NAPA, active metabolite). Prolonged in renal impairment (up to 11-20 hours for procainamide, 30-42 hours for NAPA). |
| Protein binding | 15-20% primarily to albumin; NAPA binding ~10%. |
| Volume of Distribution | 1.7-2.5 L/kg (procainamide); 1.2-1.6 L/kg (NAPA). Refers to extensive tissue distribution. |
| Bioavailability | Oral (immediate): ~75-95%; Oral (SR): ~75-95% (but slower absorption); IM: nearly 100%. |
| Onset of Action | Oral (SR): 30-90 minutes; IV: 5-10 minutes; IM: 10-30 minutes. |
| Duration of Action | Oral (SR): 6-8 hours (sustained release formulation); IV: 3-4 hours; IM: 4-6 hours. Note: Duration correlates with serum concentrations; monitor for toxicity. |
500–1000 mg orally every 6 hours (sustained-release). Maximum 1.5 g per dose or 4 g per day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl >50 mL/min: 100% dose; CrCl 10–50 mL/min: 50–75% dose; CrCl <10 mL/min: 25–50% dose. |
| Liver impairment | Child-Pugh A: 100% dose; Child-Pugh B: 75% dose; Child-Pugh C: 50% dose. |
| Pediatric use | 12.5–25 mg/kg/day orally divided every 6 hours (sustained-release not recommended in children). |
| Geriatric use | Initiate at 500 mg orally every 12 hours; titrate slowly; monitor for hypotension and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PRONESTYL-SR (PRONESTYL-SR).
| Breastfeeding | Small amounts excreted into breast milk; M/P ratio ~0.26. Consider infant monitoring for bradycardia and rash. Use with caution, especially in preterm neonates. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: No well-controlled studies; potential for fetal bradycardia and hypotension. Second and third trimesters: May cause fetal bradycardia, QT prolongation, and arrhythmias. Avoid use unless benefit outweighs risk. |
| Fetal Monitoring |
■ FDA Black Box Warning
May cause agranulocytosis, leukopenia, thrombocytopenia, and other blood dyscrasias; use only for life-threatening arrhythmias.
| Serious Effects |
Hypersensitivity; complete heart block; torsades de pointes; myasthenia gravis; pre-existing QT prolongation; concurrent use with other Class Ia agents.
| Precautions | Proarrhythmic effects; lupus erythematosus-like syndrome; blood dyscrasias; QT prolongation; heart failure; renal impairment (dose adjustment required); liver disease; and drug interactions with other antiarrhythmics. |
Loading safety data…
| Maternal: ECG, heart rate, blood pressure, procainamide and NAPA levels, renal function. Fetal: Heart rate monitoring via nonstress test or biophysical profile if used near term. |
| Fertility Effects | No human data on fertility impairment. Animal studies show no adverse effects on reproduction; theoretical risk from systemic effects. |