NORPACE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORPACE (NORPACE).
Class Ic antiarrhythmic agent; blocks voltage-gated sodium channels, slowing conduction velocity and prolonging refractory periods in cardiac tissue.
| Metabolism | Extensively metabolized in the liver primarily by CYP2D6; also involves CYP1A2 and CYP3A4 to a minor extent. Active metabolite: desethylnorpace. |
| Excretion | Renal: 40-60% unchanged; biliary/fecal: minor (10-20%). |
| Half-life | Terminal elimination half-life: 6-8 hours (normal renal function); prolonged in renal impairment (up to 24 hours). |
| Protein binding | 80-90%, primarily to alpha-1-acid glycoprotein and albumin. |
| Volume of Distribution | 1.8-3.6 L/kg; large, indicating extensive tissue distribution. |
| Bioavailability | Oral: 80-90%. |
| Onset of Action | Oral: 1-3 hours; IV: 5-10 minutes. |
| Duration of Action | Oral: 6-8 hours; IV: 2-4 hours for antiarrhythmic effect; dose-dependent. |
150 mg orally every 6 hours (maximum 300 mg per dose), extended-release formulation 300 mg every 12 hours.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: 150 mg every 12-24 hours; GFR 15-29 mL/min: 150 mg every 24-48 hours; GFR <15 mL/min (not on dialysis): 150 mg every 48 hours or 100 mg every 24 hours. |
| Liver impairment | Child-Pugh Class A: no adjustment; Child-Pugh Class B: reduce dose by 25-50% with monitoring; Child-Pugh Class C: contraindicated or use with extreme caution. |
| Pediatric use | <1 year: 10-30 mg/kg/day divided every 6 hours; 1-4 years: 10-30 mg/kg/day divided every 6 hours; 4-12 years: 10-30 mg/kg/day divided every 6 hours; 12-18 years: 150-300 mg every 6 hours. Maximum 800 mg/day. |
| Geriatric use | Initiate at 100 mg every 6 hours; consider lower doses due to age-related renal decline; monitor for anticholinergic effects and QT prolongation. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORPACE (NORPACE).
| Breastfeeding | Disopyramide is excreted in breast milk with an M/P ratio of approximately 1:1.1. The relative infant dose is about 2–10% of the maternal weight-adjusted dose. Monitor infant for bradycardia, QT changes, and hypoglycemia. Alternative agents preferred unless benefit outweighs risk. |
| Teratogenic Risk | First trimester: No evidence of increased risk of congenital malformations in human studies, but animal studies are insufficient. Second and third trimesters: Risk of fetal bradycardia, QT prolongation, and neonatal depression at delivery. Disopyramide may stimulate uterine contractions, increasing risk of preterm labor. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pre-existing second- or third-degree AV block unless pacemaker is present","Cardiogenic shock","Severe heart failure","QTc interval > 450 ms","Concomitant use of other QT-prolonging drugs","Hypersensitivity to disopyramide or any component"]
| Precautions | ["Proarrhythmic effects (e.g., new or worsened arrhythmias, torsades de pointes)","Heart failure exacerbation","Hepatic impairment","Renal impairment","Electrolyte disturbances (hypokalemia, hypomagnesemia)","Conduction disturbances (e.g., QT prolongation, heart block)"] |
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| Fetal Monitoring | Maternal: ECG monitoring for QT prolongation, arrhythmias, and signs of heart failure. Fetal: Ultrasound for growth, heart rate monitoring for bradycardia, and postnatal ECG in neonate if maternal exposure in third trimester. |
| Fertility Effects | No known significant impact on fertility in humans. Animal studies show no impairment of fertility at clinically relevant doses. |