NORPACE CR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORPACE CR (NORPACE CR).
Class Ia antiarrhythmic agent; decreases myocardial excitability and conduction velocity, and prolongs refractory period by blocking sodium channels.
| Metabolism | Primarily hepatic via CYP3A4; also excreted renally. |
| Excretion | Renal (50-57% unchanged), hepatic metabolism (30-40%), fecal (<10%). Dose adjustment required for CrCl <40 mL/min. |
| Half-life | Terminal elimination half-life: 6-12 hours (normal renal function); prolonged to 12-20 hours in renal impairment. In coronary artery disease, half-life may be extended due to reduced clearance. |
| Protein binding | 30-50% bound to albumin, alpha-1-acid glycoprotein, and lipoproteins. |
| Volume of Distribution | 0.6-1.2 L/kg; larger Vd in heart failure (up to 2.0 L/kg) due to reduced tissue binding. |
| Bioavailability | Oral immediate-release: 70-80%; extended-release: 60-70% (first-pass metabolism). IV: 100%. |
| Onset of Action | Oral (immediate-release): 0.5-1.5 hours; extended-release (NORPACE CR): 2-4 hours. IV: 5-10 minutes. |
| Duration of Action | Oral immediate-release: 6-8 hours; extended-release (NORPACE CR): 12-24 hours (dosing q12h). Antiarrhythmic effect persists up to 24 hours. Note: Therapeutic effect may be prolonged in hepatic or renal dysfunction. |
Disopyramide controlled-release: 200 mg orally every 12 hours; maximum 400 mg/day.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-50 mL/min: 200 mg loading dose, then 100 mg every 12 hours. GFR 15-30 mL/min: 200 mg loading dose, then 100 mg every 24 hours. GFR <15 mL/min: 200 mg loading dose, then 100 mg every 48-72 hours. |
| Liver impairment | Child-Pugh Class B or C: Reduce dose by 50% and titrate carefully; monitor ECGs. |
| Pediatric use | Not recommended for pediatric use; safety and efficacy not established. |
| Geriatric use | Initiate at lower dose (e.g., 100 mg every 12 hours of controlled-release) due to increased risk of anticholinergic effects and renal impairment; monitor renal function and QT interval. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORPACE CR (NORPACE CR).
| Breastfeeding | Disopyramide is excreted in human breast milk; M/P ratio approximately 0.5-1.0. Limited data suggests low infant exposure but potential for hypoglycemia and bradycardia; caution advised. American Academy of Pediatrics considers disopyramide compatible with breastfeeding with monitoring. |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Evidence of teratogenicity in animal studies (increased fetal resorption and skeletal abnormalities) but no adequate human studies. Second and third trimesters: May cause fetal bradycardia, hypoglycemia, and preterm labor due to beta-blockade effects; avoid use unless benefit outweighs risk. |
■ FDA Black Box Warning
May cause widening of QRS complex and prolongation of QT interval, increasing risk of torsade de pointes and sudden death. Avoid use with other drugs that prolong QT interval. Use only for life-threatening arrhythmias.
| Serious Effects |
Pre-existing second- or third-degree AV block (unless pacemaker), cardiogenic shock, congenital QT prolongation, concurrent use of other QT-prolonging drugs, hypersensitivity to disopyramide.
| Precautions | Can worsen arrhythmias (proarrhythmic); monitor ECG, electrolytes; adjust dose in renal/hepatic impairment; avoid in patients with pre-existing QT prolongation, hypokalemia, or bradycardia. |
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| Fetal Monitoring | Monitor maternal heart rate, blood pressure, ECG, and serum disopyramide levels. Assess fetal heart rate and growth via ultrasound; monitor for signs of fetal bradycardia or hypoglycemia. Newborn should be monitored for bradycardia, hypoglycemia, and respiratory depression. |
| Fertility Effects | No specific human studies on fertility effects. Animal studies have not reported adverse effects on fertility. Disopyramide may reduce myocardial contractility and affect hemodynamic stability during labor. |