NORPACE CR
Clinical safety rating
cautionComprehensive clinical and safety monograph for NORPACE CR (NORPACE CR).
Comprehensive clinical and safety monograph for NORPACE CR (NORPACE CR).
Treatment of documented life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia)Off-label: prevention of atrial fibrillation recurrence, maintenance of sinus rhythm in atrial flutter
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. |
| Molecular Weight | 339.48 |
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 | Disopyramide crosses the placenta. Limited human data; animal studies show no teratogenicity but use only if clearly needed. |
| 2nd trimester | Monitor fetal heart rate; may cause uterine contractions. Use only if benefit outweighs risk. |
| 3rd trimester | May induce premature labor. Avoid near term due to potential oxytocic effect. |
Clinical note
Comprehensive clinical and safety monograph for NORPACE CR (NORPACE CR).
| Placental transfer | Crosses placenta; fetal serum levels 25-50% of maternal levels. |
| Breastfeeding | Disopyramide is excreted into breast milk; relative infant dose estimated at <10% of maternal weight-adjusted dose. Monitor infant for potential cardiac effects. |
| Lactation Rating | L3 (Moderately Safe) |
| 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. |
| 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. |
■ 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 |
Cardiogenic shockPreexisting QT prolongationSecond- or third-degree AV block (if no pacemaker)Severe uncompensated heart failure
| 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. |
| Food/Dietary | Avoid grapefruit juice as it may increase disopyramide levels. High-fat meals may delay absorption but do not significantly affect overall bioavailability; take consistently with or without food. |
| Clinical Pearls | NORPACE CR (disopyramide phosphate) is a Class Ia antiarrhythmic with strong anticholinergic effects; monitor for urinary retention, constipation, and dry mouth. It has negative inotropic effects and should be avoided in patients with compensated heart failure or cardiomyopathy. Dosage adjustment required in renal impairment (CrCl <40 mL/min). Therapeutic drug monitoring recommended (target 2-5 mcg/mL). |
| Patient Advice | Do not crush or chew extended-release tablets; swallow whole. · Take at regular 12-hour intervals to maintain steady drug levels. · Avoid driving or operating machinery until you know how this medication affects you (may cause dizziness or blurred vision). · Report signs of hypoglycemia (sweating, shakiness) in diabetic patients, as disopyramide can lower blood sugar. · Maintain adequate fluid intake to prevent constipation. · Inform all healthcare providers you are taking this medication, especially before surgery or dental procedures. |
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