DISOPYRAMIDE PHOSPHATE
Clinical safety rating
avoidPositive evidence of fetus risks but benefits may outweigh risks in some cases
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Treatment of life-threatening ventricular arrhythmias (e.g., sustained ventricular tachycardia)Suppression of symptomatic atrial fibrillation/flutter
Anticholinergic effects (dry mouth
Class Ia antiarrhythmic agent; inhibits cardiac sodium channels, prolongs action potential duration, increases effective refractory period, and reduces myocardial excitability and conduction velocity.
| Metabolism | Primarily hepatic metabolism via CYP3A4; approximately 40-60% excreted unchanged in urine. |
| Excretion | Renal excretion of unchanged drug accounts for 40-60% of elimination; hepatic metabolism (N-dealkylation) accounts for 20-30%; approximately 10-15% excreted in feces via biliary elimination. |
| Half-life | Terminal elimination half-life: 6-8 hours (normal renal function); prolonged to 15-25 hours in renal impairment (creatinine clearance <40 mL/min), requiring dose adjustment. |
| Protein binding | 50-65% bound to plasma proteins (primarily to alpha-1-acid glycoprotein, with lower affinity to albumin). |
| Volume of Distribution | 0.8-1.4 L/kg (extensive tissue distribution; higher in myocardial tissue than plasma). |
| Bioavailability | Oral: 80-90% (immediate-release); 60-80% (sustained-release due to incomplete absorption). |
| Onset of Action | Oral: 0.5-3 hours; Intravenous: 5-15 minutes (after loading dose). |
| Duration of Action | Oral: 6-12 hours (sustained-release formulation 12 hours); Intravenous: 3-6 hours dependent on dose. |
| Molecular Weight | 339.47 |
100-200 mg orally every 6 hours; immediate-release: 100-200 mg every 6 hours; extended-release: 200-300 mg every 12 hours.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: 100 mg every 8-12 hours; GFR 15-29 mL/min: 100 mg every 12-24 hours; GFR <15 mL/min or dialysis: 100 mg every 24 hours or 50 mg every 12 hours. |
| Liver impairment | Child-Pugh class B: reduce dose by 50%; Child-Pugh class C: avoid use or reduce by 75%. |
| Pediatric use | Children <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; adolescents: same as adult dosing up to 400 mg/day. |
| Geriatric use | Start at low end of dosing range (100 mg every 6 hours) due to decreased renal function and increased sensitivity; monitor QTc interval and anticholinergic effects. |
| 1st trimester | Animal studies have shown teratogenic effects; no adequate human studies. Risk cannot be ruled out. Use only if potential benefit justifies potential risk. |
| 2nd trimester | May cause uterine contractions due to oxytocic properties; use with caution. |
| 3rd trimester | May cause premature labor or uterine hyperstimulation; avoid in late pregnancy. |
Clinical note
Other drugs that prolong the QT interval increase risk of torsades de pointes Can cause heart failure and severe anticholinergic side effects.
| Placental transfer | Crosses the placenta; fetal plasma levels approximately 10-40% of maternal levels. |
| Breastfeeding | Excreted into breast milk in small amounts; potential for serious adverse reactions in nursing infants, including cardiovascular effects. Use with caution, monitor infant for bradycardia and hypotension. |
| Lactation Rating | L3 - Moderately Safe |
| Teratogenic Risk | Disopyramide crosses the placenta. First trimester: No well-controlled studies; potential for adverse effects based on animal data. Second and third trimesters: May stimulate uterine contractions, potentially causing preterm labor; reports of neonatal hypoglycemia and respiratory depression. Not recommended during pregnancy unless benefit outweighs risk. |
| Fetal Monitoring | Maternal: ECG, serum potassium, liver/renal function, blood pressure, heart rate. Fetal: Ultrasound for growth and amniotic fluid volume, fetal heart rate monitoring for signs of distress or preterm labor. |
| Fertility Effects | No well-controlled studies; animal studies show no significant impact on fertility. Potential for anticholinergic effects may theoretically affect reproductive function, but clinical significance unclear. |
■ FDA Black Box Warning
Disopyramide has negative inotropic effects and may precipitate or exacerbate heart failure. Use with caution in patients with pre-existing heart failure or significant left ventricular dysfunction.
| Common Effects | Anticholinergic effects (dry mouth |
| Serious Effects |
Cardiogenic shockPre-existing second- or third-degree AV block (unless pacemaker)Known hypersensitivity to disopyramideLong QT syndromeSevere uncompensated heart failureGlaucomaUrinary retention
| Precautions | May worsen or precipitate heart failure due to negative inotropy, Risk of proarrhythmia (e.g., torsades de pointes) especially with hypokalemia or bradycardia, Anticholinergic effects: urinary retention, dry mouth, blurred vision, constipation, May cause hypoglycemia in rare cases, Dose adjustment required in renal or hepatic impairment |
| Food/Dietary | Avoid grapefruit juice as it may increase disopyramide concentrations. Limit caffeine intake as it may worsen arrhythmias. Avoid high-fat meals as they may reduce absorption. |
| Clinical Pearls | Disopyramide is a class IA antiarrhythmic with significant negative inotropic and anticholinergic effects. Avoid in patients with heart failure, cardiogenic shock, or glaucoma. Dose adjustment required in renal impairment. Monitor QRS and QT intervals; proarrhythmia risk. May cause hypoglycemia in elderly or diabetic patients. Therapeutic drug monitoring recommended (target 2-5 mcg/mL). |
| Patient Advice | Take exactly as prescribed; do not skip doses or double up. · Do not take with grapefruit juice. · Avoid alcohol and other CNS depressants. · Report symptoms of heart failure (shortness of breath, swelling) or arrhythmia (palpitations, syncope). · May cause dry mouth, blurred vision, urinary retention; use caution driving. · Monitor blood sugar if diabetic. · Do not stop abruptly without consulting your doctor. |
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