DISOPYRAMIDE PHOSPHATE

Clinical safety rating: avoid

Positive evidence of fetus risks but benefits may outweigh risks in some cases

How it works

Class Ia antiarrhythmic agent; inhibits cardiac sodium channels, prolongs action potential duration, increases effective refractory period, and reduces myocardial excitability and conduction velocity.

What the body does with it

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.

Classification & Brands

Dosing & administration

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.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Other drugs that prolong the QT interval increase risk of torsades de pointes Can cause heart failure and severe anticholinergic side effects.

Breastfeeding	Disopyramide is excreted into breast milk with milk-to-plasma ratio of approximately 0.9. Infant exposure estimated at 2–6% of maternal weight-adjusted dose. Monitor infant for bradycardia, hypoglycemia, and apnea. Weigh benefits against potential risks.
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.

Warnings & precautions

■ 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.

Side Effect Profile

Common Effects	Anticholinergic effects (dry mouth
Serious Effects

Absolute Contraindications

["Cardiogenic shock","Pre-existing second- or third-degree AV block (without pacemaker)","Known hypersensitivity to disopyramide","Severe heart failure or left ventricular dysfunction"]

Clinical Precautions

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"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…