CHLORPROPAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CHLORPROPAMIDE (CHLORPROPAMIDE).

How it works

Stimulates insulin release from pancreatic beta cells by blocking ATP-sensitive potassium channels, increasing intracellular calcium, and enhancing peripheral insulin sensitivity. Also reduces hepatic glucose production.

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9; 80-90% excreted renally as unchanged drug and metabolites.
Excretion	Renal excretion of unchanged drug (80-90%) and hepatic metabolites (10-20%). Biliary/fecal excretion is minimal (<5%).
Half-life	36 hours (range 25-60 hours). Prolonged in renal impairment due to cumulative effects and hypoglycemia risk.
Protein binding	60-90% bound to albumin.
Volume of Distribution	0.13-0.24 L/kg. Reflects modest distribution primarily in extracellular fluid.
Bioavailability	100% (oral).
Onset of Action	Oral: 1 hour for reduction in blood glucose; peak effect at 4-6 hours.
Duration of Action	24-72 hours. Long duration due to slow elimination; once-daily dosing. Risk of prolonged hypoglycemia.

Classification & Brands

Dosing & administration

Initial: 250 mg orally once daily. Maintenance: 100-500 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: reduce dose by 50%; eGFR <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: consider dose reduction; Child-Pugh C: contraindicated.
Pediatric use	Not recommended for use in pediatric patients.
Geriatric use	Start at 100 mg orally once daily; avoid in patients >65 years due to prolonged half-life and risk of hypoglycemia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CHLORPROPAMIDE (CHLORPROPAMIDE).

Breastfeeding	Chlorpropamide is excreted into breast milk. M/P ratio unknown. Due to risk of neonatal hypoglycemia, breastfeeding is contraindicated.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Associated with increased risk of congenital anomalies, including cardiovascular and neural tube defects. Second and third trimesters: Risk of prolonged neonatal hypoglycemia and macrosomia. Avoid use; insulin preferred.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased risk of cardiovascular mortality compared to diet alone or diet plus insulin, based on the University Group Diabetes Program (UGDP) study.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Severe renal impairment (CrCl < 50 mL/min)","Severe hepatic impairment","Hypersensitivity to sulfonylureas","Pregnancy and lactation"]

Clinical Precautions

Precautions

["Hypoglycemia risk, especially in elderly, debilitated, or malnourished patients; renal or hepatic insufficiency; alcohol use.","Prolonged half-life (36 hours) increases hypoglycemia duration.","Disulfiram-like reaction with alcohol.","SIADH-like syndrome (hyponatremia) due to ADH potentiation.","Hepatic porphyria risk.","May cause cholestatic jaundice, agranulocytosis, or aplastic anemia."]

Clinical Tips & Counseling

Drug interactions

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CHLORPROPAMIDE

Clinical safety rating: caution

Comprehensive clinical and safety monograph for CHLORPROPAMIDE (CHLORPROPAMIDE).

How it works

What the body does with it

Metabolism	Hepatic metabolism via CYP2C9; 80-90% excreted renally as unchanged drug and metabolites.
Excretion	Renal excretion of unchanged drug (80-90%) and hepatic metabolites (10-20%). Biliary/fecal excretion is minimal (<5%).
Half-life	36 hours (range 25-60 hours). Prolonged in renal impairment due to cumulative effects and hypoglycemia risk.
Protein binding	60-90% bound to albumin.
Volume of Distribution	0.13-0.24 L/kg. Reflects modest distribution primarily in extracellular fluid.
Bioavailability	100% (oral).
Onset of Action	Oral: 1 hour for reduction in blood glucose; peak effect at 4-6 hours.
Duration of Action	24-72 hours. Long duration due to slow elimination; once-daily dosing. Risk of prolonged hypoglycemia.

Classification & Brands

Dosing & administration

Initial: 250 mg orally once daily. Maintenance: 100-500 mg orally once daily.

Dosage form	TABLET
Renal impairment	eGFR 30-60 mL/min: reduce dose by 50%; eGFR <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: consider dose reduction; Child-Pugh C: contraindicated.
Pediatric use	Not recommended for use in pediatric patients.
Geriatric use	Start at 100 mg orally once daily; avoid in patients >65 years due to prolonged half-life and risk of hypoglycemia.

Use during pregnancy

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

Clinical note

Comprehensive clinical and safety monograph for CHLORPROPAMIDE (CHLORPROPAMIDE).

Breastfeeding	Chlorpropamide is excreted into breast milk. M/P ratio unknown. Due to risk of neonatal hypoglycemia, breastfeeding is contraindicated.
Teratogenic Risk	FDA Pregnancy Category D. First trimester: Associated with increased risk of congenital anomalies, including cardiovascular and neural tube defects. Second and third trimesters: Risk of prolonged neonatal hypoglycemia and macrosomia. Avoid use; insulin preferred.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Increased risk of cardiovascular mortality compared to diet alone or diet plus insulin, based on the University Group Diabetes Program (UGDP) study.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Severe renal impairment (CrCl < 50 mL/min)","Severe hepatic impairment","Hypersensitivity to sulfonylureas","Pregnancy and lactation"]