TOLBUTAMIDE

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

Tolbutamide is a sulfonylurea that stimulates insulin release from the pancreatic beta cells by blocking ATP-sensitive potassium channels (K_ATP channels), leading to cell depolarization and calcium influx.

What the body does with it

Metabolism	Primarily hepatic via CYP2C9; metabolites are inactive and excreted renally.
Excretion	Renal: 75-85% as metabolites (hydroxymethyl and carboxyl derivatives), 10-20% unchanged; biliary/fecal: <5%.
Half-life	4-12 hours (mean 7 hours); clinical context: prolonged in hepatic impairment, not significantly affected by renal impairment; duration of action may be extended in hepatic disease.
Protein binding	85-97% bound to albumin.
Volume of Distribution	0.1-0.2 L/kg; low Vd indicates minimal extravascular distribution, primarily confined to plasma and extracellular fluid.
Bioavailability	Oral: approximately 85% (well absorbed); food may reduce rate but not extent.
Onset of Action	Oral: 1-2 hours; peak effect: 3-4 hours.
Duration of Action	Oral: 6-12 hours; clinical notes: shorter duration than chlorpropamide; twice-daily dosing often sufficient.

Classification & Brands

Dosing & administration

500-1000 mg orally twice daily; maximum 3000 mg/day.

Dosage form	TABLET
Renal impairment	GFR 30-60 mL/min: reduce dose by 50%; GFR <30 mL/min: contraindicated.
Liver impairment	Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use.
Pediatric use	Not recommended for children.
Geriatric use	Start with 250 mg twice daily; monitor hypoglycemia risk.

Use during pregnancy

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

Clinical note

Drugs that increase hypoglycemia risk (eg beta-blockers) Can cause severe and prolonged hypoglycemia.

Breastfeeding	Tolbutamide is excreted into breast milk in low amounts (M/P ratio approximately 0.2-0.4). Potential for hypoglycemia in the infant; caution is advised. Discontinue breastfeeding or drug based on importance to mother.
Teratogenic Risk	Tolbutamide crosses the placenta. First trimester: Risk cannot be excluded; animal studies show fetal abnormalities at high doses, but human data are limited. Second and third trimesters: May cause neonatal hypoglycemia and hyperbilirubinemia; discontinue 2-3 days before delivery to reduce risk.

Warnings & precautions

■ FDA Black Box Warning

No FDA black box warning.

Side Effect Profile

Common Effects	Hypoglycemia
Serious Effects

Absolute Contraindications

["Type 1 diabetes mellitus","Diabetic ketoacidosis","Known hypersensitivity to sulfonylureas","Severe hepatic or renal impairment"]

Clinical Precautions

Precautions

["Cardiovascular mortality risk","Hypoglycemia","Hepatic impairment","Renal impairment","Sulfonamide allergy","Hemolytic anemia in G6PD deficiency"]

Clinical Tips & Counseling

Drug interactions

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