Skip to Content


Pronunciation: tole-BYOO-tuh-mide
Class: Sulfonylurea

Trade Names:
- Tablets 500 mg

Trade Names:
Orinase Diagnostic
- Powder for injection 1 g (as sodium)/vial

Apo-Tolbutamide (Canada)


Decreases blood glucose by stimulating release of insulin from pancreas.



Orally administered tolbutamide is readily absorbed from the GI tract.


Tolbutamide has no p-amino group, cannot be acetylated; however, presence of p-methyl group makes it susceptible to oxidation. A major metabolite is 1-butyl-3-p-carboxy-phenylsulfonylurea (inactive).


Tolbutamide t ½ is 4.5 to 6.5 h.


Onset of action is 20 min.


Time to peak effect is 3 to 4 h.


Tolbutamide duration of action is 24 h.

Indications and Usage

Oral form

Adjunct to diet to lower blood glucose in patients with non-insulin-dependent diabetes mellitus (type 2) whose hyperglycemia cannot be controlled by diet alone.

IV form (tolbutamide sodium)

Aid in diagnosis of pancreatic islet cell adenoma.


Hypersensitivity to sulfonylureas; diabetes complicated by ketoacidosis with or without coma; sole therapy of insulin-dependent (type 1) diabetes mellitus; diabetes occurring during pregnancy.

Dosage and Administration


PO Usually 1 to 2 g/day (range, 0.25 to 3 g) in 1 to 2 divided doses.

For Diagnostic Purposes

IV 1 g over 2 to 3 min.

Drug Interactions

Androgens, anticoagulants, azole antifungals, chloramphenicol, clofibrate, dicumarol, fenfluramine, fluconazole, gemfibrozil, histamine H 2 antagonists, magnesium salts, methyldopa, MAOIs, phenylbutazone, probenecid, salicylates, sulfinpyrazone, sulfonamides, tricyclic antidepressants, urinary acidifiers

May increase hypoglycemic effect.

Beta-blockers, calcium channel blockers, cholestyramine, corticosteroids, diazoxide, estrogens, hydantoins, isoniazid, nicotinic acid, oral contraceptives, phenothiazines, rifampin, sympathomimetics, thiazide diuretics, thyroid agents, urinary alkalinizers

May decrease hypoglycemic effect.


Charcoal can reduce the absorption of sulfonylureas; depending on the clinical situation, this will reduce their efficacy or toxicity.

Digitalis glycosides

Coadministration may result in increased digitalis serum levels.


May cause increased digoxin serum concentrations.


May cause disulfiram-like reaction.

Laboratory Test Interactions

Drug may cause false-positive reaction for albumin with acidification-after-boiling test; no interference occurs with sulfosalicyclic acid test. Elevated LFTs and elevations in BUN and creatinine may occur.

Adverse Reactions


Increased risk of cardiovascular mortality.


Dizziness; vertigo.


Allergic skin reactions; eczema; pruritus; erythema; urticaria; morbilliform or maculopapular eruptions; lichenoid reactions; porphyria; photosensitivity.




Nausea; epigastric fullness; heartburn.


Leukopenia; thrombocytopenia; aplastic anemia; agranulocytosis; hemolytic anemia; pancytopenia.


Cholestatic jaundice.


Hypoglycemia; SIADH with water retention and dilutional hyponatremia, especially in patients with CHF or hepatic cirrhosis.


Disulfiram-like reaction; weakness; paresthesia; fatigue; malaise; slight burning sensation along course of vein during IV injection; thrombophlebitis with thrombosis of injected vein.



Category C . Insulin is recommended to control elevated blood glucose levels during pregnancy.


Excreted into breast milk.


Safety and efficacy have not been established.


Particularly susceptible to hypoglycemic action. Hypoglycemia may be difficult to recognize in elderly.

Renal Function

Use drug with caution.

Hepatic Function

Use drug with caution.

Disulfiram-like syndrome

Administration of drug with alcohol may induce facial flushing and breathlessness.

Cardiovascular risk

Patients treated for 5 to 8 yr with diet plus tolbutamide (1.5 g/day) had a rate of cardiovascular mortality approximately 2.5 times that of patients treated with diet alone.



Hypoglycemia including symptoms of the following: tingling of lips and tongue, nausea, lethargy, confusion, agitation, nervousness, tachycardia, sweating, tremor, hunger, convulsions, stupor, coma.

Patient Information

  • Instruct patient to follow the diet and exercise regimen prescribed by health care provider.
  • Inform patient of symptoms of and treatment for low blood sugar and advise patient to carry source of sugar at all times.
  • Instruct patient to avoid alcohol. Inform patient that alcohol may react with tolbutamide and cause Antabuse -like reaction (eg, flushing, headache, dizziness, high BP).
  • Instruct patient to monitor weight and to inform health care provider if steady weight gain occurs.
  • Inform patient that surgery, illness, or trauma may require temporary use of insulin.
  • Instruct patient to alert health care provider to following problems: nausea, vomiting, GI distress, diarrhea, fever, sore throat, rash, itching, weakness, unusual bruising or bleeding, spilling of glucose or ketones in urine.
  • Caution patient to avoid exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
  • Recommended that patient carry medical identification (eg, card, bracelet) indicating condition and drug therapy.

Copyright © 2009 Wolters Kluwer Health.