tolbutamide
Orinase

Available forms
Available by prescription only
Tablets: 500 mg

Indications and dosages
 Adjunct to diet to lower blood glucose levels in patients with type 2 diabetes. Adults: Initially, 1 to 2 g P.O. daily as single dose or divided b.i.d. or t.i.d. May adjust dosage to maximum of 3 g P.O. daily.

Pharmacodynamics
Antidiabetic action: Tolbutamide lowers blood glucose levels by stimulating insulin release from functioning beta cells of the pancreas. After prolonged administration, the hypoglycemic effects of the drug appear to reflect extrapancreatic effects, possibly including reduction of basal hepatic glucose production and enhanced peripheral sensitivity to insulin.

Pharmacokinetics
Absorption: Absorbed readily from the GI tract.
Distribution: Probably distributed into extracellular fluid. Drug is 95% bound to plasma proteins.
Metabolism: Metabolized in the liver to inactive metabolites.
Excretion: Drug and its metabolites are excreted in urine and feces. Half-life is 4 1/2 to 6 1/2 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or other sulfonylureas; pregnant women; breast-feeding women; patients with type 1 diabetes or diabetes that can be adequately controlled by diet; patients with type 2 diabetes complicated by fever, ketosis, acidosis, coma, or other acute complications such as major surgery, severe infection, or severe trauma; and patients with severe renal insufficiency.
  Use cautiously in elderly, debilitated, or malnourished patients and in those with impaired renal or hepatic function or porphyria.

Interactions
Drug-drug. Anticoagulants: Increases hypoglycemic activity; enhances anticoagulant effect. Monitor blood glucose levels, PT, and INR. Dosage may need adjustment.
Beta blockers, including ophthalmics: Masks symptoms of hypoglycemia and may prolong hypoglycemia. Use together cautiously.
Calcium channel blockers, corticosteroids, estrogens, hormonal contraceptives, isoniazid, phenothiazines, phenytoin, sympathomimetics, thiazide diuretics, thyroid products, triamterene: Decreases hypoglycemic effect. Monitor blood glucose level; dosage may need adjustment.
Chloramphenicol, insulin, MAO inhibitors, NSAIDs, probenecid, salicylates, sulfonamides: Increases hypoglycemic effect. Monitor blood glucose levels closely.
Drug-herb. Aloe, bitter melon, bilberry leaf, burdock, dandelion, fenugreek, garlic, ginseng: May improve blood glucose control. A reduction of antidiabetic dosage may be needed.
Drug-lifestyle. Alcohol use: May produce a disulfiram-like reaction, with nausea, vomiting, abdominal cramps, and headaches. Discourage alcohol use.

Adverse reactions
CNS: headache.
GI: taste alterations, nausea, heartburn, epigastric distress.
Hematologic: leukopenia, hemolytic anemia, thrombocytopenia, aplastic anemia, agranulocytosis, pancytopenia.
Hepatic: hepatic porphyria.
Metabolic: hypoglycemia, dilutional hyponatremia.
Skin: rash, pruritus, erythema, urticaria.
Other: SIADH, hypersensitivity reactions,disulfiram-like reactions.

Effects on lab test results
• May decrease sodium and glucose levels.
• May decrease hemoglobin and WBC, RBC, platelet, and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include low blood glucose levels, tingling of lips and tongue, hunger, nausea, decreased cerebral function (lethargy, yawning, confusion, agitation, nervousness), increased sympathetic activity (tachycardia, sweating, tremor), and ultimately, seizures, stupor, and coma.
 Mild hypoglycemia, without loss of consciousness or neurologic findings, responds to treatment with oral glucose and dose adjustments. If patient loses consciousness or develops neurologic findings, the patient should receive rapid injection of D₅₀W, followed by a continuous infusion of D₁₀W at a rate to maintain blood glucose levels greater than 100 mg/dl. Monitor patient for 24 to 48 hours.

Special considerations
• To avoid GI intolerance for those patients on larger doses and to improve control of hyperglycemia, divided doses given before the morning and evening meals are recommended.
• Patients should avoid taking tolbutamide at bedtime because of the potential for nocturnal hypoglycemia.
• To change from insulin to oral therapy with tolbutamide, if insulin dose is less than 20 units daily, insulin may be stopped and oral therapy started at 1 to 2 g daily. If insulin dose is 20 to 40 units daily, insulin dose is reduced 30% to 50% and oral therapy started as above. If insulin dose is more than 40 units daily, insulin dose is decreased 20% and oral therapy started as above. Further reductions in insulin dose are based on patient’s response to oral therapy.
• When substituting tolbutamide for chlorpropamide therapy, monitor patient closely for the first 2 weeks because of prolonged retention of chlorpropamide in the body, which may result in hypoglycemia.
• Tolbutamide may give a false-positive reading for albumin in urine if measured by the acidification-after-boiling test. There’s no interference with the sulfosalicylic acid test. Tolbutamide decreases the uptake of radioactive iodine and may interfere with test results of radioactive iodine uptake.
Pregnant patients
• Use cautiously in women of childbearing age. Tolbutamide is contraindicated for treatment of diabetes related to pregnancy.
Breast-feeding patients
• Tolbutamide appears in breast milk. Because of the risk of hypoglycemia in the breast-fed infant, a decision should be made to discontinue either drug or breast-feeding.
Pediatric patients
• Tolbutamide is ineffective in type 1 diabetes. Safety and efficacy in children haven’t been established.
Geriatric patients
• These patients may be more sensitive to the effects of drug because of reduced metabolism and elimination.
• Hypoglycemia causes more neurologic symptoms in these patients.
• Elderly patients usually require a lower initial dose.

Patient education
• Emphasize to patient the importance of following prescribed diet, exercise, and medical regimen.
• Instruct patient to take drug at the same time each day.
• Inform patient that, if a dose is missed, it should be taken immediately, unless it’s almost time to take the next dose. Tell patient not to double the doses.
• Advise patient to avoid products containing alcohol while taking tolbutamide because of prolonged hypoglycemic effect.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use