Brands, Medical Use, Clinical Data
- Tablets (100 mg, 250 mg or 500 mg)
Brands / Synonyms
Norglycin; Tolanase; Tolazamide; Tolinase; Tolinase
For use as an adjunct to diet to lower the blood glucose in patients with non-insulin dependent diabetes mellitus (Type II) whose hyperglycemia cannot be satisfactorily controlled by diet alone.
Tolazamide is an oral blood glucose lowering drug of the sulfonylurea class. Tolazamide appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which tolazamide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. Some patients who are initially responsive to oral hypoglycemic drugs, including tolazamide, may become unresponsive or poorly responsive over time. Alternatively, tolazamide may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs. In addition to its blood glucose lowering actions, tolazamide produces a mild diuresis by enhancement of renal free water clearance.
Mechanism of Action
Sulfonylureas likely bind to ATP-sensitive potassium-channel receptors on the pancreatic cell surface, reducing potassium conductance and causing depolarization of the membrane. Depolarization stimulates calcium ion influx through voltage-sensitive calcium channels, raising intracellular concentrations of calcium ions, which induces the secretion, or exocytosis, of insulin.
Rapidly and well absorbed from the gastrointestinal tract.
Overdosage of sulfonylureas can produce hypoglycemia. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization.
Biotrnasformation / Drug Metabolism
Tolazamide is metabolized to five major metabolites ranging in hypoglycemic activity from 0 to 70%.
TOLINASE Tablets are contraindicated in patients with:
1) known hypersensitivity or allergy to TOLINASE;
2) diabetic ketoacidosis, with or without coma. This condition should be treated with insulin;
3) Type I diabetes, as sole therapy.
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal
anti-inflammatory agents and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol,
probenecid, coumarins, monoamine oxidase inhibitors, and beta-adrenergic blocking agents. When such drugs are
administered to a patient receiving TOLINASE, the patient should be closely observed for hypoglycemia. When such
drugs are withdrawn from a patient receiving TOLINASE, the patient should be observed closely for loss of
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the
thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives,
phenytoin, nicotinic acid, sympa-thomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are
administered to a patient receiving TOLINASE, the patient should be closely observed for loss of control. When such
drugs are withdrawn from a patient receiving TOLINASE, the patient should be observed closely for hypoglycemia.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe
hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical or vaginal
preparations of miconazole is not known.
In a bioassay for carcinogenicity, rats and mice of both sexes were treated with tolazamide for 103
weeks at low and high doses. No evidence of car-cinogenicity was found.
Pregnancy Category C. TOLINASE, administered to pregnant rats at ten times the human dose, decreased
litter size but did not produce terato-genic effects in the offspring. In rats treated at a daily dose of 14 mg/kg no
reproductive aberrations or drug related fetal anomalies were noted. At an elevated dose of 100 mg/kg per day there
was a reduction in the number of pups born and an increased perinatal mortality. There are, however, no adequate and
well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human
response, TOLINASE is not recommended for the treatment of the pregnant diabetic patient. Serious consideration
should also be given to the possible hazards of the use of TOLINASE in women of child bearing age and in those who
might become pregnant while using the drug.
Because recent information suggests that abnormal blood glucose levels during pregnancy are
associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during
pregnancy to maintain blood glucose levels as close to normal as possible.
Prolonged severe hypoglycemia (four to ten days) has been reported in neonates born to mothers who
were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of
agents with prolonged half-lives. If TOLINASE is used during pregnancy, it should be discontinued at least two weeks
before the expected delivery date.
Although it is not known whether tolazamide is excreted in human milk, some sulfonylurea drugs are
known to be excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision
should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the
drug to the mother. If the drug is discontinued and if diet alone is inadequate for controlling blood glucose,
insulin therapy should be considered.
Safety and effectiveness in children have not been established.
Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs.
Hypoglycemia may be difficult to recognize in the elderly. The initial and maintenance dosing should be conservative
to avoid hypoglycemic reactions.
Elderly patients are prone to develop renal insufficiency, which may put them at risk of
hypoglycemia. Dose selection should include assessment of renal function.