Glyburide

Glyburide is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

of oral sulfonylurea hypoglycemic drugs. In addition to its blood glucose lowering actions, Glyburide produces a mild diuresis by enhancement of renal free water clearance. Clinical experience to date indicates an extremely low incidence of disulfiram-like reactions in patients while taking Glyburide. Pharmacokinetics Single-dose studies with Glyburide in normal subjects demonstrate significant absorption within 1 hour, peak drug levels at about 4 hours, and low but detectable levels at 24 hours. Mean serum levels of glyburide, as reflected by areas under the serum concentration-time curve, increase in proportion to corresponding increases in dose. Multiple-dose studies with Glyburide in diabetic patients demonstrate drug level concentration-time curves similar to single-dose studies, indicating no build-up of drug in tissue depots.

There is no fixed dosage regimen for the management of diabetes mellitus with Glyburide or any other hypoglycemic agent. The patient's fasting blood glucose must be measured periodically to determine the minimum effective dose for the patient, to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication, and to detect secondary failure, i.e., loss of adequate blood glucose lowering response after an initial period of effectiveness. Periodic glycosylated hemoglobin determinations should be performed. Short-term administration of Glyburide may be sufficient during periods of transient loss of control in patients usually controlled well on diet. 1. Usual Starting Dose The usual starting dose of Glyburide as initial therapy is 2.5 to 5 mg daily, administered with breakfast or the first main meal.

Glyburide is contraindicated in patients: With known hypersensitivity to the drug or any of its excipients. With type 1 diabetes mellitus or diabetic ketoacidosis, with or without coma. These conditions should be treated with insulin. Treated with bosentan.

SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups ( Diabetes 19 (supp. 2): 747–830, 1970). UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2-1/2 times that of patients treated with diet alone.

Hypoglycemia See PRECAUTIONS and OVERDOSAGE Sections. Gastrointestinal Reactions Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure, Glyburide should be discontinued if this occurs. Liver function abnormalities, including isolated transaminase elevations, have been reported. Gastrointestinal disturbances, e.g., nausea, epigastric fullness, and heartburn, are the most common reactions and occur in 1.8% of treated patients. They tend to be dose-related and may disappear when dosage is reduced. Dermatologic Reactions Allergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions, occur in 1.5% of treated patients. These may be transient and may disappear despite continued use of Glyburide. Bullous reactions, erythema multiforme, and exfoliative dermatitis, have been reported.

The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, ACE inhibitors, disopyramide, fluoxetine, clarithromycin, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving Glyburide, the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving Glyburide, the patient should be observed closely for loss of control. An increased incidence of elevated liver enzymes was observed in patients receiving glyburide concomitantly with bosentan. Therefore concomitant administration of glyburide and bosentan is contraindicated.

Store at 25°C (77°F), excursions permitted to 15–30°C (59–86°F).