Sulfonylureas (second-generation)-Glyburide

Brand name
Diabeta   Micronase
class-Sulfonylureas (second-generation)-Raise the amount of insulin in the body 
Description
Glyburide tablets (micronized) contain smaller particle size, glyburide. Glyburide is an oral blood-glucose-lowering drug of the sulfonylurea class. Glyburide is a white, crystalline compound.Each tablet, for oral administration, contains 1.5 mg, 3 mg or 6 mg of micronized glyburide. In addition, each tablet contains the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, pregelatinized starch, and sodium lauryl sulfate. In addition, the 3 mg tablets contain the following ingredient: D&C Yellow #10 Aluminum Lake and the 6 mg tablets contain the following ingredients: D&C Yellow #10 Aluminum Lake and FD&C Blue #1 Aluminum Lake.The chemical name for glyburide is 1-[[p-[2-(5-Chloro-o-anisamido) ethyl]phenyl]-sulfonyl]-3-cyclohexylurea and the molecular weight is 494.01.  
 Clinical Pharmacology
 mechanism of Actions
Glyburide 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 glyburide 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. The combination of glyburide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complimentary mechanisms.In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Disulfiram-like reactions have very rarely been reported in patients treated with glyburide.
Pharmacokinetics
Single dose studies with glyburide tablets (micronized) in normal subjects demonstrate significant absorption of glyburide within one hour, peak drug levels at about two to three hours, and low but detectable levels at twenty-four hours.Bioavailability studies have demonstrated that micronized glyburide tablets 3 mg provide serum glyburide concentrations that are not bioequivalent to those from non-micronized glyburide tablets 5 mg. Therefore, the patient should be retitrated.It has been reported that in a single-dose bioavailability study  in which subjects received micronized glyburide tablets 3 mg and non-micronized glyburide tablets 5 mg with breakfast, the peak of the mean serum glyburide concentration-time curve was 97.2 ng/mL for the micronized glyburide tablets 3 mg and 87.5 ng/mL for non-micronized glyburide tablets 5 mg. The mean of the individual maximum serum concentration values of glyburide (Cmax) from micronized glyburide tablets 3 mg was 106 ng/mL and that from non-micronized glyburide tablets was 104 ng/mL. The mean glyburide area under the serum concentration-time curve (AUC) for this study was 568 ng × hr/mL for micronized glyburide tablets 3 mg and 746 ng × hr/mL for non-micronized glyburide tablets 5 mg.
  Indications And Usage
Glyburide tablets (micronized) are indicated 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.Glyburide may be used concomitantly with metformin when diet and glyburide or diet and metformin alone do not result in adequate glycemic control (see metformin).In initiating treatment for non-insulin-dependent diabetes, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The importance of regular physical activity should also be stressed, and cardiovascular risk factors should be identified and corrective measures taken where possible. If this treatment program fails to reduce symptoms and/or blood glucose, the use of an oral sulfonylurea or insulin should be considered. Use of glyburide must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitution or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of glyburide. 
Contraindications
Glyburide is contraindicated in patients with:
 Known hypersensitivity or allergy to the drug.
Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
 Type I diabetes mellitus, as sole therapy.
 Adverse Reactions
Gastrointestinal ReactionsCholestatic jaundice and hepatitis may occur rarely; 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, having occurred in 1.8% of treated patients during clinical trials. They tend to be dose related and may disappear when dosage is reduced.
Dermatologic ReactionsAllergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions occurred in 1.5% of treated patients during clinical trials. These may be transient and may disappear despite continued use of glyburide. If skin reactions persist, the drug should be discontinued.Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
Hematologic ReactionsLeukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia, aplastic anemia, and pancytopenia have been reported with sulfonylureas.
Metabolic ReactionsHepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas; however, hepatic porphyria has not been reported with glyburide and disulfiram-like reactions have been reported very rarely.Cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.
Other ReactionsChanges in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. These are thought to be related to fluctuation in glucose levels.In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.
Dosage And Administration
Patients should be retitrated when transferred from non-micronized glyburide tablets or other oral hypoglycemic agents.There is no fixed dosage regimen for the management of diabetes mellitus with glyburide tablets (micronized) or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored 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. Glycosylated hemoglobin levels may also be of value in monitoring the patient's response to therapy.Short-term administration of glyburide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.