Glyburide 1.25mg Information
Glyburide 1.25mg (Glyburide) Description
Micronized glyburide tablets contain micronized (smaller particle size) glyburide, which is an oral blood-glucose-lowering drug of the sulfonylurea class. Glyburide is a white, crystalline compound, formulated as micronized glyburide tablets of 1.5, 3 and 6 mg strengths for oral administration. Inactive ingredients: colloidal silicon dioxide, corn starch, lactose, magnesium stearate. In addition, the strength contains FD&C Blue No. 1 Aluminum Lake, and the tablet contains D&C Yellow No. 10 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 493.99. The structural formula is represented below:
Glyburide 1.25mg (Glyburide) Clinical Pharmacology
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 complementary mechanisms.
Some patients who are initially responsive to oral hypoglycemic drugs, including glyburide, may become unresponsive or poorly responsive over time. Alternatively, glyburide 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, 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.
Single dose studies with micronized glyburide tablets 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 glyburide tablets 5 mg. Therefore, the patient should be retitrated.
In a single-dose bioavailability study (see Figure A) in which subjects received micronized glyburide tablets 3 mg and glyburide tablets 5 mg with breakfast, the peak of the mean serum glyburide concentration-time curve was 97.2 ng/mL for micronized glyburide tablets 3 mg and 87.5 ng/mL for glyburide tablets 5 mg. The mean of the individual maximum serum concentration values of glyburide (C) from micronized glyburide tablets 3 mg was 106 ng/mL and that from glyburide tablets 5 mg 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 glyburide tablets 5 mg.
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 buildup of drug in tissue depots.
In a steady-state study in diabetic patients receiving micronized glyburide tablets 6 mg once daily or micronized glyburide tablets 3 mg twice daily, no difference was seen between the two dosage regimens in average 24-hour glyburide concentrations following two weeks of dosing. The once-daily and twice-daily regimens provided equivalent glucose control as measured by fasting plasma glucose levels, 4-hour postprandial glucose AUC values, and 24-hour glucose AUC values. Insulin AUC response over the 24-hour period was not different for the two regimens. There were differences in insulin response between the regimens for the breakfast and supper 4-hour postprandial periods, but these did not translate into differences in glucose control.
The serum concentration of glyburide in normal subjects decreased with a half-life of about four hours.
In single dose studies in fasting normal subjects who were administered glyburide (MICRONASE Tablets) in doses ranging from 1.25 mg to 5 mg, the degree and duration of blood glucose lowering is proportional to the dose administered and to the area under the drug level concentration-time curve. The blood glucose lowering effect persists for 24 hours following single morning doses in nonfasting diabetic patients. Under conditions of repeated administration in diabetic patients, however, there is no reliable correlation between blood drug levels and fasting blood glucose levels. A one year study of diabetic patients treated with glyburide showed no reliable correlation between administered dose and serum drug level.
The major metabolite of glyburide is the 4-trans-hydroxy derivative. A second metabolite, the 3-cis-hydroxy derivative, also occurs. These metabolites probably contribute no significant hypoglycemic action in humans since they are only weakly active (1/400th and 1/40th as active, respectively, as glyburide) in rabbits.
Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.
Sulfonylurea drugs are extensively bound to serum proteins. Displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. , the protein binding exhibited by glyburide is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. Acidic drugs such as phenylbutazone, warfarin, and salicylates displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding glyburide. It has not been shown that this difference in protein binding will result in fewer drug-drug interactions with glyburide in clinical use.
Glyburide 1.25mg (Glyburide) Indications And Usage
Micronized glyburide tablets 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 insert).
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 micronized 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 micronized glyburide.
During maintenance programs, micronized glyburide should be discontinued if satisfactory lowering of blood glucose is no longer achieved. Judgment should be based on regular clinical and laboratory evaluations.
In considering the use of micronized glyburide in asymptomatic patients, it should be recognized that controlling blood glucose in non-insulin-dependent diabetes has not been definitely established to be effective in preventing the long-term cardiovascular or neural complications of diabetes.
Glyburide 1.25mg (Glyburide) Contraindications
Micronized glyburide tablets are contraindicated in patients with:
Glyburide 1.25mg (Glyburide) Precautions
Bioavailability studies have demonstrated that micronized glyburide tablets 3 mg provide serum glyburide concentrations that are not bioequivalent to those from glyburide tablets 5 mg. Therefore, patients should be retitrated when transferred from glyburide or other oral hypoglycemic agents.
Patients should be informed of the potential risks and advantages of micronized glyburide and of alternative modes of therapy. They also should be informed about the importance of adherence to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure also should be explained.
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 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.
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, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving glyburide, the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving glyburide, the patient should be observed closely for hypoglycemia.
A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism of action for this interaction is not known.
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.
Studies in rats at doses up to 300 mg/kg/day for 18 months showed no carcinogenic effects. Glyburide is nonmutagenic when studied in the Salmonella microsome test (Ames test) and in the DNA damage/alkaline elution assay.
No drug-related effects were noted in any of the criteria evaluated in the two-year oncogenicity study of glyburide in mice.
Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see ). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see ).
Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function.
Glyburide 1.25mg (Glyburide) Adverse Reactions
Liver function abnormalities, including isolated transaminase elevations, have been reported.
Gastrointestinal disturbances, , 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.
Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.
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.
In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.
Glyburide 1.25mg (Glyburide) Overdosage
Overdosage of sulfonylureas, including glyburide, can produce hypoglycemia. Mild hypoglycemic symptoms, without loss of consciousness or neurological findings, should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate which will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours, since hypoglycemia may recur after apparent clinical recovery.
Glyburide 1.25mg (Glyburide) Dosage And Administration
There is no fixed dosage regimen for the management of diabetes mellitus with micronized glyburide tablets 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, , inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, , 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 micronized glyburide may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
Glyburide 1.25mg (Glyburide) How Supplied
Micronized glyburide tablets are supplied as follows:
Store at controlled room temperature 20° to 25°C (68° to 77°F) [see USP]. Dispensed in well closed containers with safety closures. Keep container tightly closed.
Glyburide 1.25mg (Glyburide)
