GLUVANS 1– Film Coated Tablets: Each Film Coated tablet contains: Metformin HCl 250 mg and Glyburide 1.25 mg.

GLUVANS 2– Film Coated Tablets: Each Film Coated tablet contains: Metformin HCl 500 mg and Glyburide 2.5 mg.

GLUVANS 3– Film Coated Tablets: Each Film Coated tablet contains: Metformin HCl 500 mg and Glyburide 5 mg.

Microcrystalline cellulose(Avicel PH-102),Croscarmellose sodium, Sodium starch glycolate, Sodium Lauryl Sulphate, Magnesium Stearate, Povidone K30, Aerosil 200, Ethanol, Hypromellose 606, Titanium Dioxide, Triacetine, Sunset  yellow, Quinolone yellow.

Pharmacological Classification: Antidiabetic Agents.

 

Glyburide and Metformin Hydrochloride Tablets combines 2 antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes.

Glyburide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets.

Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.

 

significant absorption of glyburide within 1 hour, peak drug levels at about 4 hours.

The absolute bioavailability of a 500 mg metformin hydrochloride tablet given under fasting conditions is approximately 50% to 60%. Food decreases the extent of and slightly delays the absorption of metformin.

Glyburide is extensively bound to serum proteins.

Metformin is negligibly bound to plasma proteins. Metformin partitions into erythrocytes.

the terminal half-life of Glyburide is about 10 hours. Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route.

Metformin hydrochloride: approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.

 

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

 

in patients with:

- Renal disease or renal dysfunction, which may also result from conditions such ascardiovascular collapse (shock), acute myocardial infarction, and septicemia.

- Known hypersensitivity to metformin hydrochloride or glyburide.

- Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin.

- Concomitant administration of bosentan.

Glyburide and Metformin Hydrochloride  Tablets should be temporarily discontinued in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials, because use of such products may result in acute alteration of renal function.

 

Most Common: Upper respiratory infection, Headache, Gastrointestinal Reactions (Diarrhea, Nausea/vomiting, Abdominal pain), Dizziness.

Hypoglycemia: The symptoms of hypoglycemia are: dizziness, shakiness, sweating, and Hunger.

 

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with Glyburide and Metformin Hydrochloride  Tablets; when it occurs, it is fatal in approximately 50%of cases. Lactic acidosis may also occur in association with anumber of pathophysiologic conditions, including diabetes mellitus, and whenever there is significanttissue hypoperfusion and hypoxemia.

The risk of lactic acidosis increases with the degree of renal dysfunction and the patient's age.

Glyburide and Metformin Hydrochloride  Tablets treatment should not beinitiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis.

 

Hypoglycemia: Glyburide and Metformin Hydrochloride Tablets is capable of producing hypoglycemia or hypoglycemic symptoms. Renal or hepatic insufficiency may cause elevated drug levels of both Glyburide and Metformin hydrochloride. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects.

Hemolytic anemia: Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents (glyburide) can lead to hemolytic anemia.

Monitoring of renal function: Before initiation of Glyburide and Metformin Hydrochloride Tablets therapy and at least annually thereafter, renal function should be assessed and verified as normal. In patients in whom development of renal dysfunction is anticipated, renal function should be assessed more frequently and Glyburide and Metformin Hydrochloride  Tablets discontinued if evidence of renal impairment is present.

Hypoxic states: Cardiovascular collapse (shock) from whatever cause, acute congestive heart failure, acute myocardial infarction, and other conditions characterized by hypoxemia have been associated with lactic acidosis and may also cause prerenal azotemia. When such events occur in patients on Glyburide and Metformin Hydrochloride  Tablets therapy, the drug should be promptly discontinued.

Surgical procedures: Glyburide and Metformin Hydrochloride  Tablets therapy should be temporarily suspended for any surgical procedure.

Alcohol intake: Patients should be warned against excessive alcohol intake, acute or chronic, while receiving Glyburide and Metformin Hydrochloride Tablets.

Impaired hepatic function: Glyburide and Metformin Hydrochloride Tablets should generally be avoided in patients with clinical or laboratory evidence of hepatic disease.

Vitamin B levels: a decrease to subnormal levels of previously normal serum vitamin B , without clinical manifestations, was observed in approximately 7% of patients. Such decrease, possibly due to interference with B absorption. Certain individuals (those with inadequate vitamin B or calcium intake or absorption) appear to be predisposed to developing subnormal vitamin B levels. In these patients, routine serum vitamin B measurements at 2- to 3-year intervals may be useful.

Addition of Thiazolidinediones to Glyburide and Metformin Hydrochloride Tablets Therapy: Patients receiving Glyburide and Metformin Hydrochloride Tablets in combination with a thiazolidinedione may be at risk for hypoglycemia, Weight gain, Hepatic effects.

 

Patients should be informed of the potential risks and benefits of Glyburide and Metformin Hydrochloride Tablets and alternative modes of therapy. They should also be informed about the importance of adherence to dietary instructions; a regular exercise program; and regular testing of blood glucose, glycosylated hemoglobin, renal function, and hematologic parameters.

The risks of lactic acidosis associated with metformin therapy, its symptoms, and conditions that predispose to its development, should be explained to patients. Patients should be advised to discontinue Glyburide and Metformin Hydrochloride Tablets immediately and promptly notify their health practitioner if unexplained hyperventilation, myalgia, malaise, unusual somnolence, or other nonspecific symptoms occur. Once a patient is stabilized on any dose level of Glyburide and Metformin Hydrochloride Tablets, gastrointestinal symptoms, which are common during initiation of metformin therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.

The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members.

Patients should be counseled against excessive alcohol intake, either acute or chronic, while receiving Glyburide and Metformin Hydrochloride Tablets.

 

Periodic fasting blood glucose (FBG) and HbA measurements should be performed to monitor therapeutic response.

 

Certain drugs tend to produce hyperglycemia and may lead to loss of blood glucose control. These drugs include thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid.

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).

concomitant administration of Glyburide and Metformin Hydrochloride Tablets and

bosentan is contraindicated.

A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported.

A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported.

Concomitant administration of colesevelam and glyburide resulted in reductions in glyburide AUC and Cmax Therefore, Glyburide and Metformin Hydrochloride Tablets should be administered at

least 4 hours prior to colesevelam.

Furosemide increased the metformin plasma and blood Cmax.

Nifedipine appears to enhance the absorption of metformin. Metformin had minimal effects on nifedipine.

Cationic drugs (eg, amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) that are eliminated by renal tubular secretion theoretically have the potential for interaction with metformin by competing for common renal tubular transport systems. Such interaction between metformin and oral cimetidine has been observed.

 

Category B

Glyburide and Metformin Hydrochloride Tablets should not be used during pregnancy unless clearly needed.

There are no adequate and well-controlled studies in pregnant women with Glyburide and Metformin Hydrochloride Tablets or its individual components.

It is not recommended that Glyburide and Metformin Hydrochloride Tablets be used during pregnancy. However, if it is used, Glyburide and Metformin Hydrochloride Tablets should be discontinued at least 2 weeks before the expected delivery date.

 

Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue Glyburide and Metformin Hydrochloride Tablets, taking into account the importance of the drug to the mother. If Glyburide and Metformin Hydrochloride Tablets is discontinued, and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

 

Because aging is associated with reduced renal function, Glyburide and Metformin Hydrochloride Tablets should be used with caution as age increases. Generally, elderly patients should not be titrated to the maximum dose of Glyburide and Metformin Hydrochloride Tablets.

 

Dosage of Glyburide and Metformin Hydrochloride Tablets must be individualized on the basis of both effectiveness and tolerance while not exceeding the maximum recommended daily dose of 20 mg glyburide/2000 mg metformin. Glyburide and Metformin Hydrochloride Tablets should be given with mealsand should be initiated at a low dose.

Recommended starting dose: 1.25 mg/250 mg once or twice daily with meals.

Dosage increases should be made in increments of 1.25 mg/250 mg per day every 2 weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. Glyburide and Metformin Hydrochloride Tablets 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia.

Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals.

For patients previously treated with combination therapy of glyburide (or another sulfonylurea) plus metformin, if switched to Glyburide and Metformin Hydrochloride Tablets, the starting dose should not exceed the daily dose of glyburide (or equivalent dose of another sulfonylurea) and metformin already being taken.

For patients not adequately controlled on Glyburide and Metformin Hydrochloride Tablets, a thiazolidinedione can be added to Glyburide and Metformin Hydrochloride Tablets therapy. When a thiazolidinedione is added to Glyburide and Metformin Hydrochloride Tablets therapy, the current dose of Glyburide and Metformin Hydrochloride Tablets can be continued and the thiazolidinedione initiated at its recommended starting dose.

 

Overdosage of sulfonylureas, including glyburide tablets, 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.

Overdose of metformin hydrochloride has occurred, including ingestion of amounts >50 g. Hypoglycemia was reported in approximately 10% of cases. Lactic acidosis has been reported in approximately 32% of metformin overdose cases.

Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.

 

- GLUVANS 1– Film Coated Tablets: A pack of 30 film coated tablets in blister.

- GLUVANS 2– Film Coated Tablets: A pack of 30 film coated tablets in blister.

- GLUVANS 3– Film Coated Tablets: A pack of 30 film coated tablets in blister.

 

Store GLUVANS –Film Coated Tablet at temperature below (25)°C. protect from light.