Elsaad products
Member Login


New Products
Newsletter
 
 
Our Products
Product Name
:
GLUVANS
Chemical Name
:
Glyburide+Metformin HCl
Therapeutic Category
:
Anti-diabetic drugs
Pharmacologic Category
:
Antidiabetic Agent, Biguanide - Antidiabetic Agent, Sulfonylurea
Pharmaceutical Form
:
Tablets
Composition
:
Glyburide 2.5mg+Metformin HCl 500mg / Glyburide 5mg+Metformin HCl 500mg
Dosing
 
Dosing: Adult
Note: Dose must be individualized. All doses should be taken with a meal. Twice daily dosage should be taken with the morning and evening meals. Dosages expressed as glyburide/metformin components.
Type 2 diabetes: Oral:
No prior treatment with sulfonylurea or metformin: Initial: 1.25 mg/250 mg once daily with a meal; patients with Hb A1c >9% or fasting plasma glucose (FPG) >200 mg/dL may start with 1.25 mg/250 mg twice daily with meals. Adjustment: Dosage may be increased in increments of 1.25 mg/250 mg, at intervals of not less than 2 weeks; maximum daily dose: 10 mg/2000 mg (limited experience with higher doses); Note: Doses of 5 mg/500 mg should not be used as initial therapy, due to risk of hypoglycemia.
Previously treated with a sulfonylurea or metformin alone: Initial: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals; increase in increments no greater than 5 mg/500 mg; maximum daily dose: 20 mg/2000 mg
Note: When switching patients previously on a sulfonylurea and metformin together, do not exceed the daily dose of glyburide (or glyburide equivalent) or metformin. When adding thiazolidinedione, continue glyburide and metformin at current dose and initiate thiazolidinedione at recommended starting dose.
Combination with thiazolidinedione: May be combined with a thiazolidinedione in patients with an inadequate response to glyburide/metformin therapy, however the risk of hypoglycemia may be increased.

Dosing: Geriatric

Refer to adult dosing. Adjust carefully to renal function. Should not be used in patients ≥80 years of age unless renal function is verified as normal. Do not titrate to maximum dose.
Use
 
Adjunct to diet and exercise for the management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)
Adverse Reactions
 
Metformin :
>10%:
Gastrointestinal: Diarrhea (10% to 53%), nausea/vomiting (7% to 26%), flatulence (12%)
Neuromuscular & skeletal: Weakness (9%)
1% to 10%:
Cardiovascular: Chest discomfort, flushing, palpitation
Central nervous system: Headache (6%), chills, dizziness, lightheadedness
Dermatologic: Rash
Endocrine & metabolic: Hypoglycemia
Gastrointestinal: Indigestion (7%), abdominal discomfort (6%), abdominal distention, abnormal stools, constipation, dyspepsia/ heartburn, taste disorder
Neuromuscular & skeletal: Myalgia
Respiratory: Dyspnea, upper respiratory tract infection
Miscellaneous: Decreased vitamin B12 levels (7%), increased diaphoresis, flu-like syndrome, nail disorder
<1% (Limited to important or life-threatening): Lactic acidosis, leukocytoclastic vasculitis, megaloblastic anemia, pneumonitis

Glyburide :
Cardiovascular: Vasculitis
Central nervous system: Dizziness, headache
Dermatologic: Angioedema, erythema, maculopapular eruptions, morbilliform eruptions, photosensitivity reaction, pruritus, purpura, rash, urticaria
Endocrine & metabolic: Disulfiram-like reaction, hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)
Gastrointestinal: Anorexia, constipation, diarrhea, epigastric fullness, heartburn, nausea
Genitourinary: Nocturia
Hematologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, pancytopenia, porphyria cutanea tarda, thrombocytopenia
Hepatic: Cholestatic jaundice, hepatitis, liver failure, transaminase increased
Neuromuscular & skeletal: Arthralgia, myalgia, paresthesia
Ocular: Blurred vision
Renal: Diuretic effect (minor)
Miscellaneous: Allergic reaction
Contraindications
 
Hypersensitivity to glyburide, metformin, or any component of the formulation; renal disease or renal dysfunction (serum creatinine ≥1.5 mg/dL in males or ≥1.4 mg/dL in females, or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse, acute myocardial infarction, and septicemia; acute or chronic metabolic acidosis with or without coma (including diabetic ketoacidosis)
Note: Temporarily discontinue in patients undergoing radiologic studies in which intravascular iodinated contrast materials are utilized. Temporarily discontinue for surgical procedures.
Warnings / Precautions Drug
 
Boxed warnings:
• Lactic acidosis: See “Concerns related to adverse effects” below.
Concerns related to adverse effects:
• Cardiovascular mortality: Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association. Metformin does not appear to share this risk.
• Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly patients, malnourished patients and in patients with impaired renal, hepatic, adrenal and/or pituitary function; use with caution.
• Lactic acidosis: [U.S. Boxed Warning]: Lactic acidosis is a rare, but potentially fatal and severe consequence of therapy with metformin. Lactic acidosis should be suspected in any patient with diabetes receiving metformin with evidence of acidosis but without evidence of ketoacidosis. Discontinue metformin in clinical situations predisposing to hypoxemia, including conditions such as cardiovascular collapse, respiratory failure, acute myocardial infarction, acute congestive heart failure, and septicemia. The risk of accumulation and lactic acidosis increases with the degree of impairment of renal function.
• Sulfonamide allergy: Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is not specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.
Disease-related concerns:
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency: Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.
• Heart failure: Use metformin with caution in patients with heart failure requiring pharmacologic management, particularly in patients with unstable or acutely decompensated heart failure; risk of lactic acidosis may be increased secondary to hypoperfusion.
• Hepatic impairment: Avoid metformin use in patients with impaired liver function due to potential for lactic acidosis.
• Renal impairment: Metformin is substantially excreted by the kidney; patients with renal function below the limit of normal for their age should not receive therapy. Use of concomitant medications that may affect renal function (ie, affect tubular secretion) may also affect metformin disposition. Metformin should be withheld in patients with dehydration and/or prerenal azotemia.
• Stress-related states: It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery).
Concurrent drug therapy issues:
• Thiazolidinediones: Concurrent use with a thiazolidinedione may increase risk of hypoglycemia and/or weight gain. Liver function tests should be monitored periodically with concurrent use.
Special populations:
• Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. Metformin should not be initiated in patients ≥80 years of age unless normal renal function is confirmed.
Other warnings/precautions:
• Ethanol use: Instruct patients to avoid excessive acute or chronic ethanol use; ethanol may potentiate metformin's effect on lactate metabolism.
• Iodinated contrast: Metformin therapy should be temporarily discontinued prior to or at the time of intravascular administration of iodinated contrast media (potential for acute alteration in renal function). Metformin should be withheld for 48 hours after the radiologic study and restarted only after renal function has been confirmed as normal.
• Secondary failure: Loss of efficacy may be observed following prolonged use as a result of the progression of type 2 diabetes mellitus which results in continued beta cell destruction. In patients who were previously responding to sulfonylurea therapy, consider additional factors which may be contributing to decreased efficacy (eg, inappropriate dose, nonadherence to diet and exercise regimen). If no contributing factors can be identified, consider discontinuing use of the sulfonylurea due to secondary failure of treatment. Additional antidiabetic therapy (eg, insulin) will be required.
• Surgical procedures: Metformin therapy should be suspended for any surgical procedures requiring food or fluid restriction (resume only after normal intake resumed and normal renal function is verified).
Interactions
 
Alcohol (Ethyl): Sulfonylureas may enhance the adverse/toxic effect of Alcohol (Ethyl). A flushing reaction may occur. Risk C: Monitor therapy
Beta-Blockers: May enhance the hypoglycemic effect of Sulfonylureas. Cardioselective beta-blockers (eg, acebutolol, atenolol, metoprolol, and penbutolol) may be safer than nonselective beta-blockers. All beta-blockers appear to mask tachycardia as an initial symptom of hypoglycemia. Ophthalmic beta-blockers are probably associated with lower risk than systemic agents. Exceptions: Levobunolol; Metipranolol. Risk C: Monitor therapy
Bosentan: GlyBURIDE may enhance the hepatotoxic effect of Bosentan. GlyBURIDE may increase the metabolism of Bosentan. Bosentan may increase the metabolism of GlyBURIDE. Risk X: Avoid combination
Cephalexin: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Chloramphenicol: May decrease the metabolism of Sulfonylureas. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of MetFORMIN. Risk D: Consider therapy modification
Cimetidine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Clarithromycin: May increase the serum concentration of GlyBURIDE. Risk C: Monitor therapy
Colesevelam: May decrease the serum concentration of GlyBURIDE. Risk D: Consider therapy modification
Corticosteroids (Orally Inhaled): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Corticosteroids (Systemic): May diminish the hypoglycemic effect of Antidiabetic Agents. In some instances, corticosteroid-mediated HPA axis suppression has led to episodes of acute adrenal crisis, which may manifest as enhanced hypoglycemia, particularly in the setting of insulin or other antidiabetic agent use. Risk C: Monitor therapy
Cyclic Antidepressants: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
CycloSPORINE: May diminish the therapeutic effect of GlyBURIDE. GlyBURIDE may increase the serum concentration of CycloSPORINE. Risk C: Monitor therapy
CycloSPORINE (Systemic): May diminish the therapeutic effect of GlyBURIDE. GlyBURIDE may increase the serum concentration of CycloSPORINE (Systemic). Risk C: Monitor therapy
CYP2C9 Inducers (Highly Effective): May increase the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Moderate): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
CYP2C9 Inhibitors (Strong): May decrease the metabolism of CYP2C9 Substrates (High risk). Risk D: Consider therapy modification
Dofetilide: MetFORMIN may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
Fibric Acid Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Risk C: Monitor therapy
Fluconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
GLP-1 Agonists: May enhance the hypoglycemic effect of Sulfonylureas. Management: Consider sulfonylurea dose reductions when used in combination with GLP-1 agonists. Risk D: Consider therapy modification
Glycopyrrolate: May increase the serum concentration of MetFORMIN. Risk C: Monitor therapy
Herbs (Hypoglycemic Properties): May enhance the hypoglycemic effect of Hypoglycemic Agents. Risk C: Monitor therapy
Hypoglycemic Agents: May enhance the adverse/toxic effect of other Hypoglycemic Agents. Risk C: Monitor therapy
Iodinated Contrast Agents: May enhance the adverse/toxic effect of MetFORMIN. Renal dysfunction that may be caused by iodinated contrast agents may lead to metformin-associated lactic acidosis. Management: Withhold metformin from all patients receiving intravascular iodinated contrast agents prior to or at the time of the procedure and for at least 48 hrs thereafter. Document adequate renal function before restarting metformin. Risk D: Consider therapy modification
Luteinizing Hormone-Releasing Hormone Analogs: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Peginterferon Alfa-2b: May decrease the serum concentration of CYP2C9 Substrates (High risk). Risk C: Monitor therapy
Pegvisomant: May enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Quinolone Antibiotics: May enhance the hypoglycemic effect of Sulfonylureas. This appears to be particularly concerning early in the course of combination therapy. Quinolone Antibiotics may diminish the hypoglycemic effect of Sulfonylureas. With longer-term combination, there is a greater risk of hyperglycemia. Risk C: Monitor therapy
Ranitidine: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Rifampin: May increase the metabolism of Sulfonylureas. Risk C: Monitor therapy
Salicylates: May enhance the hypoglycemic effect of Sulfonylureas. Of concern with regular, higher doses of salicylates, not sporadic, low doses. Risk C: Monitor therapy
Somatropin: May diminish the hypoglycemic effect of Antidiabetic Agents. Risk D: Consider therapy modification
Sulfonamide Derivatives: May enhance the hypoglycemic effect of Sulfonylureas. Exceptions: Sulfacetamide. Risk C: Monitor therapy
Thiazide Diuretics: May diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy
Voriconazole: May increase the serum concentration of Sulfonylureas. Risk C: Monitor therapy
Pregnancy
 
B
Pregnancy Implications
Animal reproduction studies were not conducted with this combination. Adverse events were not observed in animal studies of the individual agents; therefore, glyburide/metformin is classified as pregnancy category B. Refer to individual agents.
Lactation
 
Excretion in breast milk unknown/not recommended
Breast-Feeding Considerations
Refer to individual agents.
Monitoring Parameters
 
Signs and symptoms of hypoglycemia, urine for glucose and ketones, FPG, Hb A1c, and fructosamine. Initial and periodic monitoring of hematologic parameters (eg, hemoglobin/hematocrit and red blood cell indices) and renal function should be performed; monitor at least annually once patient is on maintenance therapy. While megaloblastic anemia has been rarely seen with metformin, if suspected, vitamin B12 deficiency should be excluded.
Reference Range
Recommendations for glycemic control in adults with diabetes:
Hb A1c: <7%
Preprandial capillary plasma glucose: 70-130 mg/dL
Peak postprandial capillary blood glucose: <180 mg/dL
Blood pressure: <130/80 mm Hg
Mechanism of Action
 
The combination of glyburide and metformin is used to improve glycemic control in patients with type 2 diabetes mellitus by using two different, but complementary, mechanisms of action:
Glyburide: Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites
Metformin: Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization)
Pharmacodynamics / Kinetics
 
Bioavailability: 18% with 2.5 mg glyburide/500 mg metformin dose; 7% with 5 mg glyburide/500 mg metformin dose; bioequivalence has not been established between GLUVANS® and single ingredient glyburide products; bioavailability was greater than that of a single ingredient brand of glyburide
Time to peak: 2.75 hours when taken with food
Glyburide:
Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose
Duration: ≤24 hours
Absorption: Significant within 1 hour
Distribution: 9-10 L
Protein binding, plasma: >99% primarily to albumin
Metabolism: Hepatic; forms metabolites (weakly active)
Bioavailability: Variable among oral dosage forms
Half-life elimination: Diabeta®: 10 hours; Glynase® PresTab®: ~4 hours; may be prolonged with renal or hepatic impairment
Time to peak, serum: Adults: 2-4 hours
Excretion: Feces (50%) and urine (50%) as metabolites

Metformin: This component is bioequivalent to metformin coadministration with glyburide.
 
   
 
Powered by: TSS-EST.COM