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

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with GLUCOVANCE or any other antidiabetic drug.

Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (>5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally >5 mcg/mL.

Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g. acute congestive heart failure), excessive alcohol intake, and hepatic impairment.

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.

GLUCOVANCE is capable of producing hypoglycemia or hypoglycemic symptoms, therefore, proper patient selection, dosing, and instructions are important to avoid potential hypoglycemic episodes.

Renal or hepatic insufficiency may cause elevated drug levels of both glyburide and metformin hydrochloride, and the hepatic insufficiency may also diminish gluconeogenic capacity, both of which increase the risk of hypoglycemic reactions. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects.

Treatment of patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. In postmarketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.

In controlled clinical trials with metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum vitamin B12, without clinical manifestations, was observed in approximately 7% of patients.

Weight gain was seen with the addition of rosiglitazone to GLUCOVANCE, similar to that reported for thiazolidinedione therapy alone.

Cholestatic, hepatocellular, and mixed hepatocellular liver injury have been reported with postmarketing use of metformin.

Initiation of GLUCOVANCE in patients with an eGFR between 30 to 45 mL/minute/1.73 m² is not recommended. In patients taking GLUCOVANCE whose eGFR later falls below 45 mL/min/1.73 m² assess the benefit risk of continuing therapy. Discontinue GLUCOVANCE if the patient’s eGFR later falls below 30 mL/minute/1.73 m².

GLUCOVANCE is contraindicated in patients with:

• Severe renal impairment (eGFR below 30 mL/min/1.73m²) 
• 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

Discontinue GLUCOVANCE at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m²; in patients with a history of liver disease, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart GLUCOVANCE if renal function is stable.

Alcohol is known to potentiate the effect of metformin on lactate metabolism. Intervention: Warn patients against excessive alcohol intake while receiving GLUCOVANCE.

Patients receiving GLUCOVANCE in combination with a thiazolidinedione may be at risk for hypoglycemia.

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.

Certain drugs (e.g., nonsteroidal anti-inflammatory agents and other highly protein-bound drugs, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, beta-adrenergic blocking agents; potentially with ciprofloxacin, miconazole) may potentiate the hypoglycemic action of sulfonylureas, one of the components of GLUCOVANCE.

Carbonic anhydrase inhibitors (e.g.,topiramate, zonisamide, acetazolamide and dichlorphenamide) frequently cause a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with GLUCOVANCE may increase the risk for lactic acidosis.

An increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. Therefore concomitant administration of GLUCOVANCE and bosentan is contraindicated.

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 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.

Concomitant administration of colesevelam and glyburide resulted in reductions in glyburide AUC and Cmax of 32% and 47%, respectively.

Furosemide increased the metformin plasma and blood Cmax by 22% and blood AUC by 15%, without any significant change in metformin renal clearance.

Nifedipine appears to enhance the absorption of metformin.

Concomitant use of drugs that interfere with common renal tubular transport systems involved in the renal elimination of metformin (e.g., organic cationic transport-2 [OCT2] / multidrug and toxin extrusion [MATE] inhibitors such as ranolazine, vandetanib, dolutegravir, and cimetidine) could increase systemic exposure to metformin and may increase the accumulation of metformin and the risk for lactic acidosis.

Topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) frequently causes a decrease in serum bicarbonate and induce non-anion gap, hyperchloremic metabolic acidosis. Concomitant use of these drugs with GLUCOVANCE may increase the risk for lactic acidosis.

There are no adequate and well-controlled studies in pregnant women with GLUCOVANCE or its individual components. No animal studies have been conducted with the combined products in GLUCOVANCE.

Discuss the potential for unintended pregnancy with premenopausal women as therapy with GLUCOVANCE may result in ovulation in some anovulatory women.

Prolonged severe hypoglycemia (4-10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. It is not recommended that GLUCOVANCE be used during pregnancy. However, if it is used, GLUCOVANCE should be discontinued at least 2 weeks before the expected delivery date.

Published clinical lactation studies report that metformin is present in human milk which resulted in infant doses approximately 0.11% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.13 and 1. Breastfed infants of lactating women using GLUCOVANCE should be monitored for symptoms of hypoglycemia.

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• Polycystic ovary syndrome. GoToSource

• Metabolic syndrome. GoToSource

• Use in patients under the age of 18. GoToSource

Upper respiratory infection, musculoskeletal pain and hypoglycemia (low blood sugar). GoToSource

Lactic acidosis (too much acid in the body). GoToSource

Weight gain. GoToSource  

Hemolytic anemia (red blood cells are destroyed faster than they can be made). GoToSource

Vitamin B12 deficiency. GoToSurce

Increased cardiovascular risk. GoToSource

Lawsuits filed for heart attacks.