Glimepiride 2 mg Metformin 500 mg (SR) Tablet

Loss of control of blood glucose :

When a patient stabilized on any diabetic regimen, is exposed to stress such as fever, trauma, infection, or surgery, a temporary loss of glycemic control may occur. At such times, it may be necessary to withhold the diabetic regime and temporarily administer insulin. The oral antidiabetic therapy may be reinstituted after the acute episode is resolved.

Alcohol intake :

Alcohol is known to potentiate the effect of metformin on lactate metabolism.Patients should be warned against excessive alcohol intake, while receiving metformin.

Pregnancy :

Abnormal blood glucose levels during pregnancy are associated with the higher incidence of congenital abnormalities. Most experts suggest insulin be used to maintain the blood glucose levels as close to normal as possible. The use of glimepiride and metformin combination is not recommended for use in pregnancy.

Lactation :

Studies in lactating rats show that metformin is excreted into milk and reaches levels comparable to those in plasma. Similar studies have not been conducted on nursing mothers. Also Glimepiride should not be used by breast-feeding mothers. Hence, the use of glimepiride and metformin combination is not recommended for use in lactating mothers, and if the diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

Cardiac effects :

The administration of oral hypoglycemic drugs (tolbutamide) has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. In view of close similarities between the oral hypoglycemic drugs, this warning also applies for glimepiride.

Lactic acidosis :

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with glimepiride and metformin combination therapy; when it occurs, it is fatal in approximately 50% of cases.When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 μg/mL are generally found. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient
years). Reported cases have occurred primarily in diabetic patients with significant renal insufficiency and congestive heart failure. Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis, metformin should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable, prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin.

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 metformin therapy, the drug should be promptly discontinued.

Hemolytic anemia :

Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia. Since glimepiride is a sulfonylurea agent, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered.

Overdosage of sulfonylureas, including glimepiride, can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic 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 IV injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours, because hypoglycemia may recur after apparent clinical recovery. Lactic acidosis is a rare, but serious, metabolic complication that can occur if metformin accumulates during treatment due to overdosing. Strict monitoring should be continued until the doctor is sure that the patient is out of danger.