Cardiac Effects: 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. In view of close similarities between the oral hypoglycemic drugs, this warning also applies for Gliclazide.
Lactic acidosis: Lactic acidosis is a rare, but serious, metabolic complication that can occur due to Metformin accumulation during treatment with Gliclazide and Metformin combination therapy; when it occurs, it is fatal approximately 50% of cases. When Metformin is implicated as the cause of lactic acidosis, Metformin plasma levels >5 ug/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.
Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia. Proper patient selection, dosage and instructions are important to avoid hypoglycemic episodes.
Loss of control of blood glucose: When a patient stabilized in 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.
Surgical procedures: Oral antidiabetic therapy should be temporarily suspended for any surgical procedure (except minor procedures not associated with restricted intake of food and fluids) and should not be restarted until the patient's oral intake has resumed and renal function has been evaluated as normal.
Alcohol intake: Alcohol is known to potentiate the effect of Metformin on lactate metabolism. Patients, therefore, should be warned against excessive alcohol intake, acute or chronic, while receiving Metformin.
Effects on ability to drive and use machine: There is no pattern of reported adverse events suggesting that patients taking Gliclazide and Metformin combination will have any impairment of ability to drive and use hazardous machinery.
Renal impairment: The use of Gliclazide and Metformin is contraindicated in patients with renal impairment.
Hepatic impairment: The use of Gliclazide and Metformin is not recommended in patients with hepatic impairment.
Use in Children: Safety and effectiveness of Gliclazide and Metformin combination in pediatric patients have not been established.
Use in Elderly: Metformin is known to be excreted by the kidneys and because the risk of serious adverse reactions to the drug is greater in patients with impaired renal function, hence Gliclazide and Metformin should be used only in patients with normal renal function.
Because aging is associated with reduced renal function the use of Gliclazide and Metformin combination should be with caution as age increases. Care should be taken with the dose selection and regular renal function be monitored.