Glubitor/Glubitor-OD Special Precautions

Glubitor/Glubitor-OD (PR tab): Hypoglycemia: This treatment should be prescribed only if the patient is likely to have a regular food intake (including breakfast). It is important to have a regular carbohydrate intake due to the increased risk of hypoglycemia if a meal is taken late, if an inadequate amount of food is consumed or if the food is low in carbohydrate.
Hypoglycemia is more likely to occur during low-calorie diets, following prolonged or strenuous exercise, alcohol intake or if a combination of hypoglycemic agents is being used.
Hypoglycemia may occur following administration of sulfonylureas (see ADVERSE REACTIONS). Some cases may be severe and prolonged. Hospitalization may be necessary and glucose administration may need to be continued for several days.
Careful selection of patients, of the dose used, and clear patient directions are necessary to reduce the risk of hypoglycemic episodes.
Factors which increase the risk of hypoglycemia: Patient refuses or (particularly in elderly subjects) is unable to cooperate; Malnutrition, irregular mealtimes, skipping meals, periods of fasting or dietary changes; Imbalance between physical exercise and carbohydrate intake; Renal impairment/insufficiency; Severe hepatic impairment/insufficiency; Overdose of gliclazide/gliclazide prolonged-release tablet; Certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency; Concomitant administration of/with certain other medicines (see INTERACTIONS).
Renal and hepatic insufficiency: The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic insufficiency or severe renal failure. A hypoglycemic episode occurring in these patients may be prolonged, so appropriate management should be initiated.
Patient information: The risks of hypoglycemia, together with its symptoms (see ADVERSE REACTIONS), treatment, and conditions that predispose to its development, should be explained to the patient and to family members.
The patient should be informed of the importance of following dietary advice, of taking regular exercise, and of regular monitoring of blood glucose levels.
Poor blood glucose/sugar control(s): The blood glucose control in a patient receiving antidiabetic treatment may be affected by any of the following: St. John's Wort (Hypericum perforatum) preparations (see INTERACTIONS), fever, trauma, infection or surgical intervention. In some cases, it may be necessary to administer insulin.
The hypoglycemic efficacy of any oral antidiabetic agent, including gliclazide, is attenuated over time in many patients: this may be due to progression in the severity of the diabetes, or to a reduced response to treatment. This phenomenon is known as secondary failure which is distinct from primary failure, when an active substance is ineffective as first-line treatment. Adequate dose adjustment and dietary compliance should be considered before classifying the patient as secondary failure.
Dysglycemia: Disturbances in blood glucose, including hypoglycemia and hyperglycemia have been reported, in diabetic patients receiving concomitant treatment with fluoroquinolones, especially in elderly patients. Indeed, careful monitoring of blood glucose is recommended in all patients receiving at the same time gliclazide and a fluoroquinolone.
Laboratory tests: Measurement of glycated hemoglobin levels (or fasting venous plasma glucose) is recommended in assessing blood glucose control. Blood glucose self-monitoring may also be useful.
Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to hemolytic anemia. Since gliclazide belongs to the chemical class of sulfonylurea drugs, caution should be used in patients with G6PD-deficiency and a non-sulfonylurea alternative should be considered.
Effects on ability to drive and use machines: Gliclazide has no or negligible influence on the ability to drive and use machines. However, patients should be informed that their concentration may be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment.
Glubitor-OD (MR tab): Development of complications peculiar to diabetes mellitus (e.g., heart disease, blindness, kidney disease, hypertension, nerve damage, etc.) will not be prevented by the use of gliclazide.
Gliclazide should not be used as a substitute for diet. It must be considered only as an additional treatment to proper dietary regimen.
Administration of gliclazide over a long period of time decreases its efficacy in many patients. This may be due to continuing depletion of β-cell reserve. Discontinue the use of gliclazide if a loss of adequate blood glucose-lowering response is detected. Insulin therapy may be required in these patients.
Hypoglycemia: All sulfonylureas, including gliclazide, may cause severe hypoglycemia. Debilitated or malnourished patients, those with adrenal, pituitary, renal or hepatic insufficiency and patients controlled with diet alone are particularly susceptible to the hypoglycemic action of gliclazide. Use of gliclazide in combination with other oral hypoglycemic agents may increase the potential for hypoglycemia.
Inadequate caloric intake, severe or prolonged exercise, and alcohol ingestion may also increase the risk of hypoglycemia.
Gliclazide overdose, certain endocrine disorders (i.e., thyroid disorders, hypopituitarism and adrenal insufficiency) as well as withdrawal of prolonged and/or high dose corticosteroid therapy, severe vascular disease (severe coronary heart disease, severe carotid impairment, diffuse vascular disease) and concomitant administration of certain drugs (see INTERACTIONS) may also increase the risk of hypoglycemia.
The following measures are recommended to reduce the risk of hypoglycemia: initiate treatment of type 2 diabetes mellitus by diet alone, if possible; take into account the patient's age: blood sugar levels not strictly controlled by diet alone might be acceptable in the elderly; adjust gliclazide dose according to the blood glucose response and to the 24-hour urinary glucose during the first days of treatment.
Patients with mild symptoms of hypoglycemia such as sweating, pallor, hunger pangs, tachycardia, sensation of malaise may require treatment with oral glucose and adjustments in gliclazide dose and/or meal patterns.
Loss of Control of Blood Glucose: Exposure to stress such as fever, trauma, infection, or surgery may lead to loss of glycemic control. Temporary discontinuation of oral hypoglycemic therapy and administration of insulin may be necessary in such cases.
Progression of the severity of diabetes may lead to secondary failure or decreased effectiveness of any hypoglycemic drug (including gliclazide). Adequate assessment of dosage adjustment and diet adherence is necessary before classifying secondary failure in a patient. Insulin therapy should be initiated in patients who experience secondary failure after therapy with gliclazide.
Increased Risk of Cardiovascular Mortality: Based on a long term prospective study conducted by the University Group Diabetes Program (UGDP), it has been reported that diabetic patients treated for 5-8 years with diet plus a fixed dose of tolbutamide (1.5 g/day), a sulfonylurea, had a risk of cardiovascular mortality approximately 2 ½ times that of patients treated with diet alone.
In the United Kingdom Prospective Diabetes Study (UKPDS), however, intensive glycemic control with either sulfonylureas or insulin did not have an adverse effect on cardiovascular outcomes. Despite questions regarding the design of these studies and interpretation of the results, these studies provide a basis for caution especially in high risk patients with cardiovascular disease.
Hemolytic Anemia: Sulfonylureas may cause hemolytic anemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency. Use sulfonylureas with caution and consider a non-sulfonylurea alternative in these patients.
Transferring to Gliclazide: Patients who have been previously treated with sulfonylureas or biguanides alone or in combination may be transferred to gliclazide alone or in combination with other oral antidiabetics. Careful observation is essential during the transitional phase.
Generally, it is not recommended that insulin treated patients be transferred to gliclazide.
Renal and Hepatic Insufficiency: Treatment with gliclazide (i.e., initial dosing, dose increments, and maintenance dose) in patients with renal and hepatic insufficiency should start in small doses to avoid hypoglycemic reactions. Careful patient monitoring is also recommended since the metabolism and excretion of sulfonylureas such as gliclazide may be slowed in patients with impaired renal and hepatic function.
Effects on Ability to Drive or Use Machines: Patients who need to perform activities requiring mental alertness or physical coordination should avoid gliclazide since it may affect concentration if diabetes is not satisfactorily controlled (usually at the beginning of treatment).
Use in Children: The safety and efficacy of gliclazide in children have not been established. Gliclazide is not recommended for use in infants and children.
Use in the Elderly: Elderly patients are particularly susceptible to hypoglycemia. Moreover, hypoglycemia may be difficult to recognize in the elderly. Carefully determine the appropriate initial dose, dose increments and maintenance dose to avoid hypoglycemic episodes.
Glubitor-OD (PR tab): Other ingredients: Gliclazide prolonged-release tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Effects on ability to drive and use machines: Gliclazide 60 mg prolonged-release tablet has no or negligible influence on the ability to drive and use machines. However, patients must be made aware of the symptoms of hypoglycemia and should be careful if driving or operating machinery, especially at the beginning of treatment.