DIAMICRON MR 60MG TAB (TABLET)

Dosage / Direction for Use: Initially 30 mg daily (½ tab), may be increased to 60, 90 or 120 mg daily, in successive steps. Interval between each dose increment should be at least 1 mth except in patients whose blood glucose has not reduced after 2 wk of treatment. Dose may be increased at the end of the 2nd wk of treatment. Max: 120 mg daily. Switching from Gliclazide 80 mg tab to Gliclazide 60 mg MR tab: 1 tab Gliclazide (Diamicron) 80 mg tab is comparable to 30 mg MR formulation (eg, ½ tab of Diamicron MR 60 mg). Consequently, the switch can be performed w/ careful blood monitoring. Switching from another oral antidiabetic agent to Gliclazide 60 mg MR tab: Initially 30 mg/day, followed by a stepwise increase in dose, depending on the metabolic response. Patients at risk of hypoglycemia Initially min of 30 mg daily. Overdosage: An overdose of sulfonylurea may cause hypoglycemia. Moderate symptoms of hypoglycemia, without any loss of consciousness or neurological signs, must be corrected by carbohydrate intake, dose adjustment and/or change of diet. Strict monitoring should be continued until the doctor is sure that the patient is out of danger. Severe hypoglycemic reactions, with coma, convulsions or other neurological disorders are possible and must be treated as a medical emergency, requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid I.V. injection of 50 mL of concentrated glucose solution (20 to 30 %). This should be followed by continuous infusion of a more dilute glucose solution (10 %) at a rate that will maintain blood glucose levels above 1 g/L. Patients should be monitored closely and, depending on the patient's condition after this time, the doctor will decide if further monitoring is necessary. Dialysis is of no benefit to patients due to the strong binding of gliclazide to proteins. Administration: May be taken with or without food: Swallow whole & divided halves, do not chew/crush. Contraindications: Hypersensitivity to gliclazide, other sulfonylureas or sulfonamides. Type 1 diabetes; diabetic pre-coma & coma, diabetic ketoacidosis. Concomitant use w/ miconazole. Severe renal or hepatic insufficiency. Special Precautions: 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 sulfonylurea. 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 insufficiency; Severe hepatic insufficiency; Overdose of GLICLAZIDE (DIAMICRON); Certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency; Concomitant administration of certain other medicinal products. 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, 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 control: Blood glucose control in a patient receiving antidiabetic treatment may be affected by any of the following: St John's Wort (Hypericum perforatum) preparations, 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 (DIAMICRON MR) 60 mg 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. Excipients: GLICLAZIDE (DIAMICRON MR) 60 mg should not be administered to patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption. Driving and Using Machines: GLICLAZIDE (DIAMICRON MR) 60 mg has no or negligible influence on the ability to drive and use machines. However, patients should be made aware of the symptoms of hypoglycemia and should be careful if driving or operating machinery, especially at the beginning of treatment. Use In Pregnancy & Lactation: Pregnancy: There is no or limited amount of data (less than 300 pregnancy outcomes) from the use of gliclazide in pregnant women, even though there are few data with other sulfonylurea. In animal studies, gliclazide is not teratogenic. As a precautionary measure, it is preferable to avoid the use of Gliclazide during pregnancy. Control of diabetes should be obtained before the time of conception to reduce the risk of congenital abnormalities linked to uncontrolled diabetes. Oral hypoglycemic agents are not suitable, insulin is the drug of first choice for treatment of diabetes during pregnancy. It is recommended that oral hypoglycemic therapy is changed to insulin before a pregnancy is attempted, or as soon as pregnancy is discovered. Breastfeeding: It is unknown whether gliclazide or its metabolites are excreted in human milk. Given the risk of neonatal hypoglycemia, the product is therefore contraindicated in breastfeeding mother. A risk to the newborns/infants cannot be excluded. Special Precautions for Disposal: No special requirements. Any unused product or waste material should be disposed of in accordance with local requirements. Side Effects / Adverse Reactions: Hypoglycemia, sweating, clammy skin, anxiety, tachycardia, HTN, palpitations, angina pectoris & cardiac arrhythmia. Abdominal pain, nausea, vomiting, dyspepsia, diarrhea & constipation. Rash, pruritus, urticaria, angioedema, erythema, maculopapular rashes, bullous reactions (eg, Stevens-Johnson syndrome & toxic epidermal necrolysis), & exceptionally, drug rash w/ eosinophilia & systemic symptoms (DRESS); raised hepatic enzyme levels (AST, ALT, alkaline phosphatase), hepatitis; transient visual disturbances. Interactions: Increased hypoglycemia w/ miconazole (systemic route, oromucosal gel); phenylbutazone (systemic route); alcoholic drinks & any medicinal products containing alcohol (antabuse effect). Potentiate blood glucose lowering effect w/ other antidiabetic agents (insulin, acarbose, metformin, thiazolidinediones, dipeptidylpeptidase-4 inhibitors, GLP-1 receptor agonists), β-blockers, fluconazole, ACE inhibitors (captopril, enalapril), H2-receptor antagonists, MAOIs, sulfonamides, clarithromycin & NSAIDs. Diabetogenic effect of danazol. Increased blood glucose levels (reduced insulin release) w/ chlorpromazine (>100 mg/day); w/ possible ketosis (reduced carbohydrates tolerance) w/ glucocorticoids (systemic & local route, IA, cutaneous & rectal prep) & tetracosactrin. Increased blood glucose levels due to β-2 agonist effects w/ ritodrine, salbutamol, terbutaline (IV route). Decreased exposure w/ St. John's wort (H. perforatum). Dysglycemia w/ fluoroquinolones. Potentiation of anticoagulant therapy (warfarin). Mechanism of Action: Pharmacology: Pharmacodynamics: Mechanism of action: Gliclazide is a hypoglycemic sulfonylurea oral antidiabetic active substance differing from other related compounds by an N-containing heterocyclic ring with an endocyclic bond. Gliclazide reduces blood glucose levels by stimulating insulin secretion from the β-cells of the islets of Langerhans. Increase in postprandial insulin and C-peptide secretion persists after two years of treatment. In addition to these metabolic properties, gliclazide has hemovascular properties. Pharmacodynamic effects: Effects on insulin release: In type 2 diabetics, gliclazide restores the first peak of insulin secretion in response to glucose and increases the second phase of insulin secretion. A significant increase in insulin response is seen in response to stimulation induced by a meal or glucose. Hemovascular properties: Gliclazide decreases microthrombosis by two mechanisms which may be involved in complications of diabetes: A partial inhibition of platelet aggregation and adhesion, with a decrease in the markers of platelet activation (beta thromboglobulin, thromboxane B2). An action on the vascular endothelium fibrinolytic activity with an increase in tPA activity. Pharmacokinetics: Absorption: Plasma levels increase progressively during the first 6 hours, reaching a plateau which is maintained from the sixth to the twelfth hour after administration. Intra-individual variability is low. Gliclazide is completely absorbed. Food intake does not affect the rate or degree of absorption. Distribution: Plasma protein binding is approximately 95%. The volume of distribution is around 30 liters. A single daily intake of GLICLAZIDE (DIAMICRON MR) 60 mg maintains effective gliclazide plasma concentrations over 24 hours. Biotransformation: Gliclazide is mainly metabolized in the liver and excreted in the urine: less than 1% of the unchanged form is found in the urine. No active metabolites have been detected in plasma. Elimination: The elimination half-life of gliclazide varies between 12 and 20 hours. Linearity/non-linearity: The relationship between the dose administered ranging up to 120 mg and the area under the concentration time curve is linear. Special populations: Elderly: No clinically significant changes in pharmacokinetic parameters have been observed in elderly patients.