DIAMICRON 80MG TAB (TABLET)

Dosage / Direction for Use: Adult <65 yr Initially 1 tab/day. Adjust dose depending on the blood glucose response & in steps of 1 tab at a time (at least 14 days should separate successive steps in the dose). Maintenance: 1-4 tab/day. Usual dose: 2 tab/day. >65 yr Initially ½ tab once daily, increase accordingly while keeping to steps of at least 14 days between successive levels & w/ close monitoring of blood glucose. Overdosage: An overdose of sulfonylurea drugs 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: Should be taken with food: Take w/ meals to minimize GI disturbances. 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. Lactation. Hypoglycemia. Malnutrition, irregular mealtimes, skipping meals, periods of fasting or dietary changes; imbalance between physical exercise & carbohydrate intake. Thyroid disorders, hypopituitarism & adrenal insufficiency. St. John's wort prep, fever, injury, infection or surgery may affect blood glucose control. Dysglycemia (concomitant use w/ fluoroquinolones, especially in elderly). Monitor blood glucose regularly. G6PD-deficiency. Contains lactose. Galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. May impair ability to drive or operate machinery. Avoid use during pregnancy. Elderly. 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 not known whether gliclazide or its metabolites are excreted in breast milk. Given the risk of neonatal hypoglycemia, the product is contraindicated in breastfeeding mother. A risk to the newborns/infants cannot be excluded. Fertility: No effect on fertility or reproductive performance was noted in male and female rats. 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) & tetracosactide; due to β2-agonist effects w/ ritodrine, salbutamol, terbutaline (IV route). Decreased exposure w/ St. John's wort (Hypericum perforatum). Dysglycemia w/ fluoroquinolones. Potentiation of anticoagulant therapy (warfarin). Mechanism of Action: Pharmacology: Pharmacodynamics: Gliclazide reduces blood glucose by stimulating insulin secretion from the βcells in the islets of Langerhans. 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. Hemo-vascular 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: Gliclazide is rapidly absorbed from the gastrointestinal tract, and the concentration in the blood reaches a maximum 11-14 hours after administration. In humans, binding to proteins is 94.2%. As the apparent terminal elimination half-life for gliclazide is 20 hours in humans, the drug can be administered in two daily doses. Elimination is mainly in the urine: less than 1% of the dose ingested is found unchanged in the urine.