Full Prescribing Info
Each tablet contains gliclazide 80 mg.
Excipients/ Inactive Ingredients: colloidal silicon dioxide, croscarmellose sodium, lactose monohydrate, magnesium stearate, microcrystalline cellulose.
Pharmacology: Gliclazide is a hypoglycemic agent of the sulfonylurea group.
The hypoglycemic action of gliclazide is related to an improvement in insulin secretion from the functioning beta cells of the pancreas. It potentiates the insulin release and improves the dynamics of insulin.
Hemobiological properties of gliclazide have been observed in pharmacology studies. These are attributed to gliclazide action on the platelet behaviour, prostaglandin equilibrium and fibrinolysis.
Gliclazide is rapidly absorbed from the gastrointestinal tract and the plasma peak of gliclazide occurs between the 11th and 14th hour. In man it is highly bound to plasma proteins, about 94.2%. The mean elimination half-life in man approximates 10.4 hours.
Following oral administration the unchanged glidazide in plasma is extensively metabolized with little of the unchanged compound (<5%) appearing in the urine.
Gliclazide metabolites and conjugates are primarily eliminated via kidneys: 60 to 70%, and about 10 to 20% via feces.
Some five principal metabolites have been identified in urine, essentially oxidized and hydroxylated derivatives, some as glucuronic acid conjugates.
Control of hyperglycemia in gliclazide responsive diabetes mellitus of stable, mild, non-ketosis prone, maturity onset or adult type which cannot be controlled by proper dietary management and exercise, or when insulin therapy is not appropriate.
Dosage/Direction for Use
There is no fixed dosage regimen for the management of diabetes mellitus with APO-GLICLAZIDE (gliclazide) or any other hypoglycemic agent. Determination of the proper dosage for APO-GLICLAZIDE for each patient should be made on the basis of frequent determinations of blood glucose during dose titration and throughout maintenance.
The recommended daily dosage of APO-GLICLAZIDE (gliclazide) is 80 to 320 mg (1 to 4 tablets). Dosages of 160 mg and above should be divided into two equal parts for twice a day administration. APO-GLICLAZIDE should be taken preferentially with meals.
The recommended starting dose of APO-GLICLAZIDE is 1 tablet per day (80 mg) taken as one tablet a day with meals. The total daily dose should not exceed 320 milligrams. The dosage is usually adjusted in increments of 1 tablet depending on the glycaemia response.
Each dosage increment should be separated by at least 14 days.
High-risk subjects: Subjects over the age of 65 years: Begin the treatment with 1/2 tablet taken once a day; This dosage may be progressively increased until satisfactory glucose control is obtained in the patient, provided that an interval of at least 14 days is maintained after each dosage increase and blood sugar levels are monitored closely.
In other high-risk patients: In patients who are undernourished or with a marked change in their general state or whose calorie intake is irregular, and in patients with renal or hepatic insufficiency, treatment must be initiated at the lowest dose and the guidelines for dosage increases scrupulously respected, so as to avoid any hypoglycaemic reactions.
Patients receiving other oral hypoglycaemic agents: As with all hypoglycaemic sulfonylureas, this drug may replace other anti-diabetic treatments without any transition period. On changing from a hypoglycaemic sulphonylurea with a longer half-life (e.g. chlorpropamide) to this drug, patients should be closely monitored (over several weeks) to avoid occurrence of hypoglycaemia, due to the possibility of an overlap of therapeutic effects.
In patients where on initial trial the maximal recommended dose falls to lower blood glucose adequately, the drug should be discontinued. During the course of therapy a loss of effectiveness may occur.
It is advisable to ascertain the contribution of the drug in control of the blood glucose by discontinuing the medication semi-annually or at least annually with careful monitoring of the patient. If the need for the drug is not evident, the drug should not be resumed. In some diabetic subjects, short term administration periods of the drug may be sufficient during periods of transient loss of blood sugar controls.
Patients Receiving Insulin: Maturity onset diabetics with no ketoacidosis or history of metabolic decompensation and whose insulin requirements are less than 40 units per day may be considered for APO-GLICLAZIDE therapy. If a change from insulin to APO-GLICLAZIDE is contemplated in such a patient, discontinue insulin for a period of 2 or 3 days to determine whether any therapy other than dietary regulation and exercise is needed. During this insulin free interval, test the patient's urine at least 3 times a daily for glucose and ketone bodies and monitor the results carefully. The appearance of significant ketonuria accompanied by glucosuria within 12 to 24 hours after the withdrawal of insulin, strongly suggests that the patient is ketosis prone, and precludes the change from insulin to sulfonylurea therapy.
Symptoms: Overdosage with sulfonylureas may result in hypoglycemia but it should be noted that the dosage which causes such hypoglycemia varies widely and may be within the accepted therapeutic range in sensitive individuals.
The manifestations of hypoglycemia include sweating, flushing or pallor, numbness, chilliness, hunger, trembling, headache, dizziness, increased pulse rate, palpitations, increased blood pressure and apprehensiveness in mild cases. The patient should be closely monitored until the doctor is sure that he/she is out of danger. In more severe cases, coma appears.
However, symptoms of hypoglycemia are not necessarily as typical as those described previously and sulfonylureas may cause insidious development of symptoms mimicking cerebrovascular insufficiency.
Treatment: Discontinue medication and treat hypoglycemia by giving dextrose promptly and in sufficient quantity.
If a hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of a concentrated glucose solution (50%). This should be followed by a continuous infusion of a more diluted glucose solution (10%) at a rate necessary to maintain blood glucose levels above 100 mg/dL. The patient should be monitored closely for at least 48 hours. Depending on the state of the patient at this time, the doctor should decide whether additional monitoring is required.
Some sulfonylurea-induced hypoglycemias may be refractory to treatment and susceptible to relapse especially in elderly or malnourished patients. Continuous dextrose infusions for hours or days have been necessary.
Known hypersensitivity or allergy to APO-GLICLAZIDE (gliclazide). Unstable and/or insulin dependent diabetes mellitus, ketoacidosis, coma. During stress conditions such as serious infection, trauma or surgery. In the presence of liver disease or renal impairment. Pregnancy, breast feeding and treatment with miconazole.
The use of gliclazide will not prevent the development of complications peculiar to diabetes mellitus.
Use of gliclazide must be considered as treatment in addition to proper dietary regimen and not as substitute for diet.
Patients over a period of time, may become progressively less responsive to therapy with oral hypoglycemic agents because of worsening of their diabetic state. If a loss of adequate blood glucose-lowering response to gliclazide is detected, the drug should be discontinued.
Special Precautions
Patient Selection and Follow up: Careful selection of patients is important. It is imperative that there be rigid attention to diet, careful adjustment of dosage and instruction of the patient on hypoglycemic reactions, their recognition, remedies and control as well as regular, thorough medical follow-up.
Since the effects of oral hypoglycemic agents on the vascular changes and other long-term sequelae of diabetes mellitus are not fully known, patients receiving such drugs must be closely observed for both short- and long-term complications. Periodic assessment of cardiovascular, ophthalmic, renal and hepatic status is advisable.
In patients stabilized on gliclazide therapy, loss of blood sugar control may occur in cases of acute intercurrent disease or in stressful situations such as trauma or surgery. Under these conditions, discontinuation of gliclazide and administration of insulin should be considered.
The metabolism and excretion of sulfonylureas including gliclazide, may be slowed in patients with impaired renal and/or hepatic function. If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted. In such patients, blood and urine glucose should be regularly monitored.
Hypoglycemic Reactions: As with other sulfonylurea drugs, manifestations of hypoglycemia including dizziness, lack of energy, drowsiness, headache and sweating have been observed and weakness, nervousness, shakiness and paresthesia have also been reported. Severe hypoglycemia can be induced by all sulfonylurea drugs. Particularly susceptible are elderly subjects, patients with impaired hepatic or renal function, those who are debilitated or malnourished and patients with primary or secondary adrenal insufficiency. Hypoglycemia is more likely to occur when caloric intake is inadequate or after strenuous or prolonged physical exercise.
Use in lactation: Some sulfonylurea drugs are excreted in human milk although it is not known whether gliclazide is one of them. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Use in children: Safety and effectiveness in children have not been established.
Use In Pregnancy & Lactation
Nursing Mothers: Some sulfonylurea drugs are excreted in human milk although it is not known whether gliclazide is one of them. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
Adverse Reactions
In clinical trials involving about 2000 patients treated with gliclazide, the overall incidence of adverse reaction was 10.5%, this necessitated the discontinuation of therapy in 1.2% of patients.
Hypoglycemia (See Precautions): As with other sulfonylurea drugs, manifestations of hypoglycemia including dizziness, lack of energy, drowsiness, headache and sweating have been observed. Weakness, nervousness, shakiness and paresthesia have also been reported. Severe hypoglycemia which mimics acute CNS disorders may occur. Hepatic and/or renal disease, malnutrition, debility, advanced age, alcoholism, adrenal or pituitary insufficiency may be predisposing factors.
Gastrointestinal Reactions: Nausea, vomiting, diarrhea, epigastric fullness and gastric irritation can be observed. These reactions are generally dose-related and may disappear when the dose is reduced.
Hepatobiliary Reactions: Rare cases of jaundice have been reported.
Dermatological Reactions: Allergic reactions such as pruritus, erythema, urticaria and morbiliform or maculopapular rash have been reported. These reactions may persist during treatment, which must then be interrupted. Cases of cutanea porphyria tarda and of photosensitivity have also been described with sulfonylurea drugs.
Hematological Reactions: As with all hypoglycemic sulfonylurea drugs, a few rare cases have been reported of leukopenia, agranulocytosis, thrombocytopenia and anemia.
Metabolic Reactions: Cases of hepatic porphyria and disulfiram-like reactions have been described with sulfonylurea drugs. Clinical experience to date has shown that gliclazide has a low incidence of disulfiram type reactions.
Endocrine Reactions: A decrease in the uptake of radioactive iodine by the thyroid gland has been reported with other sulfonylurea drugs. This has not been shown with gliclazide during a study involving 15 patients.
Laboratory Tests: The pattern of laboratory tests abnormalities observed with gliclazide was similar to that for other sulfonylureas. Occasional mild to moderate elevations of SGOT, LDH and creatinine and decrease in natremia have been observed. These abnormalities frequently encountered with treated or untreated diabetic patients are rarely associated with clinical symptoms and generally not considered to be drug related.
Drug Interactions
As a result of drug interaction, hypoglycemia may be potentiated when a sulfonylurea is used concurrently with agents such as: long-acting sulfonamides, tuberculostatics, phenylbutazone, clofibrate, monoamine oxidase inhibitors, coumarin derivatives, salicylates, probenecid, propranolol, miconazole, cimetidine, disopyramide, beta adrenergic blocking agents, tetracycline compounds, chloramphenicol and angiotensin converting enzyme inhibitors.
It may be diminished by corticosteroids, oral contraceptives, thiazide diuretics, phenothiazine derivatives, thyroid hormones and abuse of laxatives etc.
Certain drugs tend to induce hyperglycemia and may lead to loss of control of blood sugar control. These include diuretics (thiazides, furosemide), corticosteroids, oral contraceptives (estrogen plus progestogen) and nicotinic acid in pharmacologic doses.
Barbiturates should be used with caution in patients receiving an oral hypoglycemic agent since they may reduce the hypoglycemic effect.
Intolerance to alcohol (disulfiram-like reaction: flushing, sensation of warmth, giddiness, nausea and occasionally tachycardia) may occur in patients treated with a sulfonylurea. This reaction can be prevented by avoiding the use of alcohol.
APO-GLICLAZIDE (gliclazide) should be stored at room temperature (15-30°C). Preserve in well closed containers.
MIMS Class
ATC Classification
A10BB09 - gliclazide ; Belongs to the class of sulfonylureas. Used in the treatment of diabetes.
Tab 80 mg (round, white, flat-faced bevelled-edge, engraved "APO" over "80" on one side, cross-scored on the other side) x 100's. MR tab 30 mg x 30's, 100's.
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