COMPOSITION :
Gliclazide Tablet 80 mg, each tablet contains : Gliclazide 80 mg.
DESCRIPTIONS :
Gliclazide contains Gliclazide as active ingredients is available in tablet 80 mg.
INDICATIONS :
Non-Insulin-dependent diabetes, in association with an adapted diet, in cases where dietary measures alone provide inadequate control of blood glucose levels.
DOSAGE AND ADMINISTRATIONS :
FOR ADULTS ONLY.
As with all hypoglycaemic agents, the dosage must be adapted to suit each individual case.
In the case of a transient disturbance of glucose control, administration of the product for a short period of time may be sufficient in a patient in whom the glucose balance is normally well maintained by dietary measures.
Subjects under the age of 65 years
– Initial dose
The recommended initial dose is 1 tablet per day.
– Dosage increments
The dosage is usually adjusted in increments of 1 tablet depending on the glycaemic response. Each dosage increment should be separated by at least 14 days.
– Maintenance treatment
The dosage varies from 1 to 3 tablets per day, 4 in exceptional cases.
The standard dosage is 2 tablets per day, taken as 2 daily doses.
High-risk subjects
– Subjects over the age of 65 years
- Begin the treatment with ½ 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 (see WARNINGS AND PRECAUTIONS).
– Patients receiving other oral hypoglycaemic agents
As with all hypoglycaemic sulphonylureas, 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 the occurrence of hypoglycaemia, due to the possibility of an overlap of the therapeutic effects.
OVERDOSAGE :
An overdose of sulphonylureas may lead to hypoglycaemia.
Moderate symptoms of hypoglycaemia, with no loss of consciousness or neurological signs, should be completely corrected by the administration of carbohydrates and by adjusting the dosage and/or dietary measures. The patient should be closely monitored until the doctor is sure that he/she is out of danger.
Severe hypoglycaemic reactions, with coma, convulsions or other neurological disorders, are possible and constitute a medical emergency requiring the immediate hospitalization of the patient.
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 dilute 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.
Plasma clearance of Gliclazide may be prolonged in patients suffering from a hepatic disorder. Dialysis is of no value as Gliclazide is highly protein-bound.
CONTRAINDICATIONS :
The use of this medicine is contra-indicated in the following cases :
- Hypersensitivity to Gliclazide or other sulphonylureas or sulphonamides or to any of the excipients used.
- Insulin-dependent diabetes, particularly juvenile diabetes, diabetes complicated by ketosis and acidosis, or diabetic precoma.
- Severe hepatic or renal insufficiency.
- Treatment with Miconazole (see DRUG INTERACTIONS).
- Breast-feeding.
In general, it is not advisable to combine this drug with Phenylbutazone, Danazol (see DRUG INTERACTIONS) or alcohol.
WARNINGS AND PRECAUTIONS :
- Hypoglycaemia : Hypoglycaemia may occur during treatment with hypoglycaemic sulphonylureas. Some cases may be severe and prolonged. Hospitalisation may be required and blood sugar levels should be corrected for several days if necessary.
Careful selection of the patient and the dosage, as well as keeping the patient adequately informed are necessary to avoid episodes of hypoglycaemia.
Patients who are elderly, undernourished or with a change in their general state and patients with adrenal insufficiency or hypopituitarism are particularly sensitive to the hypoglycaemic effects of anti-diabetic agents. Hypoglycaemia may be difficult to diagnose in elderly subjects and patients treated with beta-blockers. - This treatment should only be prescribed if the patient is likely to eat regularly (including breakfast). A regular intake of carbohydrates is important due to the increased risk of hypoglycaemia if meals are taken late, in cases of inadequate diet or if the diet contains an inadequate balance of carbohydrates.
Hypoglycaemia is more likely to occur in subjects following a low-calorie diet, after considerable or prolonged exertion, after the consumption of alcohol or during the administration of a combination of hypoglycaemic agents.
Renal or hepatic insufficiency may alter the distribution of Gliclazide and hepatic insufficiency may also reduce the capacity for gluconeogenesis; these two effects increase the risk of serious hypoglycaemic reactions. - Glycaemic imbalance : Control of blood glucose levels by anti-diabetic agents may be reduced in patients with fever, trauma or infection or in patients undergoing surgery. In these cases, it may be necessary to discontinue the treatment and administer Insulin.
The efficacy of all oral hypoglycaemic agents, including Gliclazide, in lowering blood sugar to the desired level decreases in the long term in many patients. This may be due to an increase in the severity of the diabetes or to a reduced response to the treatment. This phenomenon is known as secondary failure and should be distinguished from primary failure, in which the drug proves to be ineffective when prescribed as first-line treatment for a given patient. Adequate dosage adjustment and observation of the diet must be considered before classing the patient as a secondary failure. - Biological tests : Blood and urinary glucose levels should be monitored periodically. Measurements of glycosylated haemoglobin levels may prove to be useful.
- Renal and hepatic insufficiency : The pharmacokinetics and/or pharmacodynamics of Gliclazide may be altered in patients with renal or hepatic insufficiency. If hypoglycaemia occurs in these patients and there is a risk that it will be prolonged, an appropriate treatment should be instituted.
- Patient information :
- The risks of hypoglycaemia, its symptoms and treatment and the predisposing factors for it, should be explained to the patient and his/her family. Primary or secondary failures of treatment should also be explained (see section headed glycaemic imbalance above).
- The patient should be informed of the potential risks and the benefits of this and other types of treatment. He/she should be informed of the importance of maintaining the prescribed diet, following a regular physical exercise programme and monitoring urinary and/or blood glucose levels regularly.
- Due to the presence of lactose, this drug is contra-indicated in the case of congenital galactosemia, the syndrome of malabsorption of glucose and galactose or a deficit in lactase.
- Pregnancy :
Risk due to diabetes
When poorly controlled, diabetes (gestational or permanent) is responsible for an increase in congenital malformations and perinatal death. The best possible control must be achieved around the time of conception in order to reduce the risk of malformation.
Risk due to Gliclazide
Hypoglycaemic sulphonylureas are teratogenic in animals at high doses. Relevant clinical data is currently insufficient for an evaluation of the possible malformative or foetotoxic effects of Gliclazide when it is administered during pregnancy.
Course of action
Maintaining diabetic control allows pregnancy to progress normally in this category of patients.
Insulin treatment is essential, irrespective of the type of diabetes, I or II, gestational or permanent.
In this last case, a change from oral treatment to Insulin is recommended from the time that pregnancy is planned or if a pregnancy is discovered accidentally in a patient exposed to Gliclazide : In this case it is not automatically necessary to recommend a termination of the pregnancy, but the pregnancy should be monitored with particular care with appropriate prenatal screening.
Neonatal monitoring of blood glucose levels is recommended.
- Breast-feeding :
In the absence of data concerning the passage into breast milk and taking into account the risk of neonatal hypoglycaemia, breast-feeding is contra-indicated during treatment with this drug. - Effect on ability to drive and use machines :
Patients should be made aware of the symptoms of hypoglycaemia and should be careful when driving and operating machines.
DRUG INTERACTIONS :
The following products are likely to increase hypoglycaemia.
Contra-indicated association
– Miconazole (systemic route, oral gel) : Increases the hypoglycaemic effect with possible occurrence of hypoglycaemic symptoms or even coma.
Inadvisable associations
– Phenylbutazone (systemic route) : Increase the hypoglycaemic effect of sulphonylureas (displacement of plasma protein binding and/or decrease in their elimination).
An alternative anti-inflammatory agent with less potential for interaction should preferably be used, otherwise warn the patient and emphasize the need for self-monitoring; if necessary, adjust the dosage of Gliclazide during treatment with the anti-inflammatory agent and after it has been discontinued.
– Alcohol : Antabuse effect, particularly for Chlorpropamide, Glibenclamide, Glipizide, Tolbutamide. Increased hypoglycaemic reaction (inhibition of compensatory mechanisms), which may increase the likelihood of hypoglycaemic coma. Avoid the consumption of alcoholic drinks and medicines containing alcohol.
Combinations requiring precautions
– Beta-blockers :
All beta-blockers mask certain symptoms of hypoglycaemia : Palpitations and tachycardia. Most non-cardioselective beta-blockers increase the incidence and severity of hypoglycaemia.
Inform the patient and encourage self-monitoring of blood glucose levels, particularly at the start of treatment.
– Fluconazole :
Increase in the half-life of the sulphonylurea with the possible occurrence of hypoglycaemic symptoms.
Inform the patient, emphasize the need for self-monitoring of blood glucose levels and, if necessary, adjust the dosage of the sulphonylurea during treatment with Fluconazole.
– Inhibitors of angiotensin converting enzyme (Captopril, Enalapril) :
The use of angiotensin converting enzyme inhibitors may lead to an increase in the hypoglycaemic effect in diabetic patients treated with hypoglycaemic sulphonylurea.
Symptoms of hypoglycaemia appear to be an exceptional occurrence.
One theory put forward is that an improvement in glucose tolerance results in a reduction in Insulin requirements.
Emphasize the need for self-monitoring of blood glucose levels.
The products which may cause an increase in blood sugar levels.
Inadvisable association
– Danazol : (Diabetogenic effect of Danazol)
If the combination is unavoidable, warn the patients of the potential risk and emphasize the need for self-monitoring of blood and urinary glucose levels. If necessary, adjust the dosage of the anti-diabetic agent during treatment with Danazol and after it has been discontinued.
Combinations requiring special precautions
– Chlorpromazine (neuroleptics) : At high doses (100 mg per day of Chlorpromazine) blood sugar levels may be raised (decrease in the release of Insulin).
Inform the patient and emphasize the need for self-monitoring of blood glucose levels. If necessary, adjust the dosage of the anti-diabetic agent during treatment with the neuroleptic and after it has been discontinued.
– Glucocorticoids (gluco-) and Tetracosactin (systemic and local routes : Intra-articular, cutaneous and rectal administration) (excepted Hydrocortisone used as substitute treatment in Addison’s disease).
Rise in blood sugar levels, occasionally with ketosis (decrease in carbohydrate tolerance caused by corticosteroids).
Inform the patient and emphasize the need for self-monitoring of blood glucose levels, particularly at the start of treatment. If necessary, adjust the dosage of the anti-diabetic agent during treatment with corticosteroids and after they have been discontinued.
– Beta-2 sympathomimetics : Ritodrine, Salbutamol, Terbutaline :
Increased blood glucose levels by beta2-stimulants.
Emphasize the need for monitoring of blood glucose levels.
If necessary, change to Insulin treatment.
ADVERSE REACTIONS :
– Hypoglycaemia (see WARNINGS AND PRECAUTIONS and OVERDOSAGE).
– Gastrointestinal disorders, of which the following have been reported : Nausea, dyspepsia, diarrhea and constipation; they may be avoided or alleviated if the Gliclazide is taken during meals or by dividing the doses.
– The following side effects have been reported more rarely :
- Mucous membrane and skin reactions : Rash, pruritus, urticaria, maculopapular rash.
- Haematological effects : Anaemia, leukopenia, thrombocytopenia.
- Increases in ASAT, ALAT, alkaline phosphatase, hepatitis (rare). Discontinue treatment if cholestatic jaundice occurs.
As a general rule, these symptoms disappear when treatment is stopped.
PRESENTATION :
Gliclazide Tablet 80 mg Box, 10 strips @ 10 tablets Reg. No. GKL2102363910A1
STORAGE :
STORE BELOW 30ºC
ON MEDICAL PRESCRIPTION ONLY
Manufactured by :
BERNOFARM
Sidoarjo – Indonesia
