Gliclazide 80mg Tablets
4.2 Posology and method of administration
Posology
Initial dose
The total daily dose may vary from 40 to 320 mg taken orally. The dose should be adjusted according to the individual patient’s response, commencing with 40 - 80mg daily (A to 1 tablets) and increasing until adequate control is achieved. A single dose should not exceed 160mg (2 tablets). When higher dose is required, Gliclazide should be taken twice daily and according to the main meals of the day.
In obese patients or those not showing adequate response to Gliclazide alone, additional therapy may be required.
♦ Switching from another oral antidiabetic agent to Gliclazide 80 mg tablets: Gliclazide 80 mg tablets can be used to replace other oral antidiabetic agents.
The dosage and the half-life of the previous antidiabetic agent should be taken into account when switching to Gliclazide 80 mg tablets.
A transitional period is not generally necessary. A starting dose of 40-80 mg (‘A to 1 tablet) should be used and this should be adjusted to suit the patient's blood glucose response, as described above.
When switching from a hypoglycaemic sulfonylurea with a prolonged half-life, a treatment free period of a few days may be necessary to avoid an additive effect of the two products, which might cause hypoglycaemia.
♦ Combination treatment with other antidiabetic agents:
Gliclazide 80 mg tablets can be given in combination with biguanides, alpha glucosidase inhibitors or insulin.
In patients not adequately controlled with Gliclazide 80 mg tablets, concomitant insulin therapy can be initiated under close medical supervision.
Special Populations
Elderly:
Gliclazide 80 mg tablets should be prescribed using the same dosing regimen recommended for patients under 65 years of age.
Patients with renal impairment
In patients with mild to moderate renal insufficiency, the same dosing regimen can be used as in patients with normal renal function with careful patient monitoring. These data have been confirmed in clinical trials.
Patients at risk of hypoglycaemia
♦ undernourished or malnourished,
♦ severe or poorly compensated endocrine disorders (hypopituitarism, hypothyroidism, adrenocorticotrophic insufficiency),
♦ withdrawal of prolonged and/or high dose corticosteroid therapy,
♦ severe vascular disease (severe coronary heart disease, severe carotid impairment, diffuse vascular disease).
It is recommended that the minimum daily starting dose of 40-80 mg is used.
Paediatric population
The safety and efficacy of gliclacide in children and adolescents have not been established. No data are available.
4.3 Contra-indications
This medicine is contra indicated in case of
• Hypersensitivity to gliclazide or to any of the excipients listed in section 6.1, other sulfonylureas, sulfonamides,
• type 1 diabetes,
• diabetic pre-coma and coma, diabetic keto-acidosis,
• severe renal or hepatic insufficiency: in these cases the use of insulin is recommended,
• treatment with miconazole (see section 4.5),
• lactation (see section 4.6).
4.4 Special warnings and special precautions for use
Hypoglycaemia:
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 hypoglycaemia if a meal is taken late, if an inadequate amount of food is consumed or if the food is low in carbohydrate. Hypoglycaemia is more likely to occur during low-calorie diets, following prolonged or strenuous exercise, alcohol intake or if a combination of hypoglycaemic agents is being used.
Hypoglycaemia may occur following administration of sulfonylureas (see section 4.8). Some cases may be severe and prolonged. Hospitalisation 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 hypoglycaemic episodes.
Factors which increase the risk of hypoglycaemia:
• patient refuses or (particularly in elderly subjects) is unable to co-operate,
• 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 80 mg Tablets,
• certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency,
• concomitant administration of certain other medicines (see section 4.5).
Renal and hepatic insufficiency:
The pharmacokinetics and/or pharmacodynamics of gliclazide may be altered in patients with hepatic insufficiency or severe renal failure. A hypoglycaemic episode occurring in these patients may be prolonged, so appropriate management should be initiated.
Patient information:
The risks of hypoglycaemia, together with its symptoms (see section 4.8), 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: fever, trauma, infection or surgical intervention. In some cases, it may be necessary to administer insulin.
The hypoglycaemic 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.
Laboratory tests:
Measurement of glycated haemoglobin levels (or fasting venous plasma glucose) is recommended in assessing blood glucose control. Blood glucose self-monitoring may also be useful.
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Treatment of patients with G6PD-deficiency with sulfonylurea agents can lead to haemolytic anaemia. Since gliclazide belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD-deficiency and a non-sulfonylurea alternative should be considered.
4.5 Interactions with other medicinal products and other forms of interaction
The following products are likely to increase the risk of hypoglycaemia Contra-indicated combination
• Miconazole (systemic route, oromucosal gel): increases the hypoglycaemic effect with possible onset of hypoglycaemic symptoms, or even coma.
Combinations which are not recommended
• Phenylbutazone (systemic route): increases the hypoglycaemic effect of sulfonylureas (displaces their binding to plasma proteins and/or reduces their elimination).
It is preferable to use a different anti-inflammatory agent, or else to warn the patient and emphasise the importance of self-monitoring. Where necessary, adjust the dose during and after treatment with the anti-inflammatory agent.
• Alcohol: increases the hypoglycaemic reaction (by inhibiting compensatory reactions) that can lead to the onset of hypoglycaemic coma.
Avoid alcohol or medicines containing alcohol.
Combinations requiring precautions for use
Potentiation of the blood glucose lowering effect and thus, in some instances, hypoglycaemia may occur when one of the following drugs is taken: other antidiabetic agents (insulins, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, GLP-1 receptor agonists), beta-blockers, fluconazole, angiotensin converting enzyme inhibitors (captopril, enalapril), H2-receptor antagonists, MAOIs, sulfonamides, clarithromycin and nonsteroidal antiinflammatory agents.
The following products may cause an increase in blood glucose levels
Combination which is not recommended
• Danazol: diabetogenic effect of danazol.
If the use of this active substance cannot be avoided, warn the patient and emphasise the importance of urine and blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic agent during and after treatment with danazol.
Combinations requiring precautions during use
• Chlorpromazine (neuroleptic agent): high doses (>100 mg per day of chlorpromazine) increase blood glucose levels (reduced insulin release).
Warn the patient and emphasise the importance of blood glucose monitoring. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with the neuroleptic agent.
• Glucocorticoids (systemic and local route: intra-articular, cutaneous and rectal preparations) and tetracosactrin: increase in blood glucose levels with possible ketosis (reduced tolerance to carbohydrates due to glucocorticoids).
Warn the patient and emphasise the importance of blood glucose monitoring, particularly at the start of treatment. It may be necessary to adjust the dose of the antidiabetic active substance during and after treatment with glucocorticoids.
• Ritodrine, salbutamol, terbutaline: (I.V.)
Increased blood glucose levels due to beta-2 agonist effects.
Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin.
Combination which must be taken into account
• Anticoagulant therapy (Warfarin ...):
Sulfonylureas may lead to potentiation of anticoagulation during concurrent treatment.
Adjustment of the anticoagulant may be necessary.