Gliclazide Mr 30 And 60 Ascend 30 mg & 60 mg MR tablets

Gliclazide MR Ascend is indicated in type 2 diabetic patients, in association with dietary measures, lifestyle changes and exercise, when dietary measures, lifestyle and exercise alone are not sufficient to control blood glucose.

Posology: For adult use only: Gliclazide MR 30 Ascend: The daily dose may vary from 1 to 4 tablets a day i.e. 30 mg to 120 mg taken as a single daily dose. Gliclazide MR 60 Ascend: The daily dose may vary from half to 2 tablets a day i.e. 30 mg to 120 mg taken as a single daily dose. If a dose is forgotten, the dose taken on the next day should not be increased. The dose should be adjusted according to the individual patientu2019s metabolic response (blood glucose levels and/or glycosylated haemoglobin HbA1C). Initial dose: The initial recommended dose is 30 mg once daily, taken with breakfast. Dose adjustments: If fasting blood glucose levels have not decreased satisfactorily, the dosage can be increased progressively to 60 mg, 90 mg, or 120 mg per day, by successive increments, respecting an interval of at least one month between each increment, except in patients whose blood glucose levels have not decreased after 15 days of treatment. In this case, it is possible to propose a dosage increase at the end of the 2nd week of treatment. The daily dose should not exceed 120 mg. Previously untreated patients should commence with a dose of 30 mg. Replacement of immediate release gliclazide 80 mg with Gliclazide MR Ascend: In patients stabilised on gliclazide 80 mg, the replacement of gliclazide 80 mg by Gliclazide MR Ascend may initially be based on: 1 tablet of immediate release gliclazide 80 mg = 1 tablet of Gliclazide MR 30 Ascend. Replacement of another sulphonylurea with Gliclazide MR Ascend: Gliclazide MR Ascend can replace other sulphonylurea treatment. For the transition to Gliclazide MR Ascend, the dosage and the half-life of the previous oral hypoglycaemic medicine must be considered. If a patient is changed from another oral sulphonylurea with a prolonged half-life, a therapeutic window of a few days may prove to be necessary to avoid the additive effect of the two products and the subsequent risk of hypoglycaemia. During such a changeover, it is recommended to follow the same procedure as for the initiation of the treatment with Gliclazide MR Ascend, i.e. to initiate treatment with a dose of 30 mg per day and then increase the dosage by increments, according to the metabolic evolution of each patient. Association with other oral antidiabetic medicines: Gliclazide MR Ascend, can be given in combination with alpha glucosidase inhibitors or insulin, but in that case, diabetic control should be checked with blood sugar readings, because of the possibility of hypoglycaemia. In combined therapy with biguanides, there may be a greater risk of cardiovascular mortality than with the use of Gliclazide MR Ascend alone.

Special populations Elderly patients and patients with renal failure: The efficacy and tolerance of Gliclazide MR Ascend, prescribed using the same therapeutic regimen in subjects over 65 years and patients with mild to moderate renal failure (creatinine clearance 30 u2013 80 mL/min) has been confirmed in clinical trials. The dosage will therefore be identical to that recommended for adults under the age of 65 years, and for patients with normal renal function, with careful patient monitoring. Use of Gliclazide MR Ascend, is contraindicated in patients with severe renal impairment (see section 4.3). Patients at risk of hypoglycaemia: u2022 undernourished or malnourished, u2022 severe or poorly compensated endocrine disorders (hypopituitarism, hypothyroidism, adrenocorticotrophic insufficiency), u2022 withdrawal of prolonged and/or high dose corticosteroid therapy, u2022 severe vascular disease (severe coronary heart disease, severe carotid impairment, diffuse vascular disease). It is recommended that the minimum daily starting dose of 30 mg is used. Paediatric population: Gliclazide MR Ascend should not be used in children (see section 4.3). Method of administration Gliclazide MR Ascend should be given orally, with meals (breakfast).

Gliclazide MR Ascend is contraindicated in: u2022 patients with hypersensitivity to gliclazide, other sulphonylureas, sulphonamides, or to any, or to any of the excipients of Gliclazide MR Ascend, listed in section 6.1. u2022 Type 1 diabetes (Juvenile Insulin Dependent Diabetes Mellitus), diabetic keto-acidosis, and diabetic pre-coma and coma, u2022 Children, u2022 Severe renal or hepatic insufficiency, u2022 Treatment with miconazole (see Section 4.5), u2022 Pregnancy, u2022 Lactation.

Increased risk of cardiovascular mortality: The administration of oral hypoglycaemics, including Gliclazide MR Ascend, may be associated with increased cardiovascular mortality, as compared to treatment with diet alone or diet with insulin. Hypoglycaemia: Hypoglycaemia may occur following administration of sulphonylureas including Gliclazide MR Ascend (see section 4.8). Some cases may be severe and prolonged. A reduction in dosage may be necessary in patients with mild to moderate renal dysfunction. (See sections 4.2 and 4.3).

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 favouring hypoglycaemia include: u2022 Patient refusing or (particularly elderly patients) being unable to co-operate, u2022 Malnutrition, irregular mealtimes, skipping meals, periods of fasting or dietary changes, u2022 Imbalance between physical exercise and carbohydrate intake, u2022 Certain endocrine disorders: thyroid disorders, hypopituitarism and adrenal insufficiency. These disorders should be controlled by appropriate therapy before introducing Gliclazide MR Ascend, u2022 Concomitant administration of certain other medicines (see section 4.5), u2022 Deterioration in renal function. u2022 Severe hepatic insufficiency This treatment should only be prescribed if the patient is likely to have a regular food intake (including breakfast). Hypoglycaemia is more likely to occur during periods of low-calorie diet, irregular carbohydrate intake, following prolonged or strenuous exercise, following alcohol intake or during the administration of a combination of hypoglycaemic medicines. Symptoms of hypoglycaemia usually disappear after absorption of carbohydrates (sugar). However, despite initial effective measures, hypoglycaemia may occur. Artificial sweeteners have no effect on hypoglycaemia. In the case of severe prolonged hypoglycaemia, immediate medical treatment and even hospitalisation is necessary.

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, 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. Johnu2019s Wort (Hypericum perforatum) preparations (see section 4.5), fever, trauma, infection or surgical intervention. In some cases, it may be necessary to administer insulin. The hypoglycaemic effect of Gliclazide MR Ascend, 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. Dysglycaemia: Disturbances in blood glucose, including hypoglycaemia and hyperglycaemia 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 MR Ascend and a fluoroquinolone.

The following products are likely to increase the risk of hypoglycaemia: Contraindicated combinations: u2022 Miconazole, (systemic route, oral gel): increases the hypoglycaemic effect with possible onset of hypoglycaemic symptoms, or even coma. (See section 4.3). Combinations which are not recommended: u2022 Phenylbutazone (systemic route): increases the hypoglycaemic effect of sulphonylureas, u2022 Alcohol: Avoid intake of alcohol or medicine 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 medicines is taken: Fluconazole, ketoconazole (systemic route, oral gel), beta-blockers, other antidiabetic medicines (insulin, acarbose, metformin, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide (GLP)-1 receptor agonists, biguanides), ACE-inhibitors (captopril, enalapril), sulphonamides, H2-receptor antagonist (cimetidine, ranitidine), non-steroidal anti-inflammatory medicines (NSAIDS), mono-amine-oxidase (MAO) inhibitors, clarithromycin and chloramphenicol. The following products may cause an increase in blood glucose level: Combination which is not recommended: u2022 Danazol: diabetogenic effect of danazol. Combinations requiring precautions for use: u2022 Chlorpromazine: (neuroleptic agent): high doses (> 100 mg per day of chlorpromazine) increase blood glucose levels (reduced insulin release), u2022 Glucocorticoids: (systemic and local route: intra-articular, cutaneous, and rectal preparations) and tetracosactrin: increase in blood glucose levels with possible ketosis. u2022 Salbutamol, terbutaline and other beta-adrenergic agonists: increased blood glucose levels due to beta-2 agonist effects. Emphasise the importance of monitoring blood glucose levels. If necessary, switch to insulin. u2022 Ephedrine, pseudoephedrine and common cold medicines. u2022 Saint Johnu2019s Wort (Hypericum perforatum) preparations: Gliclazide exposure is decreased by Saint Johnu2019s Wort (Hypericum perforatum). Emphasise the importance of blood glucose levels monitoring. The following products may cause dysglycaemia: Combinations requiring precautions during use: u2022 Fluoroquinolones: in case of concomitant use of Gliclazide MR Ascend and a fluoroquinolone, the patient should be warned of the risk of dysglycaemia, and the importance of blood glucose monitoring should be emphasised., u2022 Anticoagulant therapy (warfarin): sulphonylureas such as Gliclazide MR Ascend may lead to potentiation of anticoagulation during concurrent treatment. Regular monitoring of the INR.

Pregnancy: Safety of use of Gliclazide MR Ascend has not been established. Thus, Gliclazide MR Ascend is not recommended during pregnancy (see section 4.3). Breastfeeding: Gliclazide MR Ascend must not be used in breastfeeding women as safety has not been established (see section 4.3).

Gliclazide MR Ascend has no known influence on the ability to drive and use machines. Patients should be made aware of the symptoms of hypoglycaemia, and should be careful when driving, or operating machinery, especially at the beginning of treatment.

Tabulated summary of adverse reactions The adverse reactions are sorted by frequencies and be listed by system organ class. Within each frequency grouping, undesirable effects have been presented in order of decreasing seriousness. Frequencies are defined as frequent, less frequent and frequency not known. Class/ Frequency Adverse reaction Gastrointestinal disorders: Frequent Abdominal pain, nausea, vomiting, dyspepsia, diarrhoea, constipation, metallic taste, increased appetite and weight gain. Metabolism and nutrition disorders: Less frequent Anorexia Skin and subcutaneous tissue disorders: Frequent Rash, pruritus Less frequent Urticaria, erythema, maculopapular rashes and bullous reactions, (such as Stevens-Johnson syndrome and toxic epidermal necrolysis), and exceptionally, rash with eosinophilia, and systemic symptoms (DRESS) Frequency unknown Photosensitivity, facial flushing, exfoliative dermatitis and erythema nodusum Blood and lymphatic system disorders: Less frequent Changes may include anaemia, leucopenia, thrombocytopenia, granulocytopenia, aplastic anaemia, haemolytic anaemia. These are in general reversible upon discontinuation of medicine. Hepato-biliary disorders: Less frequent Raised hepatic enzyme levels (AST, ALT, alkaline phosphatase), hepatitis (isolated reports). Discontinue treatment if cholestatic jaundice appears. These symptoms usually disappear after discontinuation of treatment. Eye disorders: Less frequent Transient visual disturbances may occur especially on initiation of treatment, due to changes in blood glucose levels Class attribution effects: As for other sulfonylureas, the following adverse events have been observed: cases of erythroytopenia, agranulocytosis, haemolytic anaemia, pancytopenia, allergic vasculitis, hyponatraemia, elevated liver enzyme levels and even impairment of liver function (e.g. with cholestasis and jaundice) and hepatitis which regressed after withdrawal of the sulphonylurea or led to life-threatening liver failure in isolated cases. The following side-effects have been reported and the frequencies are unknown: Hypoglycaemia: The most frequent adverse reaction with gliclazide is hypoglycaemia. As for other sulfonylureas, treatment with Gliclazide MR Ascend can cause hypoglycaemia, if mealtimes are irregular and, in particular, if meals are skipped. Possible symptoms of hypoglycaemia are: headache, intense hunger, nausea, vomiting, lassitude, sleep disorders, agitation, aggression, poor concentration, reduced awareness and slowed reactions, depression, confusion, visual and speech disorders, aphasia, tremor, paresis, sensory disorders, dizziness, feeling of powerlessness, loss of self-control, delirium, convulsions, shallow respiration, bradycardia, drowsiness and loss of consciousness, possibly resulting in coma and lethal outcome. In addition, signs of adrenergic counter-regulation may be observed: sweating, clammy skin, anxiety, tachycardia, hypertension, palpitations, angina pectoris and cardiac dysrhythmia. Usually, symptoms disappear after intake of carbohydrates (sugar). However, artificial sweeteners have no effect. Experience with other sulfonylurea shows that hypoglycaemia can recur even when measures prove effective initially. If a hypoglycaemic episode is severe or prolonged, and even if it is temporarily controlled by intake of sugar, immediate medical treatment or even hospitalisation is required. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website and must also be reported to Ascend Laboratories (Pty) Ltd. vial the e-mail: [email protected].

An overdose of Gliclazide MR Ascend may cause hypoglycaemia which could be severe and prolonged. Moderate symptoms of hypoglycaemia, without any loss of consciousness or neurological signs, must be corrected by carbohydrate intake, dose adjustment and/or modification of diet. Strict monitoring should be continued until the patient is out of danger. Severe hypoglycaemic reactions, with coma, convulsions or other neurological disorders should be treated as a medical emergency, requiring immediate hospitalisation. If hypoglycaemic coma is diagnosed or suspected, the patient should be given a rapid IV injection of 50 mL of concentrated glucose solution (20 u2013 30 %). This should be followed by continuous infusion of a more dilute solution (10 %), at a rate necessary to maintain blood glucose levels above 5,5 mmol/L. Patients should be monitored closely, long enough to be sure that hypoglycaemia will not re-occur, and, depending on the patientu2019s condition, the doctor will decide if further monitoring is necessary. Dialysis is of no use in these patients due to the strong binding of gliclazide to proteins.