Gliclazide 80mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Gliclazide 80mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Gliclazide 80mg
3 PHARMACEUTICAL FORM
Tablet
Gliclazide Tablets BP are white, circular tablets with GZ80 and a breakline on one face and CP on the other
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Non insulin-dependent diabetes mellitus
4.2. Posology and Method of Administration
For oral administration Adults
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 40-80 mg daily (1/2 - 1 tablet) and increasing until adequate control is achieved. A single dose should not exceed 160 mg (two tablets). When higher doses are required, gliclazide tablets should be taken twice daily 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.
Elderly
Plasma clearance of gliclazide is not altered in the elderly and steady state plasma levels can therefore be expected to be similar to those in adults under 65 years. Clinical experience in the elderly to date shows that gliclazide is effective and well tolerated. However, care should be exercised when prescribing sulphonylureas in the elderly due to a possible age-related increased risk of hypoglycaemia.
Renal and hepatic impairment
The starting dose should be 40mg daily ('A tablet) increasing until adequate control is achieved.
Children
As with other sulphonylureas, gliclazide is not indicated for the treatment of juvenile onset diabetes mellitus.
4.3. Contraindications
Known hypersensitivity to gliclazide, other sulphonylureas and related drugs.
Juvenile onset diabetes
Ketoacidosis.
Severe infection, stress, trauma, surgical procedures or other severe conditions where the drug is unlikely to control the hyperglycaemia.
Severe impairment of renal or hepatic function.
Porphyria.
Diabetic coma and pre-coma.
Pregnancy.
4.4. Special warnings and precautions for use
Hypoglycaemia: all sulphonylurea drugs are capable of producing moderate or severe
hypoglycaemia, particularly in the following conditions:
• In patients controlled by diet alone.
• In cases of overdose.
• When calorie or glucose intake is insufficient
• In patients with irregular mealtimes and/or missed meals
• During excessive exercise
• In elderly or debilitated patients
• In patients with hepatic and/or renal impairment. However, in long-term clinical trials patients with renal insufficiency have been treated satisfactorily using gliclazide at reduced doses with careful patient monitoring.
• In patients with adrenal or pituitary insufficiency
• In patients with hypothyroidism or hyperthyroidism which is not optimally controlled
In order to reduce the risk of hypoglycaemia it is therefore recommended:
• To initiate treatment for non-insulin dependent diabetics by diet alone, if this is possible.
• To take into account the age of the patient: blood sugar levels not strictly controlled by diet alone might be acceptable in the elderly.
• To adjust the dose of gliclazide according to the blood glucose response and to the 24 hour urinary glucose during the first days of treatment
Dosage adjustment may be necessary:
• On the occurrence of mild symptoms of hypoglycaemia (sweating, pallor, hunger pangs, tachycardia, sensation of malaise). Such findings should be treated with oral glucose and adjustment made in drug dosage and/or meal patterns.
• On the occurrence of severe hypoglycaemic reactions (coma or neurological impairment, (see overdose).
• On loss of control of blood glucose (hyperglycaemia). When a patient is stabilised on any diabetic regimen is exposed to stress such as fever, trauma, infection or surgery, a loss of control may occur. At such time, it may be necessary to increase progressively the dosage of gliclazide and if this is insufficient, to discontinue treatment with gliclazide and to administer insulin.
As with other sulphonylureas, hypoglycaemia will occur if the patients’ dietary intake is reduced or if they are receiving a larger dose of gliclazide than required
Patients with rare hereditary problems of galactose intolerance, the Lapp lactase
deficiency or glucose-galactose malabsorption should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interactions
Alcohol may enhance the hypoglycaemic effect of gliclazide.
Analgesics and anti-inflammatory agents: Large doses of salicylates and possibly other NSAIDs may lower blood glucose levels and the gliclazide dose may need to be reduced. Azapropazone and phenylbutazone may enhance the hypoglycaemic effect of gliclazide
Antibacterials: Isoniazid may increase blood sugar levels, so the dose of sulphonylurea may need to be adjusted. Chloramphenicol, co-trimoxazole, sulphonamides and tetracyclines may enhance the hypoglycaemic effect of gliclazide. Rifamycins may reduce the hypoglycaemic effect of sulphonylureas.
Anticoagulants: Anticoagulants and disopyramide may enhance the hypoglycaemic effect of gliclazide. The anticoagulant effects of warfarin and other coumarins may be changed.
Antidepressants: MAOIs may enhance the hypoglycaemic effect of gliclazide.
Antifungals: Miconazole increases plasma concentrations of sulphonylureas. Fluconazole may enhance the hypoglycaemic effect of sulphonylureas.
Anti-gout agents: Enhanced hypoglycaemic effect with allopurinol, sulphinpyrazone and probenecid.
Antihypertensives: ACE Inhibitors, such as captopril and enalapril, may enhance the hypoglycaemic effect of gliclazide. Diazoxide may reduce the hypoglycaemic effect of sulphonylureas. Beta blockers may reduce the hypoglycaemic effects of sulphonylureas and mask the symptoms of hypoglycaemia.
Antimalarials: Possible increase in hypoglycaemia with quinine and quinidine
Antipsychotics: Chlorpromazine in daily doses of 100mg or more can reduce the hypoglycaemic effect of sulphonylureas.
Antiulcer drugs: Cimetidine and ranitidine may enhance the hypoglycaemic effect of gliclazide.
Cytotoxic drugs: Crisantaspase may induce hyperglycaemia and the dose of gliclazide may need to be adjusted.
Diuretics: Loop and thiazide diuretics may reduce the hypoglycaemic effect of sulphonylureas.
Lipid-lowering drugs: Clofibrate group drugs may improve glucose tolerance and have an additive effect.
Lithium: May occasionally impair glucose tolerance.
Sex hormones, hormone antagonists and steroids: Testosterone, and anabolic steroids may enhance the hypoglycaemic effect of gliclazide. Oestrogens, progesterones, oral contraceptives and corticosteroids may reduce the hypoglycaemic effect of sulphonylureas. Octreotide may cause hypoglycaemia or hyperglycaemia.
Thyroid hormones: May reduce the effect of sulphonylureas.
4.6. Pregnancy and Lactation
Gliclazide is contraindicated in pregnancy.
It has not been established whether gliclazide is transferred to human milk. However, some sulphonylureas are excreted in breast milk and this class of drug should be avoided during lactation.
4.7. Effects on Ability to Drive and Use Machines
Patients should be informed that their concentration might be affected if their diabetes is not satisfactorily controlled, especially at the beginning of treatment. (See Special Warnings and Precautions for Use.)
4.8 Undesirable effects
Gastrointestinal disorders: Mild gastrointestinal disturbances including nausea, dyspepsia, heartburn, diarrhoea and constipation have been reported, but this type of adverse reaction can be avoided if gliclazide is taken during a meal. Vomiting, metallic taste, abdominal pain, increased appetite, loss of appetite and weight gain may occur.
Hepatobiliary disorders: Abnormalities of hepatic function are not uncommon during gliclazide therapy. There are rare reports of hepatic failure, hepatitis and jaundice following treatment with gliclazide.
Immune system disorders: Hepatitis, altered liver enzymes, cholestatic jaundice, skin eruptions including rash, bullous eruptions including erythema multiforme, Stevens-Johnson syndrome, erythema nodosum, exfoliative dermatitis, photosensitivity, pruritus, urticaria, fever, blood dyscrasias including agranulocytosis, aplastic and haemolytic anaemia, pancytopenia, leucopenia, thrombocytopenia and neutropenia. Hypersensitivity reactions affecting the skin usually occur within the first six weeks of treatment with a sulphonylurea.
Metabolism and nutrition disorders: Hypoglycaemia (see 4.4 Special warnings and special precautions for use). Sulphonylureas, including gliclazide, may occasionally induce a syndrome of inappropriate secretion of antidiuretic hormone, characterised by water retention and hyponatraemia.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.
4.9 Overdose
Symptoms: hypoglycaemia.
Treatment:
■ Patient should be transferred to hospital
■ Activated charcoal to be administered
■ Hypoglycaemia should be treated with urgency by appropriate means
■ Vital signs should be monitored and appropriate supportive measures used, including the treatment of cerebral oedema should this occur
■ Observation should continue for several days in case hypoglycaemia is prolonged or recurs.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Gliclazide is an oral hypoglycaemic sulphonylurca which stimulates the release of insulin from pancreatic P-cells, probably by facilitating Ca2+ transport across the P-cell membranes. The effect of gliclazide on increasing the secretion of insulin is most marked in the early phases of the response to a rise in plasma glucose. Nevertheless, hypoglycaemic effects can be shown even without any increase in the plasma levels of insulin. Like other sulphonylureas, it exerts an important hypoglycaemic effect on the cell surface at one or more postbinding sites, although there is evidence that there may sometimes be an increase in insulin receptors. The sulphonylureas also have an important hypoglycaemic action by decreasing hepatic glucose output, and it has recently been shown that the sulphonylureas, including gliclazide, stimulate the most potent activator of liver phosphofructokinase at concentrations which are found in the blood of treated diabetic patients. This would help to explain the extrapancreatic action of the sulphonylureas of inhibiting hepatic gluconeogenesis through phosphofructokinase and fructose diphosphatase activities and also the reduction of insulin resistance in noninsulin dependent diabetes.
In man, apart from having similar hypoglycaemic effect to other sulphonylureas, gliclazide has been shown to reduce platelet adhesiveness and increase fibrinolytic activity. Those factors are thought to be implicated in the pathogenesis of long term complications of diabetes mellitus.
5.2. Pharmacokinetic Properties
The speed of absorption from the gastrointestinal tract varies considerably, and individuals can be classified as slow or fast absorbers, although the apparent difference may depend more on first-pass metabolism than absorption rate. For an 80mg dose in normal volunteers the average time to maximum is four hours and maximum concentration 3.9mg l -1. Presystemic metabolism has not been properly studied, but the low plasma clearance (13 ml.min-1) suggests it is not significant. The mean plasma half life is 10 hours and the volume of distribution is about 25L. About 95% (85-97%) of gliclazide is bound to protein in plasma, mostly to albumin. Ethyl alcohol has been shown to reduce the binding to albumin, possibly explaining an enhanced hypoglycaemic effect. It may also be important that non-enzymatic glycolization of human serum albumin induced by chronic hyperglycaemia markedly decreases its binding to sulphonylureas, thus increasing the proportion of free and active drug.
No studies have reported the presence of gliclazide in human breast milk.
5.3. Preclinical Safety Data
There are no pre-clinical data of relevance to the prescriber which are additional to those included in other sections.
6 PHARMACEUTICAL PARTICULARS
6.1
List of excipients
Maize Starch Lactose
Polyvinylpyrrolidone Magnesium Stearate
6.2. Incompatibilities
None.
6.3. Shelf Life
36 months.
6.4. Special Precautions for Storage
Do not store above 25°C.
6.5. Nature and Contents of Container
PVC/aluminium blister packs of 28, 30, 56 or 60 tablets in cartons.
6.6 Special precautions for disposal
None stated.
7. Marketing Authorisation Holder
Wockhardt UK Limited Ash Road North Wrexham LL13 9UF United Kingdom
8. Marketing Authorisation Number
PL 29831/0103
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
14/03/2007
10 DATE OF REVISION OF THE TEXT
27/08/2015