Glibenclamide 5mg Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Glibenclamide 5mg Tablets
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
Glibenclamide 5.0mg
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Tablet
White dragee-shaped tablets marked CP on one face and GL and 5 on either side of a breakline on the other face.
4.1. Therapeutic Indications
Glibenclamide is a hypoglycaemic agent indicated in the treatment of noninsulin dependent diabetes in patients who respond inadequately to dietary measures alone.
4.2. Posology and method of administration
Treatment of previously untreated diabetes:
Stabilisation can be started with one 5mg tablet daily with or immediately after breakfast or the first main meal. If control is satisfactory one tablet is continued as the maintenance dose. If control is unsatisfactory, the dose can be adjusted by increments of 2.5 or 5mg at weekly intervals. The total daily dosage rarely exceeds 15mg and increasing the daily dosage above this does not generally produce any additional effect.
The total daily requirement should normally be given as a single dose at breakfast, or with the first main meal. The patient’s diet and activity should be taken into account.
Children: Glibenclamide is not recommenced for use in children.
In debilitated patients who may be more liable to hypoglycaemia, treatment should be initiated with one 2.5mg tablet daily.
Changeover from other sulphonylureas:
The changeover to glibenclamide from other drugs with similar mode of action can be carried out without any break in therapy.
Treatment is commenced with the equivalent dose of glibenclamide without exceeding an initial dose of 10mg. If response is inadequate, the dose can be raised in a stepwise fashion to 15mg daily. One 5mg tablet of glibenclamide is approximately equivalent to 1g tolbutamide or glymidine, 250mg chlorpropamide or tolazamide, 500mg acetohexamide, 25mg glibornuride or 5mg glipizide.
Changeover from biguanides: The biguanide should be withdrawn and glibenclamide treatment started with one 2.5mg tablet. The dosage should then be adjusted by increments of 2.5mg to achieve control.
Combination with biguanides: If adequate control is not possible with diet and 15mg of glibenclamide, control may be established by combined administration of glibenclamide and a biguanide derivative.
Changeover from insulin:
While it is appreciated that most patients who are on insulin therapy will continue to need it, there may be a few patients, particularly those on low daily doses, who will remain stabilised if transferred from insulin to glibenclamide.
4.3. Contraindications
Known hypersensitivity to glibenclamide, or to any of the excipients Patients known to have sensitivity to other sulphonylureas and related drugs Juvenile onset diabetes Diabetic ketoacidosis.
Severe infection, stress, trauma, surgical procedures or other severe conditions where the drug is unlikely to control the hyperglycaemia.
Severe impairment of renal function.
Hepatic impairment.
Diabetic coma and pre-coma.
Porphyria
Pregnancy
Elderly (> 70 years).
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 debilitated patients
• In patients with mild to moderate renal impairment. However, in longterm clinical trials patients with renal insufficiency have been treated satisfactorily using glibenclamide at reduced doses with careful patient monitoring.
• In patients with adrenal or pituitary insufficiency
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 adjust the dose of glibenclamide according to the blood glucose response and to the 24 hour urinary glucose during the first days of treatment
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 interaction
Concomitant use of glibenclamide with the following medicine should be avoided:
Bosentan: There is the potential for an increased risk of hepatotoxicity when glibenclamide is given with bosentan and therefore concomitant use should be avoided.
The following medicines affect the use of glibenclamide:
Analgesics and anti-inflammatory agents: Large doses of salicylates and possibly other NSAIDs may lower blood glucose levels and the glibenclamide dose may need to be reduced. Azapropazone and phenylbutazone may enhance the hypoglycaemic effect of glibenclamide.
Antibacterials: Isoniazid may increase blood sugar levels, so the dose of sulphonylurea may need to be adjusted. Chloramphenicol, ciprofloxacin, co-trimoxazole, sulphonamides and tetracyclines may enhance the hypoglycaemic effect of glibenclamide. Concomitant use with rifamycins may reduce the hypoglycaemic effect of sulphonylureas.
Cytotoxic drugs: Crisantaspase may induce hyperglycaemia and the dose of glibenclamide may need to be adjusted.
Alcohol: May enhance the hypoglycaemic effect of glibenclamide.
Anticoagulants: Anticoagulants and disopyramide may enhance the hypoglycaemic effect of glibenclamide.
Antidepressants: Tricyclic antidepressants and MAOIs may enhance the hypoglycaemic effect of glibenclamide.
Antifungals: Miconazole increases plasma concentrations of sulphonylureas. There is the potential for fluconazole to increase the plasma concentration of glibenclamide.
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 glibenclamide. Beta blockers may increase the hypoglycaemic effects of sulphonylureas and mask the symptoms of hypoglycaemia. Concomitant use with diazoxide may reduce the hypoglycaemic effect of sulphonylureas.
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 glibenclamide.
Diuretics: Loop and thiazide diuretics may reduce the hypoglycaemic effect of glibenclamide.
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 glibenclamide. Octreotide may cause hypoglycaemia or hyperglycaemia. Concomitant use with oestrogens, progesterones, oral contraceptives, and corticosteroids may reduce the hypoglycaemic effect of sulphonylureas.
Thyroid hormones: May reduce the effect of sulphonylureas.
Glibenclamide affects the use of the following medicines:
Anti-coagulants: The anticoagulant effects of warfarin and other coumarins may be changed.
Immunosuppressants: There is the potential for glibenclamide to raise plasma levels of ciclosporin, which would necessitate a dose reduction of ciclosporin.
4.6. Pregnancy and lactation
Pregnancy
Glibenclamide is contraindicated in pregnancy.
Lactation
It has not been established whether glibenclamide is transferred to human milk. However, some sulphonylureas are excreted in breast milk. Because the potential for hypoglycaemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the benefit of breast-feeding to the infant and the benefit of the drug to the mother.
4.7. Effects on Ability to Drive and Use Machines
None (unless there is a risk of hypoglycaemia).
4.8. Undesirable effects
Immune system disorders
Hypersensitivity reactions:
• Rash, urticaria, erythema multiforme, erythema nodosum, bullous eruptions, pruritus, exfoliative dermatitis, photosensitivity
• Altered liver enzymes values, hepatitis and cholestatic jaundice.
• Blood dyscrasias including agranulocytosis, aplastic and haemolytic anaemia, pancytopenia, leucopenia, thrombocytopenia and neutropenia
• Fever
• Stevens-Johnson syndrome
Hypersensitivity reactions affecting the skin usually occur within the first six weeks of treatment with a sulphonylurea.
Metabolism and nutrition disorders
Hypoglycaemia (see section 4.4).
Syndrome of inappropriate secretion of antidiuretic hormone, characterised by water retention and hyponatraemia.
Gastrointestinal disorders
Nausea, heartburn, anorexia, and diarrhoea. This type of adverse reaction can be avoided if glibenclamide is taken during a meal. Vomiting, metallic taste, increased appetite and weight gain.
Hepatic Disorders
Intrahepatic cholestasis and acute hepatitis-like syndrome.
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.
5.1. Pharmacodynamic Properties
Glibenclamide is an orally active hypoglycaemic agent, which acts by stimulating insulin secretion.
5.2. Pharmacokinetic Properties
Glibenclamide is rapidly absorbed and is extensively bound to plasma proteins, but is not readily displaced by acidic drugs. It is excreted as metabolites in the urine and bile.
5.3. Preclinical Safety Data
There are no pre-clinical data of any relevance to the prescriber, which are additional to those already included in other sections.
6.1. List of Excipients
Lactose Maize Starch Povidone K30 Magnesium stearate
6.2. Incompatibilities
None.
6.3.
Shelf Life
36 months.
6.4. Special Precautions for Storage
Do not store above 25 °C.
Store in the original package in order to protect from light and moisture.
6.5. Nature and Contents of Container
Polypropylene or polyethylene tablet container containing 100, 500 or 1000 tablets.
Glass container containing 100, 500 or 1000 tablets.
White opaque blister (250pm UPVC) 40gsm UPVDC sealed with 20pm tempered aluminium foil in packes of 28 tablets.
6.6. Instruction for Use/Handling None.
7. Marketing Authorisation Holder
Wockhardt UK Limited
Ash Road North
Wrexham Industrial Estate
Wrexham
LL13 9UF
UK
8. Marketing Authorisation Number
PL 29831/0101
9. Date of First Authorisation/Renewal of Authorisation
10 DATE OF REVISION OF THE TEXT
12/10/2015