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Glibenclamide, 5 mg tablets

Drug formTablets

ATC categoryEndocrinology

ATC subcategoryOral hypoglycemic agents

Brand nameGlibenclamide

Generic nameGlibenclamide

Composition

Each tablet of Glibenclamide 5 mg contains:

active ingredient: glibenclamide – 5 mg;

excipients: microcrystalline cellulose, calcium phosphate dibasic, ethylcellulose, magnesium stearate, talc purified.

Pharmacological group and ATC code
Sulfonylurea antidiabetic; A10BB01.

Chemical name and CAS number
1-{4-[2-(5-Chloro-2-methoxybenzamido)ethyl]benzenesulphonyl}-3-cyclohexylurea; 10238-21-8.

Pharmacology

Glibenclamide is second-generation oral sulfonylurea hypoglycemic agents.

Like other sulfonylurea antidiabetic agents, Glibenclamide lowers blood glucose concentration in diabetic and nondiabetic individuals. The mechanism of action is based on pancreatic and extra-pancreatic effects. Drugs reduce blood glucose concentration principally by stimulating secretion of endogenous insulin from the beta cells of the pancreas. At the same time, the drag reduces the excitability threshold and thereby improves the ability of beta cells to respond to the physiological glucose stimulation. Extrapancreatic effect is based on enhancement of peripheral sensitivity of insulin at postreceptor (probably intracellular) site(s). Following short-term administration of Glibenclamide, an increase in insulin binding has been demonstrated in monocytes obtained from healthy individuals, but not in adipocytes obtained from diabetic patients. Like other sulfonylureas, Glibenclamide alone is ineffective in the absence of functioning beta cells.

The mechanism(s) of action of Glibenclamide during prolonged administration has not been fully established. Glibenclamide-induced improvement in glucose tolerance during long-term therapy persists despite a gradual decline in glucose- or meal-stimulated secretion of endogenous insulin towards pretreatment levels. During prolonged administration of sulfonylureas, including, extrapancreatic effects appear to substantially contribute to the hypoglycemic action of the drugs. Many extrapancreatic effects of the drugs have been proposed and/or studied, but the principal effects appear to include enhanced peripheral sensitivity to insulin and reduction of basal hepatic glucose production; however, the nature of the long-term hypoglycemic effect and the mechanism(s) involved remain to be fully elucidated. There is evidence that Glibenclamide enhances the peripheral action of insulin at postreceptor (probably intracellular) site(s) and reduces basal hepatic glucose production during long-term administration. An increase in insulin binding and/or number of insulin receptors has also been demonstrated in monocytes and adipocytes obtained from diabetic patients receiving long-term therapy with the drug.

Pharmacokinetics

Glibenclamide is readily absorbed from the gastrointestinal tract, peak plasma concentrations usually occurring within 2 to 4 hours, and is extensively bound to plasma proteins. Absorption may be slower in hyperglycaemic patients and may differ according to the particle size of the preparation used. It is metabolised, almost completely, in the liver, the principal metabolite being only very weakly active. Approximately 50% of a dose is excreted in the urine and 50% via the bile into the faeces. The elimination half-life of glibenclamide is about 10 hours (5-26 hours)

Uses
Non insulin dependent (type 2 diabetes mellitus), whenever blood glucose levels cannot be controlled adequately by diet.
Dosage and administration

The dosing is determined individually depending on the age, severity of diabetes, prandial glycemia levels and 2 hours after meals.

The usual initial dose in type 2 diabetes mellitus is 2.5 to 5 mg (1/2 -1 tab) daily with breakfast, if nececcery adjusted every 7 days by increments of 2.5 or 5 mg (1/2 -1 tab) daily up to achieve compensation parameters of carbohydrate metabolism. Maintenance dosage is 5 to 10 mg (1-2 tablets) per day. The maximum daily dose: 15 mg (3 tablets), in exceptional cases: 20 mg (4 tablets). Daily doses up to 10 mg usually to be taken 1 time / day, in the morning, before eating.

Doses greater than 10 mg daily shold be taken in the morning and the rest of the dose – in the evening.Tablets should be taken whole, without chewing, with a small amount of liquid.

Because of the relatively long duration of action of glibenclamide, it is best avoided in the elderly.

Adverse effects

Gastrointestinal disturbances, rare, depending on dose may occur nausea, vomiting, heartburn, anorexia, diarrhoea, and a metallic taste in mouth ; increased appetite and weight gain may occur.Skin rashes and pruritus may occur and photosensitivity has been reported.

Hypoglycaemia may occur; severe hypoglycaemia is usually an indication of overdosage and an inadequate diet. Hypoglycaemia is more likely with glibenclamide, which have been associated with severe, prolonged, and sometimes fatal hypoglycaemia.

Other severe effects may be manifestations of a hypersensitivity reaction. They include the elevated liver enzymes activity, hepatitis and cholestatic jaundice, leucopenia, thrombocytopenia, aplastic anaemia, agranulocytosis, erythema multiforme, the Stevens-Johnson syndrome, exfoliative dermatitis, and erythema nodosum.

Glibenclamide is stated to have mild diuretic actions (occasionally induce a syndrome of inappropriate secretion of antidiuretic hormone (SIADH) characterised by water retention, hyponatraemia, and CNS effects).

Precautions

Caution must be exercised when prescribing the drug to patients with infectious diseases, as well as in cases of serious operations, injuries (in such situations may require a translation of the patient to insulin). During the selection of the dose when changing drugs or irregular use of glibenclamide decreases the reaction rate, and therefore is not recommended for patients to engage in potentially hazardous activities. Be wary appoint glibenclamide in patients with cerebral atherosclerosis, dementia, and patients who abuse alcohol. Potential risk of hypoglycemia should be borne in mind when assigning glibenclamide simultaneously dicoumarol, MAO inhibitors, sulfonamides, phenylbutazone, chloramphenicol, cyclophosphamide, salicylates, beta-blockers.

Beta blockers, clonidine, guanethidine and reserpinehave, been reported both to increase hypoglycaemia and to mask the typical sympathetic warning signs.Should be careful in the appointment of glibenclamide patients with a history of allergic reactions to the instructions on the sulfonamide drugs, as there may be cross-allergy. Glibenclamide should be taken regularly and, if possible, in the same time of day. Patients should be warned about the need for careful adherence to regimen of the drug.Patient should be warned about the possibility of slowing down the speed of psychomotor reactions at the beginning of treatment with glibenclamide.This phenomenon disappears when the normalization of carbohydrate metabolism.

Patients taking glibenclamide should abstain from alcohol. In the case of alcohol consumption may develop disulfiram reactions and severe hypoglycemia. In the treatment of glibenclamide must regularly monitor blood glucose and daily excretion of glucose in the urine.

Use in pediatrics: The efficacy and safety of Glibenclamide has not been investigated in paediatric patients. Glibenclamideshould therefore not be used in children.

Contraindications
  • Type 1 diabetes mellitus,
  • type 2 diabetes mellitus in patients with ketoacidosis,precoma, diabetic coma,
  • hypersensitivity to sulfonamides,
  • expressed liver and kidneys dysfunctions,
  • pregnancy, breast-feeding.
  • Overdosage

    Symptoms: hypoglycemia (feeling of intense hunger, sweating, palpitations and tremors in the body, anxiety, headaches, sleep disorders, depressed mood, irritability, lack of movement, speech and vision disorders, loss of consciousness).

    Treatment: in mild cases – intake of sugar or easily digestible carbohydrates, and in severe cases – intravenous injection of glucose solution 40% 40-80 ml, and then 5-10% glucose solution infusion. Maybe intramuscular or subcutaneous injection of 1-2 mg of glucagon.

    Drug interactions

    Increased risk of hepatotoxicity when Glibenclamide given with bosentan —avoid concomitant use.

    An increased hypoglycaemic effect has occurred or might be expected with ACE inhibitors, alcohol, allopurinol, some analgesics (notably azapropazone, phenylbutazone, and the salicylates), azole antifungals (fluconazole, ketoconazole, and miconazole), chloramphenicol, cimetidine, clofibrate and related compounds, coumarin anticoagulants, fluoroquinolones, heparin, MAOIs, octreotide (although this may also produce hyperglycaemia), ranitidine, sulfinpyrazone, sulfonamides (including co-trimoxazole), tetracyclines, and tricyclic antidepressants, ciprofloxacin, norfloxacin.

    A diminished hypoglycaemic effect, possibly requiring an increased dose of sulfonylurea, has been seen or might be expected on theoretical grounds with adrenaline, aminoglutethimide, chlorpromazine, corticosteroids, diazoxide, oral contraceptives, rifamycins, thiazide diuretics, and thyroid hormones.

    Beta blockers, clonidine, guanethidine and reserpinehave, been reported both to increase hypoglycaemia and to mask the typical sympathetic warning signs.

    Identification

    White or off white scored cylindrical tablets with a few small darker spots.

    Presentation

    Cardboard box containing 48 tablets: 2 blister with 24 tablets.

    Expiry date

    3 years. Do not use after the expiration date.

    Prescription status

    To be dispensed with prescription.

    Storage conditions

    Store in dry place, out of the reach of children at temperature not higher than 15ºC. Protect from light.