GLIBEN

Glibenclamide

Glibenclamide is known as Glyburide in the US and Canada and is sold under the following brand names

U.S. Brand Names: Diabeta; Glynase; Micronase
Foreign Brand Names: Antibet; Apo-Glibenclamide; Azuglucon; Bastiverit; Benclamin; Betanase; Betanese 5; Calabren; Cytagon; D.B.T.; Daonil; Debtan; Diaben; Dibelet; Euglucan; Euglucon; GBN; GBN 5; Gilbesyn; Gilemal; Glamide; Gliban; Gliben; Glibenil; Glibesyn; Glibetic; Glibil; Gliboral; Glidiabet; Glimel; Glimide; Glisulin; Glitisol; Gluben; Glucal; Glucobene; Glucohexal; Glucolon; Glucomid; Glucoven; Glukovital; Glyben; Glycomin; Glynor; Hemi-Daonil; Libanil; Med-Glionil; Melix; Miglucan; Norboral; Orabetic; Pira; Prodiabet; Renabetic; Semi-Daonil; Semi-Euglucon; Sugril; Yuglucon

Presentation

Each uncoated tablet of GLIBEN 5 is white, capsule shaped, imprinted GE/5 one side and G/G the other side. The tablet is 10mm in length and 5mm wide and contains 5mg glibenclamide.

Each uncoated tablet of GLIBEN 2.5 is white, flat, bevel shaped, imprinted GE/2.5 one side and G the other side. The tablet is 6mm in diameter and contains 2.5mg glibenclamide.

Uses

Actions

GLIBEN, an oral hypoglycaemic agent, acts initially on the functioning beta cells of the pancreas to release insulin. Extrapancreatic activity (i.e. improvement in the binding of insulin to tissue insulin receptors and the increase in the number of the receptors themselves) may contribute to the mechanism of action of GLIBEN.

Pharmacokinetics

The pharmacokinetic properties of glibenclamide were investigated in healthy subjects with normal metabolism. Balance studies with ¹⁴C-labelled glibenclamide showed that human subjects absorb the drug almost completely (84 + 9%).

After oral administration of 5mg glibenclamide in man peak serum concentrations are reached at 2 hours; within 24 hours the concentration then falls in keeping with the elimination rate to less than 5% of the maximum level. The elimination half-life from the serum can be divided into a rapid phase (2.1 + 0.7 hours) and a slow phase (10 + 2 hours).

Analysis of the pharmacokinetic findings indicates that cumulation is not to be expected and it was, indeed, not observed even after repeated doses.

Investigations in diabetics showed maximum plasma levels of, approximately, 300ng/mL 2 to 4 hours after administration and, likewise, established that no accumulation occurred even after 15 days' administration.

Glibenclamide is completely metabolised. In the human body its breakdown takes place by hydroxylation of the cyclohexyl group.

Two metabolites have been isolated and identified. The major metabolite M₁ is hydroxylated at the 4-trans-position and another metabolite M₂ is the 3-cis-hydroxy compound. A third metabolite, accounting for only 1.4% of the radioactivity of an oral dose of ¹⁴C-labelled glibenclamide, has been isolated from the urine but not yet identified.

From the fact that the mean metabolism half-life and the mean elimination half-life are closely similar, it may be concluded that the metabolites are not stored in the body and are promptly excreted as soon as they are formed. This conclusion is confirmed by the high renal clearance of the principal metabolite.

The metabolites have practically no hypoglycaemic action.

Indications

GLIBEN is used for treating non-insulin dependent type II diabetes, when diet alone is not adequate.

Dosage and Administration

For primary stabilisation, start with 1 tablet of GLIBEN 2.5 daily before breakfast; if necessary, raise the dose in increments of 1 tablet of GLIBEN 2.5 until the diabetes is controlled. When the daily dosage of GLIBEN 2.5 reaches or exceeds 2 tablets, GLIBEN 5 may be used instead. One tablet of GLIBEN 5 is equivalent to 2 tablets of GLIBEN 2.5. As a rule, the maximum effect is attained with a daily dose of 3 tablets of GLIBEN 5. However, in some cases further improvement in control can be achieved by raising the daily dose from 3 to 4 tablets of GLIBEN 5.

Daily doses of up to 2 tablets of GLIBEN 5 can usually be taken as a single dose before breakfast, but any excess beyond this should be taken before the evening meal. A dose of 4 tablets of GLIBEN 5 should be divided as follows:

2 tablets before breakfast, 1 tablet before lunch and 1 tablet before the evening meal.

Dosage and effectiveness in children has not been established. In debilitated or aged patients, who may be more liable to hypoglycaemia, treatment should be initiated with 1 GLIBEN 2.5 tablet daily.

Contraindications

Insulin dependent type I diabetes (except as adjunctive therapy) severe metabolic decompensation with acidosis, in particular diabetic precoma or coma, serious impairment of renal and hepatic function, hypersensitivity to glibenclamide and pregnancy.

It has yet to be established whether glibenclamide is excreted in breast milk.

However, other sulphonylureas have been found in milk and glibenclamide is, probably, no different in this respect.

Warnings and Precautions

As with other sulphonylurea drugs, GLIBEN is capable of producing severe hypoglycaemia. It may be necessary to institute insulin during illness, stress or surgery.

Adverse Effects

Hypoglycaemia, see Precautions.

Liver dysfunction. Gastrointestinal upsets are exception. Hypersensitivity reactions involve the skin, e.g. purpura, photosensitivity, have been reported. Haemopoietic abnormalities, such as leucopenia or thrombocytopenia, occur in isolated cases.

There have also been occasional instances of haemolytic anaemia. As a rule, such changes are reversible.

Interactions

The hypoglycaemic action of sulphonylureas (including GLIBEN) may be potentiated by certain medicines including NSAID's and others which are highly protein-bound, salicylates, sulphonamides, chloramphenicol, probenecid, coumarins, MAOI's and beta blockers.

The hypoglycaemic action of GLIBEN may be reduced by the concomitant administration of certain medicines including those containing active agents such as acetazolamide, diazoxide, glucagon, thiazide diuretics, nicotinamides, corticosteroids, phenothiazines, thyroid hormones and sympathomimetics.

Overdosage

Overdosage of sulphonylureas including GLIBEN can produce hypoglycaemia.

Pharmaceutical Precautions

Store below 25°C.

Medicine Classification

Prescription Medicine.

Package Quantities

Each bottle of GLIBEN 5 contains 100 x 5mg tablets.

Each bottle of GLIBEN 2.5 contains 100 x 2.5mg tablets.