Glibenclamide

Drug Approvals

(British Approved Name, rINN)

International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish): Glibenclamida; Glibenclamidum; Glibenklamid; Glibenklamidas; Glibenklamidi; Glybenclamide; Glybenzcyclamide; Glyburide (US-AN); HB-419; U-26452

C₂₃H₂₈CIN₃0₅S = 494.0.

CAS — 10238-21-8.

ATC — A10BB01.

Note. The name glibornuride has frequently but erroneously been applied to glibenclamide.

Pharmacopoeias. In China, Europe, International, Japan, and US.

European Pharmacopoeia, 6th ed. (Glibenclamide). A white or almost white, crystalline powder. Practically insoluble in water slightly soluble in alcohol and in methyl alcohol sparingly soluble in dichloromethane.

The United States Pharmacopeia 31, 2008 (Glyburide). Store in airtight containers.

Adverse Effects, Treatment, and Precautions

As for sulfonylureas in general.

For a suggestion that the failure rate in type 2 diabetics treated with glibenclamide may be higher than that for those treated with chlorpropamide, see Diabetes Mellitus under Uses and Administration of Chlorpropamide.

Hypoglycaemia. Severe hypoglycaemia may occur in any patient given any sulfonylurea glibenclamide which has a relatively prolonged duration of action, may cause severe hypoglycaemia more often than shorter-acting sulfonylureas. In a 1983 review of 57 instances of hypoglycaemia associated with glibenclamide the median age of patients affected was 70 years only one was less than 60 years old. Median daily dosage was 10 mg. Coma or disturbed consciousness was seen in 46 patients. Ten of these remained comatose despite alleviation of their hypoglycaemia and died up to 20 days after presentation. The authors noted that, including their series of 57 cases, there had been published reports on 101 cases of severe hypoglycaemia with glibenclamide, 14 with a fatal outcome. There has been a report of hypoglycaemic coma associated with the inhalation of glibenclamide by a worker at a pharmaceutical plant.

Porphyria. Glibenclamide has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.

Interactions

As for sulfonylureas in general.

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 hyper-glycaemic 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. About 50% of a dose is excreted in the urine and 50% via the bile into the faeces.

Uses and Administration

Glibenclamide is a sulfonylurea antidiabetic. It is given orally in the treatment of type 2 diabetes mellitus and has a duration of action of up to 24 hours.

The usual initial dose of conventional formulations in type 2 diabetes mellitus is 2.5 to 5 mg daily with breakfast, adjusted every 7 days in steps of 2.5 or 5 mg daily up to 15 mg daily. Although increasing the dose above 15 mg is unlikely to produce further benefit, doses of up to 20 mg daily have been given. Doses greater than 10 mg daily may be given in 2 divided doses. Because of the relatively long duration of action of glibenclamide, it is best avoided in the elderly. In some countries micronised preparations of glibenclamide are available, in which the drug is formulated with a smaller particle size, and which have enhanced bioavailability. The usual initial dose of one such preparation (Glynase PresTab; Pharmacia Upjohn, USA) is 1.5 to 3 mg daily, adjusted every 7 days in steps of 1.5 mg, up to a usual maximum of 12 mg daily. Doses greater than 6 mg daily may be given in 2 divided doses.

Action. Proceedings of a symposium on the mechanism of action of glibenclamide.

EFFECTS ON THE HEART. A reduced incidence of ventricular fibrillation has been reported in diabetics treated with glibenclamide who develop myocardial infarction, compared with those receiving other treatments or with nondiabetic patients with myocardial infarction. However, some evidence has also suggested that sulfonylureas may impair the adaptive responses of the heart to ischaemia.

Preparations

British Pharmacopoeia 2008: Glibenclamide Tablets

The United States Pharmacopeia 31, 2008: Glyburide and Metformin Hydrochloride Tablets Glyburide Tablet.

Proprietary Preparations

Argentina: Agobilina Benclamid Daonil Diabe Pass Diabemin Euglucon Gardoton Glentor Glibediab † Glibemida Glidanil Gliptid Glitral GON Pira Siruc

Australia: Daonil Glimel Semi-Daonil

Austria: Daonil Dia-Eptal Euglucon Gilemal Glucobene Glucostad Normoglucon Semi-Euglucon

Belgium: Bevoren Daonil Euglucon

Brazil: Aglucil Benclamin Clamiben Daonil Diaben Diabetty’s † Diabexil Euglucon Gliben † Glibenclamon Glibendiab Glibexil † Glicamin Glionil Lisaglucon Uni Gliben †

Canada: DiaBeta Euglucon Gen-Glybe

Chile: Daonil Euglusid Mezalit

Czech Republic: Betan-ase † Glibenhexal † Glucobene Humedia † Maninil

Denmark: Daonil Hexaglucon Regulin †

Finland: Daonil † Euglamin Euglucon Origlucon Semi-Euglucon

France: Daonil Euglucan Hemi-Daonil Miglucan

Germany: Azuglucon † Bastiverit † duraglucon N Euglucon N Glib Glib-ratiopharm Gliben Glib-en-Azu † Gliben-Puren N † Glibenbeta Glibendoc Glibenhexal Glimidstada † Glucoremed † Glukoreduct † Glukovital glycolande N † Humedia Jutaglucon † Maninil Praeciglucon † Semi-Euglucon N

Greece: Daonil Deroctyl Diabefar †

Hong Kong: Calabren † Clamide Daonil Euglucon Gliben Gliboral Glimel Glitisol Marglucon Semi-Daonil † Semi-Euglucon Xeltic

Hungary: Gilemal Glucobene Maninil

India: Daonil Euglucon Glinil Glybovin Semi-Daonil Semi-Euglucon

Indonesia: Condiabet Daonil Glidanil Glimel Gluconic Glulo Glyamid Libronil Prodiabet Prodiamel Renabetic Semi-Daonil Tiabet Trodeb

Ireland: Daonil Semi-Daonil

Israel: Daonil † Glibetic Gluben

Italy: Daonil Euglucon Gliben Gliboral

Japan: Euglucon

Malaysia: Claben † Daonil Debtan † Dibelet Gliben Glibesyn Glimide

Mexico: Abuglib Apogly Biostin Daonil Dibetid Diglexol Euglucon Gadinor Glemicid Glibenil Glibenval Glicavin Glicoxem Glifarcal Glihexal Glikeyer † Glipar Glucal Glucoven Insusym Mibeclag Nadib † Norboral Ocrix Reglusan

The Netherlands: Daonil Hemi-Daonil †

Norway: Daonil †

New Zealand: Gliben

Philippines: Ameciadin Daonil Diabitor Euglucon Eundin Gluban Glymod Insol Loduice Orabetic Semi-Euglucon Sentionyi Sucron

Poland: Euclamin

Portugal: Daonil Euglucon Semi-Daonil Semi-Euglucon †

Russia: Betanase Glibamide Glibex Glidanil Maninil

South Africa: Daonil Diacare Euglucon † Glycomin

Singapore: Clamide Daonil Dibelet GBN † Glibemid † Glibesyn Glimel Glimide

Spain: Daonil Euglucon Glucolon Norglicem

Sweden: Daonil Euglucon

Switzerland: Daonil Euglucon Glibasan Glibenorme Glibesifar Melix Semi-Daonil Semi-Euglucon †

Thailand: Benclamin BNIL Cytagon † Daonil Daono Debtan Diabenol Dibelet Diclanil Euglucon Glencamide † Gliben † Glibetic Glibic Gluconil Gluzo Locose Manoglucon Med-Glionil † Semi-Euglucon † Sugril Unil Xeltic

Turkey: Dianorm Diyalen Gliben

United Arab Emirates: Glynase Mini-Glynase

UK: Daonil Diabetamide † Euglucon † Semi-Daonil †

USA: DiaBeta Glynase Micronase

Venezuela: Daonil Euglucon Gliciron.

Multi-ingredient

Argentina: DBI Duo Glucovance Isloglib Medobis G Metformin Duo

Australia: Glucovance

Belgium: Glucovance

Brazil: Glucovance

Chile: Bi-Euglucon M Diaglitab Plus Glifortex-G Glimet Glucovance Glukaut Hipoglucin DA

Czech Republic: Glibomet Glucovance

France: Glucovance

Greece: Daopar † Normell

Hong Kong: Glucovance

India: Diaforte Glinil M

Indonesia: Glucovance

Italy: Bi-Euglucon M Bi-Euglucon † Gliben  † Glibomet Gliconorm Glicorest Gliformin Glucomide Suguan M Suguan †

Malaysia: Glucovance

Mexico: Apometglu Bi-Dizalon Bi-Euglucon M Bi-Pradia Duo-Anglucid Glinorboral Glucotec Glucovance Imalet Insusym-Forte Maviglin Midapharma Mifelar-C Nadib-M Norfaben M Sibet-C Sil-Norboral Wadil

The Netherlands: Glucovance

Philippines: Euglo Plus Glucovance

Portugal: Glucovance

Russia: Glibomet Glucovance

South Africa: Glucovance

Singapore: Glucovance

Switzerland: Glucovance

USA: Diofen Glucovance Glybofen

Venezuela: Bi-Euglucon Diaformina Plus Glucovance.