Posts Tagged ‘Diabeta’
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.
Current Oral Antidiabetic Therapy: Sulfonylureas
These agents are derivatives of sulfonic acid and urea, and produce their effects by binding to receptors on the surface of pancreatic beta cells. The binding of sulfonylureas results in depolarization of the cell membrane, the influx of calcium ions, and subsequent release of insulin. The sulfonylureas were developed in 1954 and continue to be the most widely prescribed oral agents for the treatment of type 2 diabetes. Early evidence of associated increased cardiovascular morbidity has not been reproduced, and today sulfonylureas are considered relatively safe agents that have proven effective over long-term use.
Sulfonylureas: First-Generation
Sulfonylureas consists of two groups or generations of agents. The first-generation agents are now less commonly used because second-generation agents are as effective and have fewer side effects. Two first-generation agents, chlorpropamide and tolbutamide are still popular with some physicians. This group also contains tolazamide and acetohexa-mide; both are rarely used today.
Chlorpropamide. Brand Name Drug: Diabinese. Chlorpropamide is administered once daily in a 100 mg or 250 mg tablet. Its half-life is extremely long, with effects lasting up to >48 hours. The principal disadvantage of this agent is that it is excreted almost entirely renally. Therefore, the risk of hypoglycemia makes this drug relatively contraindicated in the elderly and absolutely contraindicated in those with renal insufficiency. Chlorpropamide also enhances the effects of vasopressin, at times resulting in the syndrome of inappropriate antidiuretic hormone (SIADH). With the introduction of more potent agents that have a much shorter half-life and fewer side effects, today there is little reason to use chlorpropamide.
Tolbutamide. Brand Name Drug: Orinase. Tolbutamide has a much shorter duration of action (6-10 hours) and is metabolized primarily by the liver. It is a safer agent than chlorpropamide; however, it is relatively weak in its antidiabetic activity.
Sulfonylureas: Second-Generation
Second-generation sulfonylureas are the most commonly prescribed agents for treating type 2 diabetes. As a group, they are at least 100 times more potent than tolbutamide. They include glyburide, glipizide, and the newest agent, glimepiride. Glyburide and glipizide, when used as monotherapy, have proven effective in lowering HgbA1C 1% to 2% in most studies.
Glyburide. Brand Names: Diabeta, Glycron, Glynase, Micronase. Glyburide is metabolized in the liver to metabolites with reduced hypoglycemic activity. These metabolites are then excreted renally. Therefore, in the elderly and patients with compromised renal function, glyburide is relatively contraindicated because of the risk of hypoglycemia. Even in normal subjects it is not unusual to see persistence of glyburide’s effects for up to 24 hours. In the United Kingdom Prospective Diabetes Study (UKPDS), a multicenter trial of >5000 patients with type 2 diabetes mellitus, the incidence of hypoglycemia with glyburide was similar to that seen with chlorpropamide. Patients usually are started on a 2.5-mg or 5-mg tablet in the morning before the first meal of the day. The dose can be escalated gradually to a maximum of 20 mg/day. However, it is rare to see further improvement in efficacy with doses > 10 mg/day. Again, this agent should be used with caution in the elderly population and in those with renal insufficiency.
There also is a micronized form of glyburide. However, it has been difficult to find exactly equivalent dosages between the two forms, which can lead to confusion for the patient and physician. The micronized agents have not been shown to have a higher bio availability or greater efficacy than regular glyburide.
Glipizide. Brand Name Drug: Glucotrol. Glipizide is completely metabolized in the liver and excreted primarily by the kidneys. However, it is not as potent as glyburide at raising basal insulin levels and therefore is the preferred sulfonylurea in elderly patients or those with renal insufficiency. It usually is started with 5 mg orally 30 minutes prior to breakfast. If the dose exceeds 15 mg/day, then it is best to divide the doses by giving it before breakfast and before dinner. The maximum recommended dose is 40 mg/day, although it is rare to see additional efficacy with doses >20 mg/day. There is also an extended release form of glipizide, which allows for once a day dosing.
Glimepiride. Brand Name Drug: Amaryl. In 1996, a new sulfonylurea, glimepiride, was approved for use in the treatment of type 2 diabetes. It is the most potent of the sulfonylureas to date, requiring a 1-, 2-, or 4-mg dose once daily. It is completely metabolized in the liver, making it safe in the elderly and in those with renal insufficiency. The maximal recommended dose is 6 mg/day, and this agent is of equal efficacy whether given once or twice daily. Like the other sulfonylureas, glimepiride acts as an insulin secretagogue, but in comparative trials, it caused fewer episodes of hypoglycemia. Other data from comparative trials show that glimepiride provides greater postprandial insulin secretion, but fasting glucose control and HgbA1C lowering is similar to that of glyburide. Glimepiride has been shown to have extrapancreat-ic in vitro effects on glucose uptake, but the clinical significance of these effects is still to be determined.