Category Archive: Drugs
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Glipizide
(British Approved Name, US Adopted Name, rINN)
Drug Nomenclature
International Nonproprietary Names (INNs) in main languages (French, Latin, Russian, and Spanish):
Pharmacopoeias. In China, Europe, and US.
European Pharmacopoeia, 6th ed. (Glipizide). A white or almost white crystalline powder. Practically insoluble in water and in alcohol very slightly soluble in acetone and in dichloromethane. It dissolves in dilute solutions of alkali hydroxides.
The United States Pharmacopeia 31, 2008 (Glipizide). Store in airtight containers. Protect from light.
Adverse Effects, Treatment, and Precautions
As for sulfonylureas in general.
Porphyria. Glipizide has been associated with acute attacks of porphyria and is considered unsafe in porphyric patients.
Interactions
As for sulfonylureas in general.
Antacids. Magnesium hydroxide and sodium bicarbonate have been reported to increase the rate of absorption, although not the total amount absorbed, of a dose of glipizide in healthy subjects. No such effect was seen with aluminium hydroxide
Pharmacokinetics
Glipizide is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 1 to 3 hours after a single dose. It is extensively bound to plasma proteins and has a half-life of about 2 to 4 hours. It is metabolised mainly in the liver and excreted chiefly in the urine, largely as inactive metabolites.
Uses and Administration
Glipizide 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 is 2.5 to 5 mg daily given as a single dose about 30 minutes before breakfast. Dosage may be adjusted at intervals of several days by amounts of 2.5 to 5 mg daily, to a maximum of 20 mg daily. Doses up to 40 mg daily have been used, but see below. Doses larger than 15 mg daily are given in two divided doses before meals. Modified-release formulations of glipizide are available in some countries one such preparation (Glucotrol XL Pfizer, USA) is given in doses of 5 to 10 mg daily as a single dose with breakfast.
Administration. Although glipizide may be given in doses up to a maximum of 40 mg daily, evidence for the benefits of high doses is scanty. A small study in patients with type 2 diabetes mellitus found that not only did increases in glipizide doses to more than 10 mg daily produce little or no benefit, but that the higher doses were associated with reduced rises in plasma-insulin concentrations and a lesser reduction in plasma-glucose concentrations. There is, however, some evidence that glycae-mic control and insulin sensitivity can be improved by the use of a modified-release rather than a conventional formulation of glipizide.
Preparations
British Pharmacopoeia 2008: Glipizide Tablets
The United States Pharmacopeia 31, 2008: Glipizide and Metformin Hydrochloride Tablets Glipizide Tablets.
Proprietary Preparations
Argentina: Minodiab
Australia: Melizide Minidiab
Austria: Glibenese Minidiab
Belgium: Glibenese Minidiab
Brazil: Minidiab
Chile: Minidiab Xiprine
Czech Republic: Antidiabf Glucotrol † Mediab Minidiab
Denmark: Glibenese Minidiab
Finland: Apamid † Glibenese Melizid Minidiab
France: Glibenese Minidiab Ozidia
Greece: Glibenese Minodiab
Hong Kong: Diase Glucotrol Minidiab Sunglucon
Hungary: Minidiab
India: Diaglip Glez Glide Glucolip Glynase Glyzip
Indonesia: Aldiab Glucotrol Glyzid
Ireland: Glibenese
Israel: Gluco-Rite
Italy: Minidiab
Malaysia: Dibizicle † Dipazide Glix Melizide Minidiab
Mexico: Glupitel Luditec Minodiab Pigloss Singloben
The Netherlands: Glibenesej
Norway: Apamid Minidiab
New Zealand: Glipid Minidiab
Philippines: Glix Minidiab
Poland: Antidiab Glibenese
Portugal: Minidiab
Russia: Glibenese Minidiab †
South Africa: Minidiab
Singapore Beapizide Diactin Diasef Melizide Minidiab
Spain: Glibenese Minodiab
Sweden: Apamid † Glipiscandl Minidiab
Switzerland: Glibenese
Thailand: Apamid † Depizide Diase Dipazide Gipzide Glipimed Glizide Glucodiab Glygen GP-Zide Melizide Minibit Minidiab Namedia Pezide
Turkey: Glucotrol Minidiab
UK: Glibenese Minodiab
USA: Glucotrol
Venezuela: Minidiab.
Multi-ingredient
India: Diaglip M Metaglez
USA: Metaglip.
Glimepiride
Drug Approvals
(British Approved Name, US Adopted Name, rINN)
INNs in other languages (French, Latin, and Spanish):
Pharmacopoeias. In Europe and US.
European Pharmacopoeia, 6th ed. (Glimepiride). A white to almost white powder. It exhibits polymorphism. Practically insoluble in water slightly soluble in dichloromethane soluble in dimethylformamide very slightly soluble in methyl alcohol.
The United States Pharmacopeia 31, 2008 (Glimepiride). A white to almost white powder. Practically insoluble in water sparingly soluble in dichloromethane soluble in dimethylformamide slightly soluble in methyl alcohol. It dissolves in dilute alkali hydroxides and in dilute acids. Store at a temperature not exceeding 25°.
Adverse Effects, Treatment, and Precautions
As for sulfonylureas in general. In some countries hepatic and haematological monitoring is recommended in patients receiving glimepiride in the UK the BNF considers the practical value of such monitoring unproven.
Fasting. Glimepiride, given in unchanged doses but with the time of the single daily dose switched from morning to just before breaking fast after sunset, was used in Muslim patients during Ramadan without causing an increased incidence of hypoglycaemic episodes.
For further advice on the management of diabetes mellitus in fasting Muslim patients during Ramadan see under Precautions of Insulin.
Interactions
As for sulfonylureas in general.
Pharmacokinetics
Glimepiride is completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur in 2 to 3 hours, and it is highly protein bound. The drug is extensively metabolised to two main metabolites, a hydroxy derivative and a carboxy derivative. The half-life after multiple doses is about 9 hours. About 60% of a dose is eliminated in the urine and 40% in the faeces.
Uses and Administration
Glimepiride is a sulfonylurea antidiabetic. It is given orally for the treatment of type 2 diabetes mellitus. Initial doses of 1 to 2 mg daily may be increased if necessary to 4 mg daily for maintenance. The maximum recommended dose is 6 mg in the UK and 8 mg in the USA.
Preparations
The United States Pharmacopeia 31, 2008: Glimepiride Tablets.
Proprietary Preparations
Argentina: Adiuvan Amaryl Endial Glemaz Gluceride Glucopirida Islopir Lomet Next Step
Australia: Amaryl Aylide Diapride Dimirel
Austria: Amaryl
Belgium: Amarylle
Brazil: Amaryl Azulix Bioglic Diamellitis Glimepibal Glimepil Glimeprid † Glimeran Glimesec † Hipomeril
Canada: Amaryl
Chile: Amaryl Glemaz Glucomet
Czech Republic: Amarwin Amaryl Amyx Apo-Glimep Eglymad Glemid GlimTek Glymexan Melyd Metis Oltar
Denmark: Amaryl
Finland: Amaryl
France: Amarel
Germany: Amaryl Glimegamma Glimerid
Greece: Dialosa Glimepiron Glimespes Glimexin Gliperin Mepirid Penoza Pharlecon Saccharofar Solosa Sucryl Tipo II Toremol
Hong Kong: Amaryl Diapride
Hungary: Amaryl Dialosa Glempid GlimeWin Gl
India Gliprex Limeral Meglimid Melyd Sintecal
India: Amaryl Betaglim Diaglim Euglim Glimcip Glimiprex Glimitab Glimulin Glyree Glyree M Karmelitos
Indonesia: Amadiab Amaryl Anpiride Glamarol Glimexal Gluvas Mapryl Metrix Relide
Ireland: Amaryl
Israel: Amaryl
Italy: Amaryl Solosa
Malaysia: Amaryl Diapride Glimaryl Glimin Glimulin Miaryl
Mexico: Amaryl Glupropan Zukedib
The Netherlands: Amaryl
Norway: Amaryl
New Zealand: Amaryl
Philippines: Imerid Norizec Solosa
Poland: Amaryl Amyx Avaron Betaglid Diaril Glemid Glibetic Glibezid Glidiamid Glimehexal Glimesan Glipid Limeral Melyd Oltar Pemidal Symglic
Portugal: Amaryl Diapiride Glimial Gludon
Russia: Amaryl Glemaz
South Africa: Amaryl Glamaryl
Singapore: Amaryl Diapride
Spain: Amaryl Roname
Sweden: Amaryl
Switzerland: Amaryl
Thailand: Amaryl
Turkey: Amaryl Diameprid Glimax
UK: Amaryl Niddaryl
USA: Amaryl
Venezuela: Amaryl Dimavyl Glimerid.
Multi-ingredient
Czech Republic: Avaglim Tandemact
France: Avaglim Tandemact
Greece: Avaglim
Hungary: Avaglim
India: Betaglim Mf Exermet GM Glimiprex M † Glimulin-MF †
Indonesia: Avandaryl
Portugal: Avaglim Tandemact
USA: Avandaryl Duetact.
Gliclazide
Drug Approvals
(British Approved Name, rINN)
International Nonproprietary Names (INNs) in main languages (French, Latin, and Spanish):
Pharmacopoeias. In China, and Europe.
European Pharmacopoeia, 6th ed. (Gliclazide). A white or almost white powder. Practically insoluble in water slightly soluble in alcohol sparingly soluble in acetone freely soluble in dichloromethane.
Adverse Effects, Treatment, and Precautions
As for sulfonylureas in general. The BNF suggests that gliclazide may be suitable for use in patients with renal impairment, but that careful monitoring of blood-glucose concentration is essential. UK licensed product information recommends that it should not be used in patients with severe renal impairment.
Interactions
As for sulfonylureas in general.
Pharmacokinetics
Gliclazide is readily absorbed from the gastrointestinal tract. It is extensively bound to plasma proteins. The half-life is about 10 to 12 hours. Gliclazide is extensively metabolised in the liver to metabolites that have no significant hypoglycaemic activity. Metabolites and a small amount of unchanged drug are excreted in the urine.
Uses and Administration
Gliclazide is a sulfonylurea antidiabetic. It is given orally in the treatment of type 2 diabetes mellitus and has a duration of action of 12 to 24 hours. Because its effects are less prolonged than those of chlorpropamide or glibenclamide it may be more suitable for elderly patients, who are prone to hypoglycaemia with longer-acting sulfonylureas. The usual initial dose is 40 to 80 mg daily, gradually increased, if necessary, up to 320 mg daily. Doses of more than 160 mg daily are given in 2 divided doses. A modified-release tablet is also available: the usual initial dose is 30 mg once daily, increased if necessary up to a maximum of 120 mg daily.
Preparations
British Pharmacopoeia 2008: Gliclazide Tablets.
Proprietary Preparations
Argentina: Aglucide Diamicron Unava
Australia: Diamicron Glyade Nidem Oziclide
Austria: Diamicron
Belgium: Diamicron Uni Diamicron
Brazil: Azukon Diamicron Glicaron
Canada: Diamicron
Chile: Dianormax
Czech Republic: Diabrezide Diaprel
Denmark: Diamicron
France: Diamicron
Germany: Diamicron
Greece: Diamicron
Hong Kong: CP-Gliz Diamicron Diamitex Dianorm Glimicron Glucozide Glupozide Glyzyl Licla Marclazide Nidem Qualizide Suclear Sun-Glizide
Hungary: Diaprel Gluctam
India: Diamicron Gliza Glizid Glycigon Glycinorm Glygard Lycazid Semi-Glycigon
Indonesia: Diamicron Fredam Glicab Glidabet Glucodex Glucored Glukolos Glycafor Linodiab Meltika Nufamicron Pedab Tiaglib Xepabet Zumadiac
Ireland: Diabrezide Diaclide Diamicron
Italy: Cronemet Diabrezide Diamicron Dramion Galtes Glucobloc
Malaysia: Diacron † Diamicron Dianid Glimicron Glucozide Glyade Medoclazide Melicron † Opglucon Reclide Sun-Glizide
Mexico: Diamicron
The Netherlands: Diamicron
New Zealand: Diamicron Glizon
Philippines: Clibite Glizid Diaclid Diamicron Dianorm Glubitor Gluconil Glucoprime
Poland: Diabezidum Diabrezide Diaprel Diazidan Glazide Glinormax Norsulin
Portugal: Diamicron
South Africa: Diaglucide Diamicron Glucomed Glycron Glygard Ziclin
Singapore: Diamicron Dianorm Glimicron Glizide Glucozide Medoclazide Melicron †
Spain: Diamicron Uni Diamicron
Switzerland: Diamicron
Thailand: Cadicon Diabeside Diaclaron † Diamaze † Diamexon Diamicron Dianid Glicron Glucocron Glucozide Glycon Medoclazide Serviclazide
Turkey: Betanorm Diamicron Glazid Glumikron Oramikron
United Arab Emirates: Glyzide
UK: Diaglyk Diamicron
Venezuela: Diamicron Glidan Reclide †
Multi-ingredient:
India: Exermet GZ Gliclamet Glizid-M Glycigon-M Glycinorm M Glygard M Glyroz.
Acetohexamide
Drug Approvals
(British Approved Name, US Adopted Name, rINN)
Pharmacopoeias. InJapan and US.
The United States Pharmacopeia 31, 2008 (Acetohexamide). A white, practically odourless, crystalline powder. Practically insoluble in water and in ether soluble 1 in 230 of alcohol and 1 in 210 of chloroform soluble in py-ridine and in dilute solutions of alkali hydroxides.
Profile
Acetohexamide is a sulfonylurea antidiabetic. Its duration of action is 12 hours or more. It has been given orally in the treatment of type 2 diabetes mellitus in a usual initial dose of 250 mg daily before breakfast. The daily dose may then be increased by 250 to 500 mg at intervals of 5 to 7 days, to a maintenance dose of up to 1.5 g daily increasing the dose above 1.5 g does not usually lead to further benefit. Doses in excess of 1 g daily may be taken in 2 divided doses, before the morning and evening meals.
Preparations
The United States Pharmacopeia 31, 2008: Acetohexamide Tablets.
Proprietary Preparations
Canada: Dimelor;
Hong Kong: Dimelor;
Italy: Dimelor;
South Africa: Dimelor;
Spain: Gamadiabet;
United Kingdom: Dimelor;
United States: Dymelor
Nateglinide
Drug Approvals
(US Adopted Name, rINN)
INNs in other languages:
Adverse Effects and Precautions
As for Repaglinide.
Overdosage. A blood-glucose concentration of 2.0 mmol/litre was measured 1 hour after ingestion of nateglinide 3.42 g in a 30-year-old woman. She was able to walk unaided, but seemed drowsy. The hypoglycaemic effect of nateglinide lasted for 6 hours and was treated with intravenous glucose (total dose 100 g).
Renal impairment. A single-dose pharmacokinetic studyfound that moderate to severe renal impairment (creatinine clearance 15 to 50 mL/minute per 1.73 m) and haemodialysis did not significantly affect the pharmacokinetics of nateglinide. However, the metabolite Ml has been found to accumulate in patients with renal impairment requiring haemodialysis after repeated doses of nateglinide, but it may be removed by haemodialysis. M1 is a maj or metabolite that has modest hypoglycaemic activity compared with nateglinide. An analysis of pooled study data found that efficacy and tolerability of nateglinide in elderly diabetic patients were not significantly affected by renal impairment (mean creatinine clearance 50.9 mL/minute per 1.73 m). Nevertheless, a 56-year-old diabetic woman whose renal failure was managed with haemodialysis experienced severe hypoglycaemia with nateglinide the reaction was attributed to the accumulation of M1 Licensed product information in the UK and USA suggest that no dosage adjustment is necessary in renal impairment, although UK information suggests that dose adjustment might be required in patients on haemodialysis.
Interactions
As with other oral antidiabetics, the efficacy of nateglinide may be affected by drugs independently increasing or decreasing blood glucose concentrations (see Sulfonylureas).
Antibacterials. In a study of healthy subjects, rifampicin reduced the plasma concentrations and half-life of nateglinide, probably by induction of its metabolism by the cytochrome P450 isoenzyme CYP2C9. The glucose-lowering effect of nateglinide was not affected, but there was a marked interindividual variation in the pharmacokinetic changes, and the authors suggested that some diabetic patients could be affected.
Antifungals. In a study of healthy subjects, fluconazole raised the plasma concentrations and prolonged the half-life of nateglinide, probably by inhibition of its metabolism by the cytochrome P450 isoenzyme CYP2C9. The glucose-lowering effect of nateglinide was not affected, but a low dose of nateglinide had been used and the authors suggested that in diabetic patients fluconazole may enhance and prolong the effects of nateglinide.
Lipid regulating drugs. A study investigating the effects of the gemfibrozil and itraconazole combination on the pharmacokinetics of nateglinide showed only a limited interaction. Nateglinide plasma concentrations were raised moderately and the blood glucose response to nateglinide was not significantly changed. This is in contrast to the substantial interaction of gemfibrozil with repaglinide.
Pharmacokinetics
Nateglinide is rapidly absorbed after oral doses, with peak plasma concentrations occurring within one hour and an absolute bioavailability of 73%. Nateglinide is 98% bound to plasma proteins. It is mainly metabolised by cytochrome P450 isoenzyme CYP2C9, and to a lesser extent by CYP3A4. Major metabolites include Ml which is less potent than nateglinide. The parent drug and metabolites are mainly excreted in the urine but about 10% is eliminated in the faeces. The elimination half-life is about 1.5 hours.
Uses and Administration
Nateglinide, like repaglinide, is a meglitinide antidiabetic used in the treatment of type 2 diabetes mellitus. It is given within the 30 minutes before meals in oral doses of 60 or 120 mg three times daily. This may be increased to 180 mg three times daily if necessary. Nateglinide is also given in similar doses with metformin or a thiazolidinedione in type 2 diabetes not adequately controlled by these drugs alone. Although dose adjustment is not generally required in renal impairment, hypoglycaemia has been attributed to accumulation of the metabolite M1 (see above).
Preparations
Proprietary Preparations
Argentina: Nateglin Starlix
Brazil: Starlix
Canada: Starlix
Chile: Gluconol Starlix
Czech Republic: Starlix Trazec
Denmark: Starlix †
Finland: Starlix
Germany: Starlix
Greece: Starlix
Hong Kong: Starlix!
Hungary: Starlix
India: Glinate
Indonesia: Starlix
Ireland: Starlix
Japan: Starsis
Malaysia: Starlix
Mexico: Starlix
The Netherlands: Starlix Trazec
Norway: Starlix
New Zealand: Starlix †
Philippines: Starlix
Portugal: Starlix Trazec
Russia: Starlix
South Africa: Starlix
Singapore: Starlix
Spain: Starlix
Sweden: Starlix
Switzerland: Starlix
Turkey: Starlix
UK: Starlix
USA: Starlix
Multi-ingredient
Brazil: Starform
Venezuela: Starform