Antidiabetic Drugs

Posts Tagged ‘Glucotrol’

(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.

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.

There has been little research on the short-term economic benefits of improving glycemic control in patients with NIDDM and therefore, insurance payers are not always willing to underwrite certain lifestyle enhancement programs because they don’t fully understand these benefits. Therefore, a 12-week study was done to determine the amount of money spent on patients given a standard diabetes treatment (5-20mg glipizide GITS [Glucotrol]) or no drug treatment (placebo). Factors such as employee retention, work productivity, absenteeism, bed days, restricted activity days, and frequency of physician visits were compared in these two groups of diabetic patients. 594 patients completed the study.

After 12 weeks, HbA1c and FBG levels were lower in patients treated with glipizide GITS (Gastrointestinal Therapeutic System) than placebo. Improved glycemic control with glipizide GITS [Glucotrol] was associated with higher retention of employed persons and greater productive capacity. Absenteeism increased among those persons only given placebo, but declined slightly for those who received diabetic drug therapy. Patients reporting 1/2 day of work or more per week in bed rose from 4% to 8.4% in the placebo group, but declined from 5.9% to 5.5% for those treated with glipizide GITS (Gastrointestinal Therapeutic System). Bed days and restricted activity days increased for placebo, and decreased for the treated patients.

These differences resulted in higher production losses for patients who were only treated with placebo compared to those given drug treatment. Improved glycemic control with drug therapy also produced a greater decrease in the rate of non-study-related physician visits for patients on glipizide GITS vs. placebo, yielding a direct savings of $11 per patient per month (assuming a cost of $66 per physician visit).

Therefore, improved glycemic control of NIDDM was clearly shown to enhance employment retention and work productivity, and reduced absenteeism, bed days, restricted activity days, and frequency of physician visits. These economic benefits should be considered when performing cost/benefit analyses of diabetes care.