Glucotrol Information
Glucotrol (Glipizide)
Glucotrol (Glipizide) Description
Glucotrol (Glipizide) is an oral blood-glucose-lowering drug of the sulfonylurea class.
The Chemical Abstracts name of glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazine-carboxamido)ethyl]phenyl]sulfonyl]urea. The molecular formula is CHNOS; the molecular weight is 445.55; the structural formula is shown below:
Glipizide is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 NaOH; it is freely soluble in dimethylformamide. Glucotrol (Glipizide) tablets for oral use are available in 5 and 10 mg strengths.
Inert ingredients are: colloidal silicon dioxide; lactose; microcrystalline cellulose; starch; stearic acid.
Glucotrol (Glipizide) Clinical Pharmacology
The primary mode of action of Glucotrol (Glipizide) in experimental animals appears to be the stimulation of insulin secretion from the beta cells of pancreatic islet tissue and is thus dependent on functioning beta cells in the pancreatic islets. In humans, Glucotrol (Glipizide) appears to lower the blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. The mechanism by which Glucotrol (Glipizide) lowers blood glucose during long-term administration has not been clearly established. In man, stimulation of insulin secretion by Glucotrol (Glipizide) in response to a meal is undoubtedly of major importance. Fasting insulin levels are not elevated even on long-term Glucotrol (Glipizide) administration, but the postprandial insulin response continues to be enhanced after at least 6 months of treatment. The insulinotropic response to a meal occurs within 30 minutes after an oral dose of Glucotrol (Glipizide) in diabetic patients, but elevated insulin levels do not persist beyond the time of the meal challenge. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.
Blood sugar control persists in some patients for up to 24 hours after a single dose of Glucotrol (Glipizide) , even though plasma levels have declined to a small fraction of peak levels by that time (see below).
Some patients fail to respond initially, or gradually lose their responsiveness to sulfonylurea drugs, including Glucotrol (Glipizide) . Alternatively, Glucotrol (Glipizide) may be effective in some patients who have not responded or have ceased to respond to other sulfonylureas.
It has been shown that Glucotrol (Glipizide) therapy was effective in controlling blood sugar without deleterious changes in the plasma lipoprotein profiles of patients treated for NIDDM.
In a placebo-controlled, crossover study in normal volunteers, Glucotrol (Glipizide) had no antidiuretic activity and, in fact, led to a slight increase in free water clearance.
Gastrointestinal absorption of Glucotrol (Glipizide) in man is uniform, rapid, and essentially complete. Peak plasma concentrations occur 1–3 hours after a single oral dose. The half-life of elimination ranges from 2–4 hours in normal subjects, whether given intravenously or orally. The metabolic and excretory patterns are similar with the two routes of administration, indicating that first-pass metabolism is not significant. Glucotrol (Glipizide) does not accumulate in plasma on repeated oral administration. Total absorption and disposition of an oral dose was unaffected by food in normal volunteers, but absorption was delayed by about 40 minutes. Thus, Glucotrol (Glipizide) was more effective when administered about 30 minutes before, rather than with, a test meal in diabetic patients. Protein binding was studied in serum from volunteers who received either oral or intravenous Glucotrol (Glipizide) and found to be 98–99% one hour after either route of administration. The apparent volume of distribution of Glucotrol (Glipizide) after intravenous administration was 11 liters, indicative of localization within the extracellular fluid compartment. In mice, no Glucotrol (Glipizide) or metabolites were detectable autoradiographically in the brain or spinal cord of males or females, nor in the fetuses of pregnant females. In another study, however, very small amounts of radioactivity were detected in the fetuses of rats given labelled drug.
The metabolism of Glucotrol (Glipizide) is extensive and occurs mainly in the liver. The primary metabolites are inactive hydroxylation products and polar conjugates and are excreted mainly in the urine. Less than 10% unchanged Glucotrol (Glipizide) is found in the urine.
Glucotrol (Glipizide) Indications And Usage
Glucotrol (Glipizide) is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Glucotrol (Glipizide) Contraindications
Glucotrol (Glipizide) is contraindicated in patients with:
Glucotrol (Glipizide) Precautions
Patients should be informed of the potential risks and advantages of Glucotrol (Glipizide) and of alternative modes of therapy. They should also be informed about the importance of adhering to dietary instructions, of a regular exercise program, and of regular testing of urine and/or blood glucose.
The risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development should be explained to patients and responsible family members. Primary and secondary failure should also be explained.
The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents, some azoles, and other drugs that are highly protein bound, salicylates, sulfonamides, chloramphenicol, probenecid, coumarins, monoamine oxidase inhibitors, and beta adrenergic blocking agents. When such drugs are administered to a patient receiving Glucotrol (Glipizide) , the patient should be observed closely for hypoglycemia. When such drugs are withdrawn from a patient receiving Glucotrol (Glipizide) , the patient should be observed closely for loss of control. binding studies with human serum proteins indicate that Glucotrol (Glipizide) binds differently than tolbutamide and does not interact with salicylate or dicumarol. However, caution must be exercised in extrapolating these findings to the clinical situation and in the use of Glucotrol (Glipizide) with these drugs.
Certain drugs tend to produce hyperglycemia and may lead to loss of control. These drugs include the thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid. When such drugs are administered to a patient receiving Glucotrol (Glipizide) , the patient should be closely observed for loss of control. When such drugs are withdrawn from a patient receiving Glucotrol (Glipizide) , the patient should be observed closely for hypoglycemia.
A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known. The effect of concomitant administration of DIFLUCAN (fluconazole) and Glucotrol (Glipizide) has been demonstrated in a placebo-controlled crossover study in normal volunteers. All subjects received Glucotrol (Glipizide) alone and following treatment with 100 mg of DIFLUCAN as a single daily oral dose for 7 days. The mean percentage increase in the Glucotrol (Glipizide) AUC after fluconazole administration was 56.9% (range: 35 to 81).
Glucotrol (Glipizide) Adverse Reactions
In U.S. and foreign controlled studies, the frequency of serious adverse reactions reported was very low. Of 702 patients, 11.8% reported adverse reactions and in only 1.5% was Glucotrol (Glipizide) discontinued.
The following adverse events have been reported in post-marketing surveillance:
Glucotrol (Glipizide) Overdosage
There is no well documented experience with Glucotrol (Glipizide) overdosage. The acute oral toxicity was extremely low in all species tested (LD greater than 4 g/kg).
Overdosage of sulfonylureas, including Glucotrol (Glipizide) , can produce hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated aggressively with oral glucose and adjustments in drug dosage and/or meal patterns. Close monitoring should continue until the physician is assured that the patient is out of danger. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment occur infrequently, but constitute medical emergencies requiring immediate hospitalization. If hypoglycemic coma is diagnosed or suspected, the patient should be given a rapid intravenous injection of concentrated (50%) glucose solution. This should be followed by a continuous infusion of a more dilute (10%) glucose solution at a rate that will maintain the blood glucose at a level above 100 mg/dL. Patients should be closely monitored for a minimum of 24 to 48 hours since hypoglycemia may recur after apparent clinical recovery. Clearance of Glucotrol (Glipizide) from plasma would be prolonged in persons with liver disease. Because of the extensive protein binding of Glucotrol (Glipizide) , dialysis is unlikely to be of benefit.
Glucotrol (Glipizide) Dosage And Administration
There is no fixed dosage regimen for the management of diabetes mellitus with Glucotrol (Glipizide) or any other hypoglycemic agent. In addition to the usual monitoring of urinary glucose, the patient's blood glucose must also be monitored periodically to determine the minimum effective dose for the patient; to detect primary failure, i.e., inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, i.e., loss of an adequate blood-glucose-lowering response after an initial period of effectiveness. Glycosylated hemoglobin levels may also be of value in monitoring the patient's response to therapy.
Short-term administration of Glucotrol (Glipizide) may be sufficient during periods of transient loss of control in patients usually controlled well on diet.
In general, Glucotrol (Glipizide) should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.
Glucotrol (Glipizide) How Supplied
Glucotrol (Glipizide) tablets are white, dye-free, scored, diamond-shaped, and imprinted as follows:
Glucotrol (Glipizide)
Glucotrol (Glipizide) Principal Display Panel - Mg Tablet Bottle Label
Glucotrol (Glipizide) Principal Display Panel - Mg Tablet Bottle Label
