Glipizide Tablet
FDA Label NDC 72888-231

Full FDA labeling including Indications, Dosage, Usage, and Precautions

Structured Product Label

The following Structured Product Label (SPL) was submitted to the FDA by Advagen Pharma Limited for the product Glipizide (NDC 72888-231). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.

This specific version of the label includes detailed information regarding description, pharmacokinetics:, indications and usage, contraindications, special warning on increased risk of cardiovascular mortality, laboratory tests, information for patients, pregnancy:, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.

Label Section Quick Index

→ Description

→ Pharmacokinetics:

→ Indications And Usage

→ Contraindications

→ Special Warning On Increased Risk Of Cardiovascular Mortality

→ Laboratory Tests

→ Information For Patients

→ Pregnancy:

→ Adverse Reactions

→ Overdosage

→ Dosage And Administration

→ How Supplied

→ Recommended Storage:

→ Package Label-principal Display Panel

Description

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 C ₂₁H ₂₇N ₅O ₄S; the molecular weight is 445.55; the structural formula is shown below:

Chemical Structure (Glipizide Tabs Usp Structure)

Glipizide is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 NNaOH; it is freely soluble in dimethylformamide. Glipizide tablets for oral use are available in 2.5 mg, 5mg and 10 mg strengths.

Inactive ingredients are: colloidal silicon dioxide; croscarmellose sodium, lactose anhydrous; microcrystalline cellulose and stearic acid.

Meets USP Dissolution test 2.

Pharmacokinetics:

Gastrointestinal absorption of 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. 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, 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 glipizide and found to be 98–99% one hour after either route of administration. The apparent volume of distribution of glipizide after intravenous administration was 11 liters, indicative of localization within the extracellular fluid compartment. In mice, no 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 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 glipizide is found in the urine.

Indications And Usage

Glipizide tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Contraindications

Glipizide tablets are contraindicated in patients with:

Known hypersensitivity to the drug.
Type 1 diabetes mellitus, diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.

Special Warning On Increased Risk Of Cardiovascular Mortality

The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to one of four treatment groups ( Diabetes, 19, supp. 2: 747–830, 1970).

UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy.

Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure.

Laboratory Tests

Blood and urine glucose should be monitored periodically. Measurement of glycosylated hemoglobin may be useful.

Information For Patients

Patients should be informed of the potential risks and advantages of 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.

Physician Counseling Information for Patients
In initiating treatment for type 2 diabetes, diet should be emphasized as the primary form of treatment. Caloric restriction and weight loss are essential in the obese diabetic patient. Proper dietary management alone may be effective in controlling the blood glucose and symptoms of hyperglycemia. The importance of regular physical activity should also be stressed, and cardiovascular risk factors should be identified and corrective measures taken where possible. Use of glipizide or other antidiabetic medications must be viewed by both the physician and patient as a treatment in addition to diet and not as a substitution or as a convenient mechanism for avoiding dietary restraint. Furthermore, loss of blood glucose control on diet alone may be transient, thus requiring only short-term administration of glipizide tablets or other antidiabetic medications. Maintenance or discontinuation of glipizide tablets or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.

Pregnancy:

Glipizide was found to be mildly fetotoxic in rat reproductive studies at all dose levels (5–50 mg/kg). This fetotoxicity has been similarly noted with other sulfonylureas, such as tolbutamide and tolazamide. The effect is perinatal and believed to be directly related to the pharmacologic (hypoglycemic) action of glipizide. In studies in rats and rabbits, no teratogenic effects were found. There are no adequate and well controlled studies in pregnant women. Glipizide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Because recent information suggests that abnormal blood glucose levels during pregnancy are associated with a higher incidence of congenital abnormalities, many experts recommend that insulin be used during pregnancy to maintain blood glucose levels as close to normal as possible.

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 glipizide discontinued.

Overdosage

There is no well documented experience with glipizide overdosage. The acute oral toxicity was extremely low in all species tested (LD ₅₀greater than 4 g/kg).

Overdosage of sulfonylureas, including 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 glipizide from plasma would be prolonged in persons with liver disease. Because of the extensive protein binding of glipizide, dialysis is unlikely to be of benefit.

Dosage And Administration

There is no fixed dosage regimen for the management of diabetes mellitus with 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 glipizide tablets may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

In general, glipizide tablets should be given approximately 30 minutes before a meal to achieve the greatest reduction in postprandial hyperglycemia.

How Supplied

Glipizide tablets 2.5 mg are round, white to off-white, uncoated tablets, debossed I1 on one side and Ʌ on other side. They are supplied as follows:

NDC 72888-115-30, bottles of 30.

NDC 72888-115-01, bottles of 100.

NDC 72888-115-05, bottles of 500.

NDC 72888-115-00, bottles of 1000.

Glipizide tablets 5 mg are Round, white to off-white, uncoated tablets, debossed Λ on one side and break line on other side. They are supplied as follows:
I2

NDC 72888-116-30, bottles of 30.

NDC 72888-116-01, bottles of 100.

NDC 72888-116-05, bottles of 500.

NDC 72888-116-00, bottles of 1000.

Glipizide tablets 10 mg are Round, white to off-white, uncoated tablets, debossed Λ on one side and break line on other side. They are supplied as follows:
I4

NDC 72888-117-30, bottles of 30.

NDC 72888-117-01, bottles of 100.

NDC 72888-117-05, bottles of 500.

NDC 72888-117-00, bottles of 1000.