Glipizide by is a Prescription medication manufactured, distributed, or labeled by NuCare Pharmaceuticals,Inc.. Drug facts, warnings, and ingredients follow.
Tablets: 2.5 mg, 5 mg, 10 mg ( 3).
Most common adverse reactions (incidence > 3%) are dizziness, diarrhea, nervousness, tremor, hypoglycemia and flatulence ( 6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Rising Pharmaceuticals, Inc. at 1-866-562-4597 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Glipizide extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
Glipizide extended-release tablets should be administered orally with breakfast or the first main meal of the day.
The recommended starting dose of glipizide extended-release tablets is 5 mg once daily. Start patients at increased risk for hypoglycemia (e.g. the elderly or patients with hepatic insufficiency) at 2.5 mg [see Use in Specific Population (8.5, 8.6)] .
Dosage adjustment can be made based on the patient’s glycemic control. The maximum recommended dose is 20 mg once daily.
Patients receiving immediate release glipizide may be switched to Glipizide extended-release tablets once daily at the nearest equivalent total daily dose.
When adding glipizide extended-release tablets to other anti-diabetic drugs, initiate glipizide extended-release tablets at 5 mg once daily. Start patients at increased risk for hypoglycemia at a lower dose.
When colesevelam is coadministered with glipizide extended-release tablets, maximum plasma concentration and total exposure to glipizide is reduced. Therefore, glipizide extended-release tablets should be administered at least 4 hours prior to colesevelam.
All sulfonylurea drugs, including glipizide, are capable of producing severe hypoglycaemia [see Adverse Reactions (6)] . Concomitant use of glipizide extended-release tablets with other anti-diabetic medication can increase the risk of hypoglycemia. A lower dose of glipizide extended-release tablets may be required to minimize the risk of hypoglycemia when combining it with other anti-diabetic medications.
Educate patients to recognize and manage hypoglycemia. When initiating and increasing glipizide extended-release tablets in patients who may be predisposed to hypoglycemia (e.g., the elderly, patients with renal impairment, patients on other anti-diabetic medications) start at 2.5 mg. Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic impairment are particularly susceptible to the hypoglycemic action of anti-diabetic medications. Hypoglycemia is also more likely to occur when caloric intake is deficient, after severe or prolonged exercise, or when alcohol is ingested.
The patient’s ability to concentrate and react may be impaired as a result of hypoglycemia. Early warning symptoms of hypoglycemia may be different or less pronounced in patients with autonomic neuropathy, the elderly, and in patients who are taking beta-adrenergic blocking medications or other sympatholytic agents. These situations may result in severe hypoglycemia before the patient is aware of the hypoglycemia.
These impairments may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death.
Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents, including glipizide extended-release tablets, can lead to hemolytic anemia. Avoid use of glipizide extended-release tablets in patients with G6PD deficiency. In post marketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.
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
type 2 diabetes mellitus. The study involved 823 patients who were randomly assigned to one
of four treatment groups.
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.
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glipizide extended-release tablets or any other anti-diabetic drug.
There have been reports of obstructive symptoms in patients with known strictures in association with the ingestion of another drug with this non-dissolvable extended-release formulation. Avoid use of glipizide extended-release tablets in patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic).
The following serious adverse reactions are discussed in more detail below and elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials
of another drug and may not reflect the rates observed in practice.
In clinical trials, 580 patients from 31 to 87 years of age received Glipizide extended-release tablets in doses from 5 mg to 60 mg in both controlled and open trials. The dosages above 20 mg are not recommended dosages. In these trials, approximately 180 patients were treated with glipizide extended-release tablets for at least 6 months.
Table 1 summarizes the incidence of adverse reactions, other than hypoglycemia, that were reported in pooled double-blind, placebo-controlled trials in ≥3% of glipizide extended-release tablets -treated patients and more commonly than in patients who received placebo.
|Glipizide Extended Release
Of the 580 patients that received glipizide extended-release tablets in clinical trials, 3.4% had hypoglycaemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia and 2.6% of patients discontinued for this reason. Hypoglycemia was not reported for any placebo patients.
In clinical trials, the incidence of gastrointestinal (GI) side effects (nausea, vomiting, constipation, dyspepsia), occurred in less than 3% of glipizide extended-release tablets -treated patients and were more common in glipizide extended-release tablets -treated patients than those receiving placebo.
In clinical trials, allergic skin reactions, i.e., urticaria occurred in less than 1.5% of treated patients and were more common in glipizide extended-release tablets treated patients than those receiving placebo. These may be transient and may disappear despite continued use of glipizide XL; if skin reactions persist, the drug should be discontinued.
Laboratory Tests : Mild to moderate elevations of ALT, LDH, alkaline phosphatase, BUN and creatinine have been noted. The relationship of these abnormalities to glipizide is uncertain.
The following adverse reactions have been identified during post approval use of glipizide
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Monitor patients closely for hypoglycemia when glipizide extended-release tablets is coadministered with miconazole. A potential interaction between oral miconazole and oral hypoglycemic agents leading to severe hypoglycemia has been reported [see Clinical Phamacology (12.3)] .
Monitor patients closely for hypoglycemia when glipizide extended-release tablets is coadministered with fluconazole.
Concomitant treatment with fluconazole increases plasma concentrations of glipizide, which may lead to hypoglycemia [see Clinical Phamacology (12.3)] .
Glipizide extended-release tablets should be administered at least 4 hours prior to the administration of colesevelam.
Colesevelam can reduce the maximum plasma concentration and total exposure of glipizide when the two are coadministered [see Clinical Phamacology (12.3)] .
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. There are no adequate and well controlled studies in pregnant women. Glipizide extended-release tablets should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nonteratogenic Effects : Prolonged severe hypoglycemia (4 to 10 days) has been reported in neonates born to mothers who were receiving a sulfonylurea drug at the time of delivery. This has been reported more frequently with the use of agents with prolonged half-lives. If glipizide is used during pregnancy, it should be discontinued at least one month before the expected delivery date.
It is not known whether glipizide extended-release tablets is excreted in human milk. Because the potential for hypoglycemia in nursing infants may exist, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
There were no overall differences in effectiveness or safety between younger and older patients, but greater sensitivity of some individuals cannot be ruled out. Elderly patients are particularly susceptible to the hypoglycemic action of anti-diabetic agents. Hypoglycemia may be difficult to recognize in these patients. Therefore, dosing should be conservative to avoid hypoglycemia. [see Dosage and Administration (2.1), Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)]
There is no information regarding the effects of hepatic impairment on the disposition of glipizide. However, since glipizide is highly protein bound and hepatic biotransformation is the predominant route of elimination, the pharmacokinetics and/or pharmacodynamics of glipizide may be altered in patients with hepatic impairment. If hypoglycemia occurs in such patients, it may be prolonged and appropriate management should be instituted. [see Dosage and Administration (2.1), Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)]
Overdosage of sulfonylureas including glipizide can produce severe hypoglycemia. Mild hypoglycemic symptoms without loss of consciousness or neurologic findings should be treated with oral glucose. Severe hypoglycemic reactions with coma, seizure, or other neurological impairment are medical emergencies requiring immediate treatment. The patient should be treated with glucagon or intravenous glucose. 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 may be prolonged in persons with liver disease. Because of the extensive protein binding of glipizide, dialysis is unlikely to be of benefit.
Glipizide extended-release tablets contain glipizide which is an oral sulfonylurea.
The Chemical Abstracts name of glipizide is 1-cyclohexyl-3-[[p-[2-(5-methylpyrazinecarboxamido) 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:
Glipizide is a whitish, odorless powder with a pKa of 5.9. It is insoluble in water and alcohols, but soluble in 0.1 N NaOH; it is freely soluble in dimethylformamide.
Inert ingredients in the 2.5 mg, 5 mg and 10 mg formulations are: polyethylene oxide, hypromellose, magnesium stearate, sodium chloride, red ferric oxide, cellulose acetate, polyethylene glycol, Opadry ® blue (OY-LS-20921) (hypromellose, lactose monohydrate, titanium dioxide, triacetin and FD&C blue#2) (2.5 mg tablets), Opadry ® white (YS-2-7063) (hypromellose, titanium dioxide and polyethylene glycol) (5 mg and 10 mg tablet) and Opacode ® Black Ink (S-1-277001) (shellac, ferrosoferric oxide, propylene glycol).
System Components and Performance
Glipizide extended-release tablets are similar in appearance to a conventional tablet. It consists, however, of an osmotically active drug core surrounded by a semipermeable membrane. The core itself is divided into two layers: an “active” layer containing the drug, and a “push” layer containing pharmacologically inert (but osmotically active) components. The membrane surrounding the tablet is permeable to water but not to drug or osmotic excipients. As water from the gastrointestinal tract enters the tablet, pressure increases in the osmotic layer and “pushes” against the drug layer, resulting in the release of drug through a small, laser-drilled orifice in the membrane on the drug side of the tablet.
The function of the glipizide extended-release tablets depends upon the existence of an osmotic gradient between the contents of the bi-layer core and fluid in the GI tract. The biologically inert components of the tablet remain intact during GI transit and are eliminated in the feces as an insoluble shell.
Glipizide primarily lowers blood glucose by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Sulfonylureas bind to the sulfonylurea receptor in the pancreatic beta-cell plasma membrane, leading to closure of the ATP-sensitive potassium channel, thereby stimulating the release of insulin.
The insulinotropic response to a meal is enhanced with Glipizide extended-release tablets administration in diabetic patients. The postprandial insulin and C-peptide responses continue to be enhanced after at least 6 months of treatment. In two randomized, double-blind, dose-response studies comprising a total of 347 patients, there was no significant increase in fasting insulin in all Glipizide extended-release tablets -treated patients combined compared to placebo, although minor elevations were observed at some doses.
In studies of glipizide extended-release tablets in subjects with type 2 diabetes mellitus, once daily administration produced reductions in hemoglobin A1c, fasting plasma glucose and postprandial glucose. The relationship between dose and reduction in hemoglobin A1c was not established, however subjects treated with 20 mg had a greater reduction in fasting plasma glucose compared to subjects treated with 5 mg.
The absolute bioavailability of glipizide was 100% after single oral doses in patients with type 2 diabetes mellitus. Beginning 2 to 3 hours after administration of glipizide extended-release tablets, plasma drug concentrations gradually rise reaching maximum concentrations within 6 to 12 hours after dosing. With subsequent once daily dosing of glipizide extended-release tablets, plasma glipizide concentrations are maintained throughout the 24 hour dosing interval with less peak to trough fluctuation than that observed with twice daily dosing of immediate release glipizide.
The mean relative bioavailability of glipizide in 21 males with type 2 diabetes mellitus after administration of 20 mg glipizide extended-release tablets, compared to immediate release glipizide tablets (10 mg given twice daily), was 90% at steady-state. Steady-state plasma concentrations were achieved by at least the fifth day of dosing with glipizide extended-release tablets in 21 males with type 2 diabetes mellitus and patients younger than 65 years. No accumulation of drug was observed in patients with type 2 diabetes mellitus during chronic dosing with glipizide extended-release tablets.
Administration of glipizide extended-release tablets with food has no effect on the 2 to 3 hour lag time in drug absorption. In a single dose, food effect study in 21 healthy male subjects, the administration of glipizide extended-release tablets immediately before a high fat breakfast resulted in a 40% increase in the glipizide mean C max value, which was significant, but the effect on the AUC was not significant. There was no change in glucose response between the fed and fasting state. Markedly reduced GI retention times of the glipizide extended-release tablets over prolonged periods (e.g., short bowel syndrome) may influence the pharmacokinetic profile of the drug and potentially result in lower plasma concentrations.
In a multiple dose study in 26 males with type 2 diabetes mellitus, the pharmacokinetics of glipizide were linear with glipizide extended-release tablets in that the plasma drug concentrations increased proportionately with dose. In a single dose study in 24 healthy subjects, four 5-mg, two 10-mg, and one 20-mg glipizide extended-release tablets were bioequivalent. In a separate single dose study in 36 healthy subjects, four 2.5-mg glipizide extended-release tablets were bioequivalent to one 10-mg glipizide extended-release tablets .
The mean volume of distribution was approximately 10 liters after single intravenous doses in patients with type 2 diabetes mellitus. Glipizide is 98–99% bound to serum proteins, primarily to albumin.
The major metabolites of glipizide are products of aromatic hydroxylation and have no hypoglycemic activity. A minor metabolite, an acetylamino-ethyl benzene derivative, which accounts for less than 2% of a dose, is reported to have 1/10 to 1/3 as much hypoglycemic activity as the parent compound.
Glipizide is eliminated primarily by hepatic biotransformation: less than 10% of a dose is excreted as unchanged drug in urine and feces; approximately 90% of a dose is excreted as biotransformation products in urine (80%) and feces (10%).
The mean total body clearance of glipizide was approximately 3 liters per hour after single intravenous doses in patients with type 2 diabetes mellitus. The mean terminal elimination half-life of glipizide ranged from 2 to 5 hours after single or multiple doses in patients with type 2 diabetes mellitus.
Studies characterizing the pharmacokinetics of glipizide in pediatric patients have not been performed.
There were no differences in the pharmacokinetics of glipizide after single dose administration to older diabetic subjects compared to younger healthy subjects. [see Use in Specific Populations (8.5)]
The pharmacokinetics of glipizide has not been evaluated in patients with varying degree of renal impairment. Limited data indicates that glipizide biotransformation products may remain in circulation for a longer time in subjects with renal impairment than that seen in subjects with normal renal function.
The pharmacokinetics of glipizide has not been evaluated in patients with hepatic impairment.
A potential interaction between oral miconazole and oral glipizide leading to severe hypoglycemia has been reported. Whether this interaction also occurs with the intravenous, topical, or vaginal preparations of miconazole is not known. [see Drug Interactions (7.1)]
Concomitant treatment with fluconazole increases plasma concentrations of glipizide. The effect of concomitant administration of Diflucan ® (fluconazole) and Glipizide Tablets has been demonstrated in placebo controlled crossover study in healthy volunteers. All subjects received Glipizide Tablets alone and following treatment with 100 mg of Diflucan ® as a single daily oral dose for 7 days. The mean percentage increase in the glipizide AUC after fluconazole administration was 56.9% (range: 35 to 81%). [see Drug Interactions (7.2)]
Colesevelam can reduce the maximum plasma concentration and total exposure of glipizide when the two are coadministered. In studies assessing the effect of colesevelam on the pharmacokinetics of glipizide ER in healthy volunteers, reductions in glipizide AUC 0-∞ and C max of 12% and 13%, respectively were observed when colesevelam was coadministered with glipizide ER. When glipizide ER was administered 4 hours prior to colesevelam, there was no significant change in glipizide AUC 0-∞ or C max, -4% and 0%, respectively. [see Drug Interactions (7.3)]
A twenty month study in rats and an eighteen month study in mice at doses up to 75 times the maximum human dose revealed no evidence of drug-related carcinogenicity. Bacterial and in vivo mutagenicity tests were uniformly negative. Studies in rats of both sexes at doses up to 75 times the human dose showed no effects on fertility.
Glipizide extended-release tablets are supplied as 2.5 mg, 5 mg, and 10 mg round, biconvex tablets and imprinted with black ink as follows:
NDC: 68071-4378-3 BOTTLES OF 30
NDC: 68071-4378-6 BOTTLES OF 60
NDC: 68071-4378-9 BOTTLES OF 90
NDC: 68071-4378-2 BOTTLES OF 120
NDC: 68071-4378-8 BOTTLES OF 180
Recommended Storage: The tablets should be protected from moisture and humidity. Store at 20° to 25°C (68° to 77º F); [see USP Controlled Room Temperature].
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Inform patients of the potential adverse reactions of glipizide extended-release tablets including hypoglycemia. Explain the risks of hypoglycemia, its symptoms and treatment, and conditions that predispose to its development to patients and responsible family members. Also inform patients about the importance of adhering to dietary instructions, of a regular exercise program, and of regular testing of glycemic control.
Inform patients that glipizide extended-release tablets should be swallowed whole. Inform patients that they should not chew, divide or crush tablets and they may occasionally notice in their stool something that looks like a tablet. In the glipizide extended-release tablets, the medication is contained within a non-dissolvable shell that has been specially designed to slowly release the drug so the body can absorb it.
Advise patients with diabetes to inform their healthcare provider if they are pregnant, contemplating pregnancy, breastfeeding, or contemplating breastfeeding.
Trademarks are the property of their respective owners.
Rising Pharmaceuticals, Inc.
Allendale, NJ 07401
Unique Pharmaceutical Laboratories
(A Div. of J. B. Chemicals & Pharmaceuticals Ltd.),
Mumbai 400 030, India
Glipizide Extended-Release Tablets (GLIP i zide)
What are Glipizide Extended-Release Tablets?
It is not known if glipizide extended-release tablet is safe and effective in children under 18 years of age.
Who Should Not Take Glipizide Extended-Release Tablets?
Do not use glipizide extended-release tablets if you:
What should I tell my doctor before taking Glipizide Extended-Release Tablets?
Before you take Glipizide Extended-Release Tablets, tell your healthcare provider if you:
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
Glipizide extended-release tablets may affect the way other medicines work, and other medicines may affect how glipizide extended-release tablets work. Some medicines can affect how well glipizide extended-release tablet works or may affect your blood sugar level.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.
How should I take Glipizide Extended-Release Tablets?
What should I avoid while taking Glipizide Extended-Release Tablets?
What are the possible side effects of Glipizide Extended-Release Tablets?
Glipizide extended-release tablet can cause serious side effects, including:
If you have signs or symptoms of low blood sugar, eat or drink something with sugar in it right away. If you do not feel better or your blood sugar level does not go up, call your healthcare provider or go to the nearest emergency room.
The most common side effects of glipizide extended-release tablet include: dizziness, diarrhea, nervousness, tremor, and gas.
These are not all the possible side effects of Glipizide Extended-Release Tablets. For more information, ask your healthcare provider or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How to store Glipizide Extended-Release Tablets?
Keep glipizide extended-release tablets and all medicines out of reach of children.
General information about the safe and effective use of Glipizide Extended -Release Tablets.
Medicines are sometimes prescribed for purposes other than those listed in a patient information leaflet. Do not use glipizide extended-release tablets for a condition for which it was not prescribed. Do not give glipizide extended-release tablets to other people, even if they have the same symptoms you have. It may harm them.
This Patient Information summarizes the most important information about glipizide extended-release tablets. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about glipizide extended-release tablets that is written for healthcare professionals.
For more information about glipizide extended-release tablets please call 1-(866)-562-4597
What are the ingredients in Glipizide Extended-Release Tablets?
Active ingredient: glipizide
Inactive ingredients: polyethylene oxide, hypromellose, magnesium stearate, sodium chloride, red ferric oxide, cellulose acetate, polyethylene glycol, Opadry ® blue (OY-LS-20921) (hypromellose, lactose monohydrate, titanium dioxide, triacetin and FD&C blue#2) (2.5 mg tablets) Opadry ® white (YS-2-7063) (hypromellose, titanium dioxide and polyethylene glycol) (5 mg and 10 mg tablet) Opacode ® Black Ink (S-1-277001) (shellac, ferrosoferric oxide, propylene glycol)
Rising Pharmaceuticals, Inc.
Allendale, NJ 07401
Unique Pharmaceutical Laboratories
(A Div. of J. B. Chemicals & Pharmaceuticals Ltd.),
Mumbai 400 030, India
glipizide tablet, film coated, extended release
|Labeler - NuCare Pharmaceuticals,Inc. (010632300)|