Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 22 February 2017


INDICATIONS & USAGE Glipizide extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

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Advisory information

CONTRAINDICATIONS Glipizide extended-release tablets are contraindicated in patients with: Known hypersensitivity to glipizide or any excipients in the tablets. Type 1 diabetes mellitus, diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
Special warnings and precautions

PRECAUTIONS Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glipizide extended-release tablets or any other anti-diabetic drug.

Renal and Hepatic Disease: The pharmacokinetics and/or pharmacodynamics of glipizide may be affected in patients with impaired renal or hepatic function.

If hypoglycemia should occur in such patients, it may be prolonged and appropriate management should be instituted.

GI Disease: Markedly reduced GI retention times of the glipizide extended-release tablets may influence the pharmacokinetic profile and hence the clinical efficacy of the drug.

Hypoglycemia: All sulfonylurea drugs are capable of producing severe hypoglycemia.

Proper patient selection, dosage, and instructions are important to avoid hypoglycemic episodes.

Renal or hepatic insufficiency may affect the disposition of glipizide and the latter may also diminish gluconeogenic capacity, both of which increase the risk of serious hypoglycemic reactions.

Elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency are particularly susceptible to the hypoglycemic action of glucose-lowering drugs.

Hypoglycemia may be difficult to recognize in the elderly, and in people who are taking beta-adrenergic blocking drugs.

Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when alcohol is ingested, or when more than one glucose-lowering drug is used.

Therapy with a combination of glucose-lowering agents may increase the potential for hypoglycemia.

Loss of Control of Blood Glucose: When a patient stabilized on any diabetic regimen is exposed to stress such as fever, trauma, infection, or surgery, a loss of control may occur.

At such times, it may be necessary to discontinue glipizide and administer insulin.

The effectiveness of any oral hypoglycemic drug, including glipizide, in lowering blood glucose to a desired level decreases in many patients over a period of time, which may be due to progression of the severity of the diabetes or to diminished responsiveness to the drug.

This phenomenon is known as secondary failure, to distinguish it from primary failure in which the drug is ineffective in an individual patient when first given.

Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.

Hemolytic Anemia: Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents can lead to hemolytic anemia.

Because glipizide belongs to the class of sulfonylurea agents, caution should be used in patients with G6PD deficiency and a non-sulfonylurea alternative should be considered.

In postmarketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency.

Blood and urine glucose should be monitored periodically.

Measurement of hemoglobin A1C may be useful.

Patients should be informed that glipizide extended-release tablets should be swallowed whole.

Patients should not chew, divide or crush tablets.

Patients should be informed of the potential risks and advantages of glipizide extended-release tablets 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 also should be explained.

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 extended-release tablets 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 extended-release tablets or other antidiabetic medications.

Maintenance or discontinuation of glipizide extended-release tablets or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.

The hypoglycemic action of sulfonylureas may be potentiated by certain drugs including nonsteroidal anti-inflammatory agents 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 glipizide, the patient should be observed closely for hypoglycemia.

When such drugs are withdrawn from a patient receiving glipizide, the patient should be observed closely for loss of control.

In vitro binding studies with human serum proteins indicate that 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 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 glipizide, the patient should be closely observed for loss of control.

When such drugs are withdrawn from a patient receiving 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 fluconazole and glipizide has been demonstrated in a placebo-controlled crossover study in normal volunteers.

All subjects received glipizide alone and following treatment with 100 mg of fluconazole 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 %).

In studies assessing the effect of colesevelam on the pharmacokinetics of glipizide ER in healthy volunteers, reductions in glipizide

AUC0-? and Cmax 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 AUC0-? or Cmax, - 4 % and 0 %, respectively.

Therefore, glipizide ER should be administered at least 4 hours prior to colesevelam to ensure that colesevelam does not reduce the absorption of glipizide.

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 was found to be mildly fetotoxic in rat reproductive studies at all dose levels (5 to 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.

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.

Although it is not known whether glipizide is excreted in human milk, some sulfonylurea drugs are known to be 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.

If the drug is discontinued and if diet alone is inadequate for controlling blood glucose, insulin therapy should be considered.

Safety and effectiveness in children have not been established.

Of the total number of patients in clinical studies of glipizide extended-release tablets, 33 percent were 65 and over.

Approximately 1 to 2 days longer were required to reach steady-state in the elderly.

(See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION .)There were no overall differences in effectiveness or safety between younger and older patients, but greater sensitivity of some individuals can not be ruled out.

As such, it should be noted that elderly, debilitated or malnourished patients, and those with adrenal or pituitary insufficiency, are particularly susceptible to the hypoglycemic action of glucose-lowering drugs.

Hypoglycemia may be difficult to recognize in the elderly.

In addition, in elderly, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions.

Adverse reactions

ADVERSE REACTIONS In U.S. controlled studies the frequency of serious adverse experiences reported was very low and causal relationship has not been established.

The 580 patients from 31 to 87 years of age who received glipizide extended-release tablets in doses from 5 mg to 60 mg in both controlled and open trials were included in the evaluation of adverse experiences.

All adverse experiences reported were tabulated independently of their possible causal relation to medication.

Hypoglycemia: See PRECAUTIONS and OVERDOSAGE sections.

Only 3.4 % of patients receiving glipizide extended-release tablets had hypoglycemia documented by a blood-glucose measurement <60 mg/dL and/or symptoms believed to be associated with hypoglycemia.

In a comparative efficacy study of glipizide extended-release tablets and glipizide tablets, hypoglycemia occurred rarely with an incidence of less than 1 % with both drugs.

In double-blind, placebo-controlled studies the adverse experiences reported with an incidence of 3 % or more in glipizide extended-release tablet-treated patients include: Glipizide ER (%) Placebo (%) Adverse Effect (N= 278) (N=69) Asthenia 10.1 13.0 Headache 8.6 8.7 Dizziness 6.8 5.8 Nervousness 3.6 2.9 Tremor 3.6 0.0 Diarrhea 5.4 0.0 Flatulence 3.2 1.4 The following adverse experiences occurred with an incidence of less than 3 % in glipizide extended-release tablet-treated patients: Body as a whole-pain Nervous system-insomnia, paresthesia, anxiety, depression and hypesthesia Gastrointestinal-nausea, dyspepsia, constipation and vomiting Metabolic-hypoglycemia Musculoskeletal-arthralgia

leg cramps and myalgia Cardiovascular-syncope Skin-sweating and pruritus Respiratory-rhinitis Special senses-blurred vision Urogenital-polyuria Other adverse experiences occurred with an incidence of less than 1 % in glipizide extended-release tablet-treated patients: Body as a whole-chills Nervous system-hypertonia, confusion, vertigo, somnolence, gait abnormality and decreased libido Gastrointestinal-anorexia and trace blood in stool Metabolic-thirst and edema Cardiovascular-arrhythmia, migraine, flushing and hypertension Skin-rash and urticaria Respiratory-pharyngitis and dyspnea Special senses-pain in the eye, conjunctivitis and retinal hemorrhage Urogenital-dysuria Although these adverse experiences occurred in patients treated with glipizide extended-release tablets

a causal relationship to the medication has not been established in all cases.

There have been rare reports of gastrointestinal irritation and gastrointestinal bleeding with use of another drug in this non-deformable sustained release formulation, although causal relationship to the drug is uncertain.

Postmarketing Experience The following adverse events have been reported in postmarketing surveillance: Gastrointestinal: abdominal pain Hepatobiliary: Cholestatic and hepatocellular forms of liver injury accompanied by jaundice have been reported rarely in association with glipizide; glipizide extended-release tablets should be discontinued if this occurs.

The following are adverse experiences reported with immediate release glipizide and other sulfonylureas, but have not been observed with glipizide extended-release tablets: Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see PRECAUTIONS), aplastic anemia and pancytopenia have been reported with sulfonylureas.

Metabolic: Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas.

In the mouse, glipizide pretreatment did not cause an accumulation of acetaldehyde after ethanol administration.

Clinical experience to date has shown that glipizide has an extremely low incidence of disulfiram-like alcohol reactions.

Endocrine Reactions: Cases of hyponatremia and the syndrome of inappropriate antidiuretic hormone (SIADH) secretion have been reported with glipizide and other sulfonylureas.

Laboratory Tests: The pattern of laboratory test abnormalities observed with glipizide was similar to that for other sulfonylureas.

Occasional mild to moderate elevations of SGOT, LDH, alkaline phosphatase, BUN and creatinine were noted.

One case of jaundice was reported.

The relationship of these abnormalities to glipizide is uncertain, and they have rarely been associated with clinical symptoms.

Usage information

Dosing and administration

DOSAGE & ADMINISTRATION There is no fixed dosage regimen for the management of diabetes mellitus with glipizide extended-release tablets or any other hypoglycemic agent.

Glycemic control should be monitored with hemoglobin A1C and/or blood-glucose levels 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.

Home blood-glucose monitoring may also provide useful information to the patient and physician.

Short-term administration of glipizide extended-release tablets may be sufficient during periods of transient loss of control in patients usually controlled on diet.

In general, glipizide extended-release tablets should be given with breakfast.

Recommended Dosing: The usual starting dose of glipizide extended-release tablets as initial therapy is 5 mg per day, given with breakfast.

Those patients who may be more sensitive to hypoglycemic drugs may be started at a lower dose.

Dosage adjustment should be based on laboratory measures of glycemic control.

While fasting blood-glucose levels generally reach steady-state following initiation or change in glipizide extended-release tablet dosage, a single fasting glucose determination may not accurately reflect the response to therapy.

In most cases, hemoglobin A1C level measured at three month intervals is the preferred means of monitoring response to therapy.

Hemoglobin A1C should be measured as glipizide extended-release tablet therapy is initiated and repeated approximately three months later.

If the result of this test suggests that glycemic control over the preceding three months was inadequate, the glipizide extended-release tablet dose may be increased.

Subsequent dosage adjustments should be made on the basis of hemoglobin A1C levels measured at three month intervals.

If no improvement is seen after three months of therapy with a higher dose, the previous dose should be resumed.

Decisions which utilize fasting blood glucose to adjust glipizide extended-release tablet therapy should be based on at least two or more similar, consecutive values obtained seven days or more after the previous dose adjustment.

Most patients will be controlled with 5 mg to 10 mg taken once daily.

However, some patients may require up to the maximum recommended daily dose of 20 mg.

While the glycemic control of selected patients may improve with doses which exceed 10 mg, clinical studies conducted to date have not demonstrated an additional group average reduction of hemoglobin A1C beyond what was achieved with the 10 mg dose.

Based on the results of a randomized crossover study, patients receiving immediate release glipizide may be switched safely to glipizide extended-release tablets once-a-day at the nearest equivalent total daily dose.

Patients receiving immediate release glipizide also may be titrated to the appropriate dose of glipizide extended-release tablets starting with 5 mg once daily.

The decision to switch to the nearest equivalent dose or to titrate should be based on clinical judgment.

In elderly patients, debilitated or malnourished patients, and patients with impaired renal or hepatic function, the initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see PRECAUTIONS section).

Combination Use: When adding other blood-glucose-lowering agents to glipizide extended-release tablets for combination therapy, the agent should be initiated at the lowest recommended dose, and patients should be observed carefully for hypoglycemia.

Refer to the product information supplied with the oral agent for additional information.

When adding glipizide extended-release tablets to other blood-glucose-lowering agents, glipizide extended-release tablets can be initiated at 5 mg.

Those patients who may be more sensitive to hypoglycemic drugs may be started at a lower dose.

Titration should be based on clinical judgment.

When colesevelam is coadministered with glipizide ER, maximum plasma concentration and total exposure to glipizide is reduced.

Therefore, glipizide ER should be administered at least 4 hours prior to colesevelam.

Patients Receiving Insulin: As with other sulfonylurea-class hypoglycemics, many patients with stable type 2 diabetes receiving insulin may be transferred safely to treatment with glipizide extended-release tablets.

When transferring patients from insulin to glipizide extended-release tablets, the following general guidelines should be considered: For patients whose daily insulin requirement is 20 units or less, insulin may be discontinued and glipizide extended-release tablet therapy may begin at usual dosages.

Several days should elapse between titration steps.

For patients whose daily insulin requirement is greater than 20 units, the insulin dose should be reduced by 50 % and glipizide extended-release tablet therapy may begin at usual dosages.

Subsequent reductions in insulin dosage should depend on individual patient response.

Several days should elapse between titration steps.

During the insulin withdrawal period, the patient should test urine samples for sugar and ketone bodies at least three times daily.

Patients should be instructed to contact the prescriber immediately if these tests are abnormal.

In some cases, especially when the patient has been receiving greater than 40 units of insulin daily, it may be advisable to consider hospitalization during the transition period.

Patients Receiving Other Oral Hypoglycemic Agents: As with other sulfonylurea-class hypoglycemics, no transition period is necessary when transferring patients to glipizide extended-release tablets.

Patients should be observed carefully (1 to 2 weeks) for hypoglycemia when being transferred from longer half-life sulfonylureas (e.g., chlorpropamide) to glipizide extended-release tablets due to potential overlapping of drug effect.

More information

Category Value
Authorisation number ANDA076467
Agency product number X7WDT95N5C
Orphan designation No
Product NDC 52125-764
Date Last Revised 12-11-2015
RXCUI 310489
Marketing authorisation holder REMEDYREPACK INC.