Glyburide Tablets, USP, (nonmicronized), Rx only

DESCRIPTION

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displayName: Description Section
FDA Article Code: 34089-3

Glyburide is an oral blood-glucose-lowering drug of the sulfonylurea class. Glyburide USP is a white, crystalline compound, formulated as glyburide tablets of 1.25, 2.5, and 5 mg strengths for oral administration. Inactive ingredients: dibasic calcium phosphate dihydrate, magnesium stearate, microcrystalline cellulose, sodium alginate, and talc. The chemical name for glyburide is 1-[[p-[2-(5-chloro-o-anisamido)-ethyl]phenyl]-sulfonyl]-3-cyclohexylurea and the molecular weight is 493.99. The structural formula is represented below.

CLINICAL PHARMACOLOGY

id: 9cf20fc5-1c30-4254-9bdb-ebb33f947482
displayName: Clinical Pharmacology Section
FDA Article Code: 34090-1

Actions
 
Glyburide 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 glyburide lowers blood glucose during long-term administration has not been clearly established. With chronic administration in Type II diabetic patients, the blood glucose lowering effect persists despite a gradual decline in the insulin secretory response to the drug. Extrapancreatic effects may be involved in the mechanism of action of oral sulfonylurea hypoglycemic drugs. The combination of glyburide and metformin may have a synergistic effect, since both agents act to improve glucose tolerance by different but complementary mechanisms.

Some patients who are initially responsive to oral hypoglycemic drugs, including glyburide, may become unresponsive or poorly responsive over time. Alternatively, glyburide tablets may be effective in some patients who have become unresponsive to one or more other sulfonylurea drugs.

In addition to its blood glucose lowering actions, glyburide produces a mild diuresis by enhancement of renal free water clearance. Disulfiram-like reactions have very rarely been reported in patients treated with glyburide tablets.

INDICATIONS AND USAGE

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displayName: Indications & Usage Section
FDA Article Code: 34067-9

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

CONTRAINDICATIONS

id: 72db1b25-0a42-4d35-9342-eefe041f739b
displayName: Contraindications Section
FDA Article Code: 34070-3

Glyburide tablets are contraindicated in patients with: Known hypersensitivity or allergy to the drug.
Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
Type I diabetes mellitus.
Concomitant administration of bosentan.

SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY

id: 07517357-e87e-4b70-b122-905e18ca897e
displayName: Warnings Section
FDA Article Code: 34071-1

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.

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
glyburide
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.

PRECAUTIONS

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displayName: Precautions Section
FDA Article Code: 42232-9

Bioavailability studies have demonstrated that micronized glyburide tablets 3 mg provide serum glyburide concentrations that are not bioequivalent to those from nonmicronized glyburide tablets 5 mg.  Therefore, patients should be retitrated when transferred from micronized glyburide tablets or other oral hypoglycemic agents.

ADVERSE REACTIONS

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displayName: Adverse Reactions Section
FDA Article Code: 34084-4

Hypoglycemia

See
PRECAUTIONS
and
OVERDOSAGE
Sections.

Gastrointestinal Reactions

Cholestatic jaundice and hepatitis may occur rarely which may progress to liver failure; glyburide tablets should be discontinued if this occurs.

Liver function abnormalities, including isolated transaminase elevations, have been reported.

Gastrointestinal disturbances, e.g., nausea, epigastric fullness, and heartburn are the most common reactions, having occurred in 1.8% of treated patients during clinical trials. They tend to be dose related and may disappear when dosage is reduced.

Dermatologic Reactions

Allergic skin reactions, e.g., pruritus, erythema, urticaria, and morbilliform or maculopapular eruptions occurred in 1.5% of treated patients during clinical trials. These may be transient and may disappear despite continued use of glyburide; if skin reactions persist, the drug should be discontinued.

Porphyria cutanea tarda and photosensitivity reactions have been reported with sulfonylureas.

Hematologic Reactions

Leukopenia, agranulocytosis, thrombocytopenia, hemolytic anemia (see
PRECAUTIONS
), aplastic anemia, and pancytopenia have been reported with sulfonylureas.

Metabolic Reactions

Hepatic porphyria and disulfiram-like reactions have been reported with sulfonylureas; however, hepatic porphyria has not been reported with glyburide and disulfiram-like reactions have been reported very rarely.

Cases of hyponatremia have been reported with glyburide and all other sulfonylureas, most often in patients who are on other medications or have medical conditions known to cause hyponatremia or increase release of antidiuretic hormone. The syndrome of inappropriate antidiuretic hormone (SIADH) secretion has been reported with certain other sulfonylureas, and it has been suggested that these sulfonylureas may augment the peripheral (antidiuretic) action of ADH and/or increase release of ADH.

Other Reactions

Changes in accommodation and/or blurred vision have been reported with glyburide and other sulfonylureas. These are thought to be related to fluctuation in glucose levels.

In addition to dermatologic reactions, allergic reactions such as angioedema, arthralgia, myalgia and vasculitis have been reported.

OVERDOSAGE

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displayName: Overdosage Section
FDA Article Code: 34088-5

Overdosage of sulfonylureas, including glyburide tablets, can produce hypoglycemia. Mild hypoglycemic symptoms, without loss of consciousness or neurological 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 which 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.

DOSAGE AND ADMINISTRATION

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displayName: Dosage & Administration Section
FDA Article Code: 34068-7

Patients should be retitrated when transferred from micronized glyburide tablets or other oral hypoglycemic agents. (See PRECAUTIONS).

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

HOW SUPPLIED

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displayName: How Supplied Section
FDA Article Code: 34069-5

Glyburide Tablets, USP are supplied as follows:

Glyburide Tablets 1.25 mg (White to off white, round, flat, beveled edge tablets with scoreline in between ‘2’ & ‘9’ on one side and ‘A’ debossed on other side.) 

         Bottles of 50                       NDC 57237-020-50 (Child Resistant Closure)
         Bottles of 100                     NDC 57237-020-01 (Child Resistant Closure)

Glyburide Tablets 2.5 mg (White to off white, round, flat, beveled edge tablets with scoreline in between ‘3’ & ‘0’ on one side and ‘A’ debossed on other side.)
         
         Bottles of 100                     NDC 57237-021-01 (Child Resistant Closure)
         Bottles of 500                     NDC 57237-021-05 (Non Child Resistant Closure)
         Bottles of 1000                  NDC 57237-021-99 (Non Child Resistant Closure)

Glyburide Tablets
5 mg (White to off white, round, flat, beveled edge tablets with scoreline in between ‘3’ & ‘1’ on one side and ‘A’ debossed on other side.)
         
         Bottles of 100                     NDC 57237-022-01 (Child Resistant Closure)
         Bottles of 500                     NDC 57237-022-05 (Non Child Resistant Closure)
         Bottles of 1000                  NDC 57237-022-99 (Non Child Resistant Closure)

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Dispensed in well closed containers with safety closures. Keep container tightly closed.

Distributed by:
Citron Pharma LLC

Suite – 1101
2 Tower Center Blvd
East Brunswick NJ 08816

Code No.: DRUGS/AP/19/1993
Made in India

Revised: 07/2015

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL – 1.25 mg (100 Tablet Bottle)

id: 2f8a39c0-d7d4-4f69-906c-00d80098c715
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

100 Tablets                  NDC 57237-020-01

GlyBURIDE Tablets, USP

(nonmicronized)

1.25 mg

Rx only                                             Citron Pharma

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL – 2.5 mg (100 Tablet Bottle)

id: 425b7bcc-ca97-460d-a8a8-fd9345bdedf5
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

100 Tablets                  NDC 57237-021-01

GlyBURIDE Tablets, USP

(nonmicronized)

2.5 mg

Rx only                                             Citron Pharma

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL – 5 mg (100 Tablet Bottle)

id: 883afa25-0b6d-449a-8d47-1c8bd9d73c42
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

100 Tablets                  NDC 57237-022-01

GlyBURIDE Tablets, USP

(nonmicronized)

5 mg

Rx only                                             Citron Pharma