MICRONASE Tablets contain glyburide, which is an oral blood-glucose-lowering drug of the sulfonylurea class. Glyburide is a white, crystalline compound, formulated as MICRONASE Tablets of 1.25, 2.5, and 5 mg strengths for oral administration. Inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate, magnesium stearate, microcrystalline cellulose, sodium alginate, talc. In addition, the 2.5 mg contains aluminum oxide and FD&C Red No. 40 and the 5 mg contains aluminum oxide and FD&C Blue No. 1. 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.

MICRONASE is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

There is no fixed dosage regimen for the management of diabetes mellitus with MICRONASE Tablets 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, ie, inadequate lowering of blood glucose at the maximum recommended dose of medication; and to detect secondary failure, ie, 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 MICRONASE may be sufficient during periods of transient loss of control in patients usually controlled well on diet.

Usual Starting Dose

The usual starting dose of MICRONASE Tablets is 2.5 to 5 mg daily, administered with breakfast or the first main meal. Those patients who may be more sensitive to hypoglycemic drugs should be started at 1.25 mg daily. (See PRECAUTIONS section for patients at increased risk.) Failure to follow an appropriate dosage regimen may precipitate hypoglycemia. Patients who do not adhere to their prescribed dietary and drug regimen are more prone to exhibit unsatisfactory response to therapy.

Transfer From Other Hypoglycemic Therapy Patients Receiving Other Oral Antidiabetic Therapy

Transfer of patients from other oral antidiabetic regimens to MICRONASE should be done conservatively and the initial daily dose should be 2.5 to 5 mg. When transferring patients from oral hypoglycemic agents other than chlorpropamide to MICRONASE, no transition period and no initial or priming dose are necessary. When transferring patients from chlorpropamide, particular care should be exercised during the first two weeks because the prolonged retention of chlorpropamide in the body and subsequent overlapping drug effects may provoke hypoglycemia.

Patients Receiving Insulin

Some Type II diabetic patients being treated with insulin may respond satisfactorily to MICRONASE. If the insulin dose is less than 20 units daily, substitution of MICRONASE Tablets 2.5 to 5 mg as a single daily dose may be tried. If the insulin dose is between 20 and 40 units daily, the patient may be placed directly on MICRONASE Tablets 5 mg daily as a single dose. If the insulin dose is more than 40 units daily, a transition period is required for conversion to MICRONASE. In these patients, insulin dosage is decreased by 50% and MICRONASE Tablets 5 mg daily is started. Please refer to Titration to Maintenance Dose for further explanation.

Titration to Maintenance Dose

The usual maintenance dose is in the range of 1.25 to 20 mg daily, which may be given as a single dose or in divided doses (See Dosage Interval section). Dosage increases should be made in increments of no more than 2.5 mg at weekly intervals based upon the patient's blood glucose response.

No exact dosage relationship exists between MICRONASE and the other oral hypoglycemic agents. Although patients may be transferred from the maximum dose of other sulfonylureas, the maximum starting dose of 5 mg of MICRONASE Tablets should be observed. A maintenance dose of 5 mg of MICRONASE Tablets provides approximately the same degree of blood glucose control as 250 to 375 mg chlorpropamide, 250 to 375 mg tolazamide, 500 to 750 mg acetohexamide, or 1000 to 1500 mg tolbutamide. When transferring patients receiving more than 40 units of insulin daily, they may be started on a daily dose of MICRONASE Tablets 5 mg concomitantly with a 50% reduction in insulin dose. Progressive withdrawal of insulin and increase of MICRONASE in increments of 1.25 to 2.5 mg every 2 to 10 days is then carried out. During this conversion period when both insulin and MICRONASE are being used, hypoglycemia may rarely occur. During insulin withdrawal, patients should test their urine for glucose and acetone at least three times daily and report results to their physician. The appearance of persistent acetonuria with glycosuria indicates that the patient is a Type I diabetic who requires insulin therapy.

Concomitant Glyburide and Metformin Therapy

MICRONASE Tablets should be added gradually to the dosing regimen of patients who have not responded to the maximum dose of metformin monotherapy after four weeks (see Usual Starting Dose and Titration to Maintenance Dose). Refer to metformin package insert.

With concomitant glyburide and metformin therapy, the desired control of blood glucose may be obtained by adjusting the dose of each drug. However, attempts should be made to identify the optimal dose of each drug needed to achieve this goal. With concomitant glyburide and metformin therapy, the risk of hypoglycemia associated with sulfonylurea therapy continues and may be increased. Appropriate precautions should be taken (see PRECAUTIONS section).

Maximum Dose

Daily doses of more than 20 mg are not recommended.

Dosage Interval

Once-a-day therapy is usually satisfactory. Some patients, particularly those receiving more than 10 mg daily, may have a more satisfactory response with twice-a-day dosage.

Specific Patient Populations

MICRONASE is not recommended for use in pregnancy or for use in pediatric patients.

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.)

MICRONASE Tablets are supplied as follows:

MICRONASE Tablets 1.25 mg (White, Round, Scored, imprinted MICRONASE 1.25)

Bottles of 100 NDC 0009-0131-01

MICRONASE Tablets 2.5 mg (Dark Pink, Round, Scored, imprinted MICRONASE 2.5)

Bottles of 100 NDC 0009-0141-01
Bottles of 1000 NDC 0009-0141-03
Unit Dose Pkg of 100 NDC 0009-0141-02

MICRONASE Tablets 5 mg (Blue, Round, Scored imprinted MICRONASE 5)

Bottles of 30 NDC 0009-0171-11
Bottles of 60 NDC 0009-0171-12
Bottles of 100 NDC 0009-0171-05
Bottles of 500 NDC 0009-0171-06
Bottles of 1000 NDC 0009-0171-07
Unit Dose Pkg of 100 NDC 0009-0171-03

Store at controlled room temperature 20° to 25°Cclosures. Keep container tightly closed.

Distributed by: Pharmacia & Upjohn Co., A division of Pfizer Labs, NY, NY 10017. September 2008. FDA revision date: 10/27/2008

Hypoglycemia

See PRECAUTIONS and OVERDOSAGE Sections.

Gastrointestinal Reactions

Cholestatic jaundice and hepatitis may occur rarely; MICRONASE Tablets should be discontinued if this occurs.

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

Gastrointestinal disturbances, eg, 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, eg, 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 MICRONASE; 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, 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 MICRONASE 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.

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

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

A possible interaction between glyburide and ciprofloxacin, a fluoroquinolone antibiotic, has been reported, resulting in a potentiation of the hypoglycemic action of glyburide. The mechanism for this interaction is not known.

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.

Metformin

In a single-dose interaction study in NIDDM subjects, decreases in glyburide AUC and Cmax were observed, but were highly variable.

The single-dose nature of this study and the lack of correlation between glyburide blood levels and pharmacodynamic effects, makes the clinical significance of this interaction uncertain. Coadministration of glyburide and metformin did not result in any changes in either metformin pharmacokinetics or pharmacodynamics.

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.

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 MICRONASE 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.

General

Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with MICRONASE or any other anti-diabetic drug.

Hypoglycemia

All sulfonylureas are capable of producing severe hypoglycemia. Proper patient selection and dosage and instructions are important to avoid hypoglycemic episodes. Renal or hepatic insufficiency may cause elevated drug levels of glyburide 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. The risk of hypoglycemia may be increased with combination therapy.

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 MICRONASE and administer insulin.

The effectiveness of any hypoglycemic drug, including MICRONASE, 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 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 MICRONASE is first given. Adequate adjustment of dose and adherence to diet should be assessed before classifying a patient as a secondary failure.

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 MICRONASE 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 MICRONASE or other antidiabetic medications. Maintenance or discontinuation of MICRONASE or other antidiabetic medications should be based on clinical judgment using regular clinical and laboratory evaluations.

Laboratory Tests

Therapeutic response to MICRONASE Tablets should be monitored by frequent urine glucose tests and periodic blood glucose tests. Measurement of glycosylated hemoglobin levels may be helpful in some patients.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Studies in rats at doses up to 300 mg/kg/day for 18 months showed no carcinogenic effects. Glyburide is nonmutagenic when studied in the Salmonella microsome test (Ames test) and in the DNA damage/alkaline elution assay. No drug related effects were noted in any of the criteria evaluated in the two year oncogenicity study of glyburide in mice.

Pregnancy

Teratogenic Effects

Pregnancy Category B

Reproduction studies have been performed in rats and rabbits at doses up to 500 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to glyburide. There are, however, no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

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 as close to normal as possible.

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 MICRONASE is used during pregnancy, it should be discontinued at least two weeks before the expected delivery date.

Nursing Mothers

Although it is not known whether glyburide 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.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Elderly patients are particularly susceptible to the hypoglycemic action of glucose lowering drugs. Hypoglycemia may be difficult to recognize in the elderly (see PRECAUTIONS). The initial and maintenance dosing should be conservative to avoid hypoglycemic reactions (see DOSAGE AND ADMINISTRATION). Elderly patients are prone to develop renal insufficiency, which may put them at risk of hypoglycemia. Dose selection should include assessment of renal function.

Overdosage of sulfonylureas, including MICRONASE 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.

MICRONASE Tablets are contraindicated in patients with:

1. Known hypersensitivity or allergy to the drug.
2. Diabetic ketoacidosis, with or without coma. This condition should be treated with insulin.
3. Type I diabetes mellitus.

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 MICRONASE, may become unresponsive or poorly responsive over time. Alternatively, MICRONASE 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 MICRONASE Tablets.

Pharmacokinetics

Single dose studies with MICRONASE Tablets in normal subjects demonstrate significant absorption of glyburide within one hour, peak drug levels at about four hours, and low but detectable levels at twenty-four hours. Mean serum levels of glyburide, as reflected by areas under the serum concentration-time curve, increase in proportion to corresponding increases in dose. Multiple dose studies with MICRONASE in diabetic patients demonstrate drug level concentration-time curves similar to single dose studies, indicating no buildup of drug in tissue depots. The decrease of glyburide in the serum of normal healthy individuals is biphasic; the terminal half-life is about 10 hours. In single dose studies in fasting normal subjects, the degree and duration of blood glucose lowering is proportional to the dose administered and to the area under the drug level concentration-time curve. The blood glucose lowering effect persists for 24 hours following single morning doses in nonfasting diabetic patients. Under conditions of repeated administration in diabetic patients, however, there is no reliable correlation between blood drug levels and fasting blood glucose levels. A one year study of diabetic patients treated with MICRONASE showed no reliable correlation between administered dose and serum drug level. The major metabolite of glyburide is the 4-transhydroxy derivative. A second metabolite, the 3-cishydroxy derivative, also occurs. These metabolites probably contribute no significant hypoglycemic action in humans since they are only weakly active (1/400th and 1/40th as active, respectively, as glyburide) in rabbits.

Glyburide is excreted as metabolites in the bile and urine, approximately 50% by each route. This dual excretory pathway is qualitatively different from that of other sulfonylureas, which are excreted primarily in the urine.

Sulfonylurea drugs are extensively bound to serum proteins. Displacement from protein binding sites by other drugs may lead to enhanced hypoglycemic action. In vitro , the protein binding exhibited by glyburide is predominantly non-ionic, whereas that of other sulfonylureas (chlorpropamide, tolbutamide, tolazamide) is predominantly ionic. Acidic drugs such as phenylbutazone, warfarin, and salicylates displace the ionic-binding sulfonylureas from serum proteins to a far greater extent than the non-ionic binding glyburide. It has not been shown that this difference in protein binding will result in fewer drug-drug interactions with MICRONASE Tablets in clinical use.

Patients should be informed of the potential risks and advantages of MICRONASE and of alternative modes of therapy. They also should be informed about the importance of adherence 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.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

GLYBURIDE - ORAL

(GLY-byur-ide)

COMMON BRAND NAME(S): Diabeta, Glycron, Glynase, Micronase

USES: Glyburide is an anti-diabetic drug (sulfonylurea-type) used along with a proper diet and exercise program to control high blood sugar. It is used in patients with type 2 diabetes (non-insulin-dependent diabetes). It works by stimulating the release of your body's natural insulin. Effectively controlling high blood sugar helps prevent heart disease, strokes, kidney disease, blindness, and circulation problems, as well as sexual function problems (impotence).

HOW TO USE: Take this medication by mouth with breakfast or the first main meal, usually once daily; or use as directed by your doctor. Some patients, especially those taking higher doses, may be directed to take this drug twice a day. The dosage is based on your medical condition and response to therapy.

Use this medication regularly in order to get the most benefit from it. To help you remember, use it at the same time(s) each day. Monitor blood glucose levels on a regular basis. Inform your doctor if your blood glucose measurements are too high or too low.

SIDE EFFECTS: Nausea, heartburn, stomach fullness, and weight gain may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these highly unlikely but very serious side effects occur: persistent sore throat or fever, easy bleeding or bruising, stomach pain, yellowing eyes or skin, dark urine, unusual tiredness or weakness, unusual or sudden weight gain, mental/mood changes, swelling of the hands or feet, seizures.

This medication can cause low blood sugar (hypoglycemia). This effect may occur if you do not consume enough calories (from food, juices, fruit, etc.). The symptoms include chills, cold sweat, blurred vision, dizziness, drowsiness, shaking, rapid heart rate, weakness, headache, fainting, tingling of the hands or feet, or hunger. It is a good habit to carry glucose tablets or gel to treat low blood sugar. If you are in a situation where you don't have these reliable forms of glucose, eat a quick source of sugar such as table sugar, honey, or candy, or drink a glass of orange juice or non-diet soda to quickly raise your blood sugar level. Tell your doctor immediately about the reaction. To help prevent hypoglycemia, eat meals on a regular schedule and do not skip meals.

Symptoms of high blood sugar (hyperglycemia) include thirst, increased urination, confusion, drowsiness, flushing, rapid breathing, or fruity breath odor. If these symptoms occur, tell your doctor immediately. Your medication dosage may need to be increased.

An allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking glyburide, tell your doctor or pharmacist if you are allergic to it or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: metabolic conditions (e.g., diabetic ketoacidosis).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: liver disease, kidney disease, thyroid disease, certain hormonal conditions (adrenal/pituitary insufficiency, SIADH-syndrome of inappropriate secretion of antidiuretic hormone), electrolyte imbalance (hyponatremia).

You may experience blurred vision, dizziness, or drowsiness due to extremely low or high blood sugar levels; use caution engaging in activities requiring alertness such as driving or using machinery.

Limit alcohol while taking this medication because it can increase the risk of developing hypoglycemia. Rarely, alcohol can interact with glyburide and cause a serious reaction (disulfiram-like reaction) with symptoms such as facial flushing, nausea, vomiting, dizziness, or stomach pain. Consult your doctor or pharmacist about the safe use of alcohol.

During times of stress, such as fever, infection, injury or surgery, it may be more difficult to control your blood sugar. Consult your doctor, as a change in your medication may be required.

This medication may make you more sensitive to the sun. Avoid prolonged sun exposure, tanning booths or sunlamps. Use a sunscreen and wear protective clothing when outdoors.

Caution is advised when using this drug in the elderly because they may be more sensitive to the effects of the drug, especially hypoglycemia.

This medication should be used only when clearly needed during pregnancy. Insulin treatment may be preferred. If glyburide is used, it may be switched to insulin at least 2 weeks before the expected delivery date because of glyburide's risk of low blood sugar in your newborn. Discuss the risks and benefits with your doctor.

Based on information from related drugs, this medication may pass into breast milk. Therefore, breast-feeding while using this medication is not recommended.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because a very serious interaction may occur: bosentan.

If you are currently using this medication, tell your doctor or pharmacist before starting glyburide.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription products you may use, especially of: other diabetes drugs (e.g., insulin, metformin), aspirin or aspirin-like drugs (e.g., salicylates, NSAIDs such as ibuprofen, phenylbutazone), azole antifungals (e.g., fluconazole), birth control pills, "blood thinners" (e.g., warfarin), calcium channel blockers (e.g., diltiazem), chloramphenicol, clofibrate, colesevelam, corticosteroids (e.g., prednisone), decongestants (e.g., pseudoephedrine), diazoxide, diet pills, epinephrine, estrogens, isoniazid, MAO inhibitors (e.g., furazolidone, linezolid, moclobemide, phenelzine procarbazine, selegiline, isocarboxazid, tranylcypromine), niacin, phenothiazines (e.g., promethazine), phenytoin, probenecid, quinolone antibiotics (e.g., ciprofloxacin), rifampin, sulfonamides (e.g., sulfa antibiotics), thyroid drugs, "water pills" (diuretics such as hydrochlorothiazide, furosemide), fenugreek, ginseng.

Beta-blocker medications (e.g., metoprolol, propranolol, glaucoma eye drops such as timolol) may prevent the fast/pounding heartbeat you would usually feel when your blood sugar level falls too low (hypoglycemia). Other symptoms of low blood sugar such as dizziness, hunger, or sweating are unaffected by these drugs.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. Symptoms of overdose may include: shakiness, rapid heartbeat, sweating, loss of consciousness.

NOTES: Do not share this medication with others.

It is recommended you attend a diabetes education program to understand diabetes and all the important aspects of its treatment including meals/diet, exercise, personal hygiene, medications and getting regular eye, foot and medical exams.

Keep all medical appointments. Laboratory and/or medical tests (e.g., liver and kidney function tests, fasting blood glucose, hemoglobin A1c, complete blood counts) will be performed to monitor for side effects and response to therapy. Regularly check your blood or urine for sugar, as directed by your doctor or pharmacist.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Storage temperature ranges differ according to different manufacturers, so consult your pharmacist for more information. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For enrollment information call MedicAlert at 1-800-854- 1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.