Pronunciation

U.S. Brand Names

Diaeta®; Glynase® PresTab®; Micronase®

Synonyms

Diabeta; Glibenclamide; Glybenclamide; Glybenzcyclamide

Generic Available

Yes

Canadian Brand Names

Albert® Glyburide; Apo-Glyburide®; Diaeta®; Euglucon®; Gen-Glybe; Novo-Glyburide; Nu-Glyburide; PMS-Glyburide; ratio-Glyburide

Use

Management of type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Use - Unlabeled/Investigational

Alternative to insulin in women for the treatment of gestational diabetes (11-33 weeks gestation)

Pregnancy Risk Factor

C

Pregnancy Implications

Crosses the placenta. Hypoglycemia; ear defects reported; other malformations reported but may have been secondary to poor maternal glucose control/diabetes. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

Lactation

Excretion in breast milk unknown/contraindicated

Contraindications

Hypersensitivity to glyburide, any component of the formulation, or other sulfonamides; type 1 diabetes mellitus (insulin dependent, IDDM), diabetic ketoacidosis with or without coma

Warnings/Precautions

Elderly: Rapid and prolonged hypoglycemia (>12 hours) despite hypertonic glucose injections have been reported; age and hepatic and renal impairment are independent risk factors for hypoglycemia; dosage titration should be made at weekly intervals. Use with caution in patients with renal and hepatic impairment, malnourished or debilitated conditions, or adrenal or pituitary insufficiency.

Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.

Adverse Reactions

Frequency not defined.

Central nervous system: Headache, dizziness

Dermatologic: Pruritus, rash, urticaria, photosensitivity reaction

Endocrine & metabolic: Hypoglycemia, hyponatremia (SIADH reported with other sulfonylureas)

Gastrointestinal: Nausea, epigastric fullness, heartburn, constipation, diarrhea, anorexia

Genitourinary: Nocturia

Hematologic: Leukopenia, thrombocytopenia, hemolytic anemia, aplastic anemia, bone marrow suppression, agranulocytosis

Hepatic: Cholestatic jaundice, hepatitis

Neuromuscular & skeletal: Arthralgia, paresthesia

Ocular: Blurred vision

Renal: Diuretic effect (minor)

Overdosage/Toxicology

Symptoms of overdose include severe hypoglycemia, seizures, cerebral damage, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma. Intoxication with sulfonylureas can cause hypoglycemia and is best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms).

Drug Interactions

CYP3A4 (weak)

Decreased effect: Thiazides may decrease effectiveness of glyburide

Increased effect: Possible interaction between glyburide and fluoroquinolone antibiotics has been reported resulting in a potentiation of hypoglycemic action of glyburide

Increased toxicity:

Since this agent is highly protein bound, the toxic potential is increased when given concomitantly with other highly protein bound drugs (ie, phenylbutazone, oral anticoagulants, hydantoins, salicylates, NSAIDs, beta-blockers, sulfonamides) - increase hypoglycemic effect

Ethanol increases disulfiram reactions

Phenylbutazone can increase hypoglycemic effects

Certain drugs tend to produce hyperglycemia and may lead to loss of control (ie, thiazides and other diuretics, corticosteroids, phenothiazines, thyroid products, estrogens, oral contraceptives, phenytoin, nicotinic acid, sympathomimetics, calcium channel blocking drugs, and isoniazid)

Possible interactions between glyburide and coumarin derivatives have been reported that may either potentiate or weaken the effects of coumarin derivatives

Ethanol/Nutrition/Herb Interactions

Ethanol: Caution with ethanol (may cause hypoglycemia).

Herb/Nutraceutical: Caution with chromium, garlic, gymnema (may cause hypoglycemia).

Mechanism of Action

Stimulates insulin release from the pancreatic beta cells; reduces glucose output from the liver; insulin sensitivity is increased at peripheral target sites

Pharmacodynamics/Kinetics

Onset of action: Serum insulin levels begin to increase 15-60 minutes after a single dose

Duration:

Protein binding, plasma: >99%

Metabolism: To one moderately active and several inactive metabolites

Half-life elimination: 5-16 hours; may be prolonged with renal or hepatic impairment

Time to peak, serum: Adults: 2-4 hours

Excretion: Feces (50%) and urine (50%) as metabolites

Dosage

Oral:

Adults:

Initial: 2.5-5 mg/day, administered with breakfast or the first main meal of the day. In patients who are more sensitive to hypoglycemic drugs, start at 1.25 mg/day.

Increase in increments of no more than 2.5 mg/day at weekly intervals based on the patient's blood glucose response

Maintenance: 1.25-20 mg/day given as single or divided doses; maximum: 20 mg/day

Elderly: Initial: 1.25-2.5 mg/day, increase by 1.25-2.5 mg/day every 1-3 weeks

Micronized tablets (Glynase™ PresTab™): Adults:

Initial: 1.5-3 mg/day, administered with breakfast or the first main meal of the day in patients who are more sensitive to hypoglycemic drugs, start at 0.75 mg/day. Increase in increments of no more than 1.5 mg/day in weekly intervals based on the patient's blood glucose response.

Maintenance: 0.75-12 mg/day given as a single dose or in divided doses. Some patients (especially those receiving >6 mg/day) may have a more satisfactory response with twice-daily dosing.

Dosing adjustment/comments in renal impairment: Clcr<50 mL/minute: Not recommended

Dosing adjustment in hepatic impairment: Use conservative initial and maintenance doses and avoid use in severe disease

Administration

Administer with meals at the same time each day. Patients who are anorexic or NPO may need to have their dose held to avoid hypoglycemia.

Monitoring Parameters

Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A1c

Reference Range

Target range: Adults:

Fasting blood glucose: <120 mg/dL

Glycosylated hemoglobin: <7%

Dietary Considerations

Should be taken with meals at the same time each day. Dietary modification based on ADA recommendations is a part of therapy. Decreases blood glucose concentration. Hypoglycemia may occur. Must be able to recognize symptoms of hypoglycemia (palpitations, sweaty palms, lightheadedness).

Patient Education

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. This medication is used to control diabetes; it is not a cure. Monitor glucose as recommended by prescriber. Other important components of treatment plan may include prescribed diet and exercise regimen (consult prescriber or diabetic educator). If you experience hypoglycemic reaction, contact prescriber immediately. Always carry quick source of sugar with you. Take exactly as directed, 30 minutes before meal(s) at the same time each day. Do not change dose or discontinue without consulting prescriber. Avoid alcohol while taking this medication; could cause severe reaction. Do not take other medication within 2 hours of this medication unless advised by prescriber. You may experience more sensitivity to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight); headache; or nausea (consult prescriber if these persist). Report severe or persistent side effects; hypoglycemia (palpitations, sweaty palms, lightheadedness); extended vomiting, diarrhea, or constipation; flu-like symptoms; skin rash; easy bruising or bleeding; or change in color of urine or stool. Inform prescriber if you are or intend to become pregnant. Do not breast-feed.

Anesthesia and Critical Care Concerns/Other Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Cardiovascular Considerations

The possibility of higher doses of sulfonylureas eliciting an increase in cardiovascular events, because of their effects on blocking potassium sensitive ATP channels, has been raised. However, there are presently only limited data to support this premise, particularly with newer generation agents. An early study suggested poor cardiovascular outcomes in diabetic patients treated with tolbutamide. Retrospective studies evaluating cardiovascular outcomes following angioplasty and acute myocardial infarction in diabetic patients receiving newer sulfonylureas are inconsistent. Longer-term prospective trials of sulfonylurea therapy, such as the UKPDS, do not reveal any increased cardiovascular mortality.

Dental Health: Effects on Dental Treatment

Glyburide-dependent diabetics (noninsulin dependent, type 2) should be appointed for dental treatment in morning in order to minimize chance of stress-induced hypoglycemia.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness is common

Mental Health: Effects on Psychiatric Treatment

May rarely cause agranulocytosis; use caution with clozapine and carbamazepine; phenothiazines and TCAs may antagonize glimepiride hypoglycemic effects; MAO inhibitors and TCAs may enhance hypoglycemic effects

Dosage Forms

Tablet (Dia

Tablet, micronized (Glynase® PresTab®): 1.5 mg, 3 mg, 6 mg

References

Alexander RW, "Prolonged Hypoglycemia Following Acetohexamide Administration,"Diabetes, 1966, 15(5):362-4.

"A Study of the Effects of Hypoglycemia Agents on Vascular Complications in Patients With Adult-onset Diabetes. VI. Supplementary Report on Nonfatal Events in Patients Treated With Tolbutamide. The University Group Diabetes Program,"Diabetes, 1976, 25(12):1129-53.

Brodows RG, "Benefits and Risks With Glyburide and Glipizide in Elderly NIDDM Patients,"Diabetes Care, 1992, 15(1):75-80.

Cowen DL, Burtis B, and Youmans J, "Prolonged Coma After Acetohexamide Ingestion,"JAMA, 1967, 201(2):141-2.

"Effect of Intensive Blood-Glucose Control With Metformin on Complications in Overweight Patients With Type 2 Diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):854-65.

Garratt KN, Brady PA, Hassinger NL, et al, "Sulfonylurea Drugs Increase Early Mortality in Patients With Diabetes Mellitus After Direct Angioplasty for Acute Myocardial Infarction,"J Am Coll Cardiol, 1999, 33(1):119-24.

Gavin JR 3d, "Glyburide: New Insights Into Its Effects on the Beta Cell and Beyond - Introduction,"Am J Med, 1990, 89(2A):1S-2S.

"Intensive Blood-Glucose Control With Sulphonylureas or Insulin Compared With Conventional Treatment and Risk of Complications in Patients With Type 2 Diabetes (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group,"Lancet, 1998, 352(9131):837-53.

Klamann A, Sarfert P, Launhardt V, et al, "Myocardial Infarction in Diabetic vs Nondiabetic Subjects. Survival and Infarct Size Following Therapy With Sulfonylureas (Glibenclamide),"Eur Heart J, 2000, 21(3):220-9.

Langer O, Conway D, Berkus M, et al, "A Comparison of Glyburide and Insulin in Women With Gestational Diabetes Mellitus,"N Engl J Med, 2000, 343(16):1134-8.

Meinert CL, Knatterud GL, Prout TE, et al, "A Study of the Effects of Hypoglycemic Agents on Vascular Complications in Patients With Adult-Onset Diabetes. II. Mortality Results,"Diabetes, 1970, 19:789-830.

Nadel HL, "Formulary Conversion From Glipizide to Glyburide: A Cost-Minimization Analysis,"Hosp Pharm, 1995, 30:472-74.

Nataas OB and Nesthus I, "Immune Haemolytic Anaemia Induced by Glibenclamide in Selective IgA Deficiency,"Br Med J (Clin Res Ed), 1987, 295(6594):366-7.

O'Keefe JH, Blackstone EH, Sergeant P, et al, "The Optimal Mode of Coronary Revascularization for Diabetics. A Risk-Adjusted Long-Term Study Comparing Coronary Angioplasty and Coronary Bypass Surgery,"Eur Heart J, 1998, 19(11):1696-703.

Pearson JG, "Pharmacokinetics of Glyburide,"Am J Med , 1985, 79(3B):67-71.

Rosenstock J, Corrao PJ, Goldberg RB, et al, "Diabetes Control in the Elderly: A Randomized, Comparative Study of Glyburide Versus Glipizide in Noninsulin-Dependent Diabetes Mellitus,"Clin Ther, 1993, 15(6):1031-40.

Schwinghammer TL, Antal EJ, Kubacka RT, et al, "Pharmacokinetics and Pharmacodynamics of Glyburide in Young and Elderly Nondiabetic Adults,"Clin Pharm, 1991, 10(7):532-8.

Sillence DO and Court JM, "Glibenclamide-Induced Hypoglycemia,"Br Med J, 1975, 3(5981):490-1.

Sonnenblick M and Shilo S, "Glibenclamide Induced Prolonged Hypoglycaemia,"Age Ageing, 1986, 15(3):185-9.

"Standards of Medical Care for Patients With Diabetes Mellitus. American Diabetes Association,"Diabetes Care, 1994, 17(6):616-23.

International Brand Names

Adiabet® (GT, HN, SV); Aglucil® (BR); Albert® Glyburide (CA); Apo-Glyburide® (CA, RO); Azuglucon® (DE); Bastiverit® (DE); Benclamid® (AR); Benclamin® (TH); Betanase® (CZ); Bevoren® (BE, LU); Bnil-5 (TH); Clamide® (SG); Condiabet® (ID); Cytagon® (TH); Daonil® (AR, AT, AU, BD, BE, BR, CH, CL, CR, DK, DO, EC, ES, FR, GB, GT, HK, HN, ID, IE, IL, IN, IT, LU, MX, NL, NO, PA, PT, RU, SE, SG, SI, SV, TH, YU, ZA); Daono® (TH); Debtan® (TH); Diab-Control® (RU); Diabemin Glibenclamida® (AR); Diaben® (BR); Diabenol® (TH); Diabesulf® (EC); Diaeta® (CA); Diabetamide® (GB); Diabexil® (BR); Dia-Eptal® (AT, DE); Dianorm® (TR); Diarom® (RO); Dibelet® (SG, TH); Dibenol® (BD); Diclanil® (TH); Dicon® (BD); Diyaben® (TR); duraglucon® (DE); Euclamin® (PL); Euglamin® (FI); Euglucan® (FR); Euglucon® (AR, AT, BE, BR, CA, CH, CO, CR, CZ, DE, DO, ES, FI, GB, GT, HK, HN, HR, ID, IN, IT, JP, LU, MX, NO, PA, PT, RU, SE, SI, SV, TH); Euglusid® (CL); Gardoton® (AR); G.B.N.® (SG); Gen-Glybe (CA); Gilemal® (AT, HK, HU, RO, RU); Glencamide® (TH); Glib AbZ® (DE); gli-basan® (CH); Glibemide® (JO, RO); Gliben-AZU® (DE); Glibenbeta® (DE); Glibencil® (DO); Glibenclamida Ahimsa® (AR); Glibenclamida® (CL, CO, CR); Glibenclamida Denver® (AR); Glibenclamida Fabra® (AR); Glibenclamida Gen Med® (AR); Glibenclamida L.CH.® (CL); Glibenclamid AL® (DE); Glibenclamida Merck® (CO); Glibenclamida Rigo® (AR); Glibenclamid Basics® (DE); Glibenclamid (BR, NO, RO, RU); Glibenclamid-Cophar® (CH); Glibenclamide® (GB); Glibenclamid Genericon® (AT, HR); Glibenclamid Heumann® (DE); Glibenclamid Pharmavit® (HU); Glibenclamid R.A.N.® (DE); Glibenclamid-ratiopharm® (LU); Glibenclamid Sandoz® (DE); Glibendoc® (DE); Glibenhexal® (DE, LU); Glibenil® (MX); Gliben® (IT, NZ, TH, TR); Glibenklamid NM Pharma® (SE); Glibenklamid® (SI, YU); Gliben Lich® (DE); Glibenorm® (CH); Gliben-Puren N® (DE); Glibens® (CO); gliben von ct® (DE); Glibesifar® (CH); Glibesyn® (SG); Glibetic® (AR, IL, RO, TH); Glibic® (TH); Glibil® (EG, JO, KW, LB, RO, SY); Gliboral® (IT, RO); Glib-ratiopharm® (DE); Glicem® (EC); Glidanil® (AR); Glidiabet® (HK); Gliken® (GB); Glimel® (AU, ID); Glimide® (SG); Glimidstada® (DE); Glitisol® (CY); Glitral® (AR); Gluban® (BD); Gluben 5TM® (RO); Glucal® (MX); Glucamida® (DO); Glucobene® (AT, CZ, HU); Glucolon® (ES); Glucomid® (BG, JO, KW, LB, MA, MY, SY); Glucon® (BD); Gluconic 5® (ID); Gluconil® (BD, TH); Glucoremed® (DE); Glucostad® (AT); Glucotab® (BD); Glucoven® (MX); Glukovital® (DE); Gluzo® (TH); Glyamid® (ID); Glycomin® (ZA); Gon® (AR); Hémi-Daonil® (FR); Hemi-Daonil® (NL); Hexaglucon® (DK); Humedia® (DE); Jutaglucon® (DE); Libraglucil® (EC); Lisaglucon® (BR); Locose® (TH); Maninil® (CZ, DE, PL, RO, RU, YU); Manirom® (RO); Manoglucon® (TH); Med-Glionil® (TH); Melix® (CH); Miglucan® (FR); Nadib® (MX); Norboral® (MX); Nor-Clamida® (DO, GT, HN, PA, SV); Norglicem 5® (ES); Normoglucon® (AT); Novo-Glyburide (CA); Nu-Glyburide (CA); Origlucon® (FI); Pira® (AR); PMS-Glyburide (CA); Praeciglucon® (DE); Prodiabet® (ID); Prodiamel® (ID); ratio-Glyburide (CA); Regulin® (DK); Renabetic® (ID); Semi Daonil® (CH, DE, GB, ID); Semi-Euglucon® (AT, ID); Semi-Euglucon N® (DE); Sugril® (TH); Tiabet® (ID); Uniao Glibenclamida® (BR)