glyburide (Rx)

Frequency Not Defined

Angioedema

Urticaria

Rash

Morbilliform eruptions

Pruritus

Photosensitivity reaction

Heartburn

Vasculitis

Disulfiram-like reaction

Hyponatremia

Nocturia

Agranulocytosis

Hemolytic anemia

Pancytopenia

Thrombocytopenia

Porphyria cutanea tarda

Arthralgia

Paresthesia

Myalgia

Blurred vision

Diuretic effect (minor)

Hypoglycemia

Nausea/vomiting

Cholestatic jaundice and hepatitis, which occur only rarely, may progress to liver failure

Weight gain

Bullous reactions, erythema multiforme, and exfoliative dermatitis

Contraindications

Hypersensitivity; sulfa allergy

Type 1 diabetes

Diabetic ketoacidosis with or without coma

Coadministration with bosentan; increased risk of hepatotoxicity

Cautions

Risk of hypoglycemia increases when caloric intake is deficient, when more than one glucose-lowering agent used, when ethanol is ingested, or after severe or prolonged exercise; hypoglycemia is also morelikely to occur in elederly patients, malnourished or debilitated patients, and in patients with adrenal and/or pituitary insufficiency, and patients with severe hepatic and hepatic impairment

Concerns for cross-reactivity between agents containing sulfonamide products has been reported for patients with prior allergic reactions to any compound with the sulfonamide structure SO2NH2; an expanding understanding of allergic mechanisms suggest that cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least the potential is extremely low

Caution in pregnancy/lactation

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; latest studies, however, do not support association

Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents; use caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency

There are no clinical studies establishing conclusive evidence of macrovascular risk reduction with anti-diabetic drugs

Use of glyburide not recommended in chronic kidney disease; metabolism and excretion of glyburide may be slowed in aptients with renal impairment and its active metabolites, causing accumulation in advanced renal insufficiency; prolonged hypoglycemia could occur

It may be necessary to discontinue therapy and administer insulin if patient exposed to stress

Micronized tablet formulation is not bioequivalent to conventional glyburide tablets; when transferring patient to a different glyburide formulation, retitrate the dose

Beta cell destruction may occur following prolonged use of therapy, which may result in loss of treatment efficacy in type 2 diabetes mellitus; discontinue therapy if loss of efficacy occurs in patients who were previously responding to treatment and no contributing factors can be identified

All sulfonylureas are capable of producing severe hypoglycemia

Pregnancy category: C

Lactation: Not known if crosses into breast milk; avoid use in nursing women

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Initial effect is to increase beta-cell insulin secretion

May also decrease rate of hepatic glucose production and increase insulin receptor sensitivity

Absorption

Bioavailability: Variable, depending on oral dosage form

Onset: 15-60 min after a single dose (increase in serum insulin levels)

Duration: <24 hr

Vd: 9-10 L

Peak serum time: 2-4 hr (adults)

Distribution

Protein bound: 99%

Metabolism

Metabolized extensively in the liver to less-active metabolites

Metabolites: 4-trans-hydroxyglyburide, 3-cis-hydroxyglyburide (active)

Elimination

Half-life: 10 hr (DiaBeta); 4 hr (Glynase, PresTab)

Excretion: Urine (50%), feces (50%)