glyburide
DiaBeta, Glynase PresTab, Micronase

Available forms
Available by prescription only
Tablets: 1.25 mg, 2.5 mg, 5 mg
Tablets (micronized): 1.5 mg, 3 mg, 4.5 mg, 6 mg

Indications and dosages
 Adjunct to diet to lower blood glucose levels in patients with type 2 diabetes mellitus. Adults: Initially, 2.5 to 5 mg P.O. daily with breakfast. Start patients who are more sensitive to hypoglycemic drugs at 1.25 mg daily. Usual maintenance dosage is 1.25 to 20 mg daily, either as a single dose or in divided doses.
 For micronized tablets, initially give 1.5 to 3 mg P.O. with breakfast. Usual maintenance dosage is 0.75 to 12 mg P.O. daily.
≡ Dosage adjustment. For elderly, debilitated, or malnourished patients or those with renal or liver dysfunction, start with 1.25 mg once daily.
 To replace insulin therapy. Adults: If insulin dose is more than 40 units daily, patient may be started on 5 mg of glyburide daily plus 50% of the insulin dose. Patients maintained on less than 20 units daily should receive 2.5 to 5 mg daily; those maintained on 20 to 40 units daily should receive 5 mg daily. In all patients, glyburide is substituted and insulin discontinued abruptly.
 For micronized tablets, if insulin dose is more than 40 units daily, give 3 mg P.O. with a 50% reduction in insulin. Patients maintained on 20 to 40 units daily should receive 3 mg P.O. as a single daily dose; those maintained on less than 20 units daily should receive 1.5 to 3 mg daily as a single dose.

Pharmacodynamics
Antidiabetic action: Glyburide decreases blood glucose levels by stimulating insulin release from functioning beta cells in the pancreas. After prolonged administration, hypoglycemic effects appear to be related to extrapancreatic effects, possibly including reduction of basal hepatic glucose production and enhanced peripheral sensitivity to insulin. The latter may result either from an increase in the number of insulin receptors or from changes in events subsequent to insulin binding.

Pharmacokinetics
Absorption: Almost completely absorbed from GI tract. A micronized tablet results in significant absorption; a 3-mg micronized tablet provides blood levels similar to a 5-mg conventional tablet.
Distribution: 99% protein-bound. Distribution isn’t fully understood.
Metabolism: Metabolized completely by the liver to inactive metabolites.
Excretion: Excreted as metabolites in urine and feces in equal proportions. Duration of action is 24 hours, and half-life is 10 hours.

Contraindications and precautions
Contraindicated in pregnant and breast-feeding women, patients hypersensitive to drug, and patients with diabetic ketoacidosis with or without coma. Use cautiously in patients with impaired renal or hepatic function and in elderly, malnourished, or debilitated patients.

Interactions
Drug-drug. Adrenocorticoids, amphetamines, baclofen, corticotropin, diazoxide, epinephrine, ethacrynic acid, furosemide, glucagon, glucocorticoids, phenytoin, rifampin, thiazide diuretics, thyroid hormones, triamterene: Increases blood glucose levels. Dosage adjustments may be required.
Anabolic steroids, chloramphenicol, clofibrate, guanethidine, insulin, MAO inhibitors, probenecid, salicylates, sulfonamides: Enhances hypoglycemic effect by displacing glyburide from its protein-binding sites. Monitor glucose levels and patient carefully.
Anticoagulants: May increase plasma levels of both drugs and, after continued therapy, decrease plasma levels and anticoagulant effect. Monitor blood glucose and PT.
Beta blockers, including ophthalmics: Increases risk of hypoglycemia. Use together cautiously.
Hydantoins: May increase hydantoin levels. Monitor blood levels.
Drug-lifestyle. Alcohol use: Alters glycemic control, most commonly hypoglycemia. May also cause a disulfiram-like reaction consisting of nausea, vomiting, abdominal cramps, and headaches. Discourage alcohol use.
Smoking: May increase corticosteroid release; patients who smoke may need higher glyburide dosage. Discourage smoking.

Adverse reactions
EENT: changes in accommodation, blurred vision.
GI: nausea, epigastric fullness, heartburn.
Hematologic: leukopenia, hemolytic anemia, agranulocytosis, thrombocytopenia, aplastic anemia.
Hepatic: cholestatic jaundice, hepatitis.
Metabolic: hypoglycemia.
Musculoskeletal: arthralgia, myalgia.
Skin: rash, pruritus, other allergic reactions.
Other: angioedema, SIADH.

Effects on lab test results
• May increase BUN, alkaline phosphatase, bilirubin, AST, ALT, and cholesterol levels. May decrease glucose levels.
• May decrease hemoglobin, hematocrit, and WBC, platelet, and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include low blood glucose levels, tingling of lips and tongue, hunger, nausea, decreased cerebral function (lethargy, confusion, agitation, and nervousness), increased sympathetic activity (tachycardia, sweating, and tremor) and, ultimately, seizures, stupor, and coma.
 Mild hypoglycemia, without loss of consciousness or neurologic findings, responds to treatment with oral glucose and dosage adjustments. Patient with severe hypoglycemia should be hospitalized immediately. If hypoglycemic coma is suspected, patient should receive rapid injection of dextrose 50%, followed by a continuous infusion of dextrose 10% at a rate to maintain blood glucose levels greater than 100 mg/dl. Monitor patient for 24 to 48 hours.

Special considerations
• To improve control in patients receiving 10 mg daily or more, divided doses, usually given before the morning and evening meals, are recommended.
• Some patients taking glyburide may have their glucose levels controlled effectively on a once-daily regimen, whereas others show better response with divided dosing.
• Glyburide is a second generation sulfonylurea oral antidiabetic. It appears to cause fewer adverse reactions than first-generation drugs.
• Drug has a mild diuretic effect that may be useful in patients with chronic heart failure or cirrhosis.
• Oral antidiabetics may increase the risk of CV mortality compared with diet or diet and insulin therapy.
• Monitor blood glucose frequently for 24 to 72 hours since hypoglycemia may occur after apparent clinical recovery.
• When substituting glyburide for chlorpropamide, monitor patient closely during the first week because of the prolonged retention of chlorpropamide in the body.
• Monitor blood glucose, urine glucose, and ketone levels.
Pediatric patients
• Glyburide is ineffective in type 1 diabetes.
• Safety and efficacy in children haven’t been established.
Geriatric patients
• These patients may be more sensitive to drug effects because of reduced metabolism and elimination.
• Hypoglycemia causes more neurologic symptoms in elderly patients.

Patient education
• Emphasize importance of following prescribed diet, exercise, and medical regimen.
• Advise patient to avoid alcohol and alcohol-containing products while taking glyburide.
• Suggest that patient take drug with food if GI upset occurs.
• Teach patient how to monitor blood glucose, urine glucose, and ketone levels.
• Inform patient of the signs and symptoms of hyperglycemia and hypoglycemia and what to do if they occur.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use