Glyburide

Action

Increases insulin binding and sensitivity at receptor sites, stimulating insulin release from beta cells in pancreas and reducing blood glucose level. Also decreases production of basal glucose in liver, enhances sensitivity of peripheral tissue to insulin, inhibits platelet aggregation, and causes mild diuresis.

Availability

Tablets: 1.25 mg, 2.5 mg, 5 mg

Tablets (micronized): 1.5 mg, 3 mg, 6 mg

Indications and dosages

➣ To control blood glucose in type 2 (non-insulin-dependent) diabetes mellitus in patients who have some pancreatic function and don't respond to diet therapy

Adults: Initially, 2.5 to 5 mg (regular tablets) P.O. daily; range is 1.25 to 20 mg/day as a single dose or in divided doses. Or initially, 1.5 to 3 mg (micronized tablets) P.O. daily, with range of 0.75 to 12 mg/day; give dosages above 6 mg in two divided doses.

➣ Conversion from insulin therapy

Adults: If patient takes less than 20 units of insulin daily, give 2.5 to 5 mg glyburide daily; with insulin dosage of 20 to 40 units/day, give 5 mg glyburide; with insulin dosage above 40 units/day, give 5 mg glyburide daily or 3 mg (micronized tablets) P.O. daily and reduce insulin dosage by 50%.

Dosage adjustment

• Hepatic or renal failure

• Elderly patients

Contraindications

• Hypersensitivity to drug

• Type 1 (insulin-dependent) diabetes

• Severe renal, hepatic, thyroid or other endocrine disease

• Pregnancy or breastfeeding

Precautions

Use cautiously in:

• mild to moderate hepatic, renal, or cardiovascular disease; impaired thyroid, pituitary, or adrenal function

• infection, stress, or dietary changes

• elderly patients.

Administration

☞ Know that micronized glyburide is not bioequivalent to regular glyburide.

• Check baseline creatinine level for normal renal function before giving first dose.

• Give daily dose at breakfast; for patient receiving drug b.i.d., give second dose at dinner.

• Adjust dosage slowly if patient is taking metformin.

Adverse reactions

CNS: dizziness, drowsiness, headache, weakness

CV: increased CV mortality risk

EENT: visual accommodation changes, blurred vision

GI: nausea, vomiting, diarrhea, constipation, cramps, heartburn, epigastric distress, anorexia

Hematologic: aplastic anemia, leukopenia, thrombocytopenia, agranulocytosis, pancytopenia

Hepatic: cholestatic jaundice, hepatitis

Metabolic: hyponatremia, hypoglycemia

Skin: rash, pruritus, urticaria, eczema, erythema, photosensitivity, angioedema

Other: increased appetite

Interactions

Drug-drug. Androgens (such as testosterone), chloramphenicol, clofibrate, guanethidine, MAO inhibitors, nonsteroidal anti-inflammatory drugs (except diclofenac), salicylates, sulfonamides, tricyclic antidepressants: increased risk of hypoglycemia

Beta-adrenergic blockers: altered response to glyburide, requiring increased or decreased dosage; prolonged hypoglycemia (with nonselective agents)

Calcium channel blockers, corticosteroids, estrogens, hydantoins, hormonal contraceptives, isoniazid, nicotinic acid, phenothiazines, phenytoin, rifampin, sympathomimetics, thiazide diuretics, thyroid preparations: decreased hypoglycemic effect of glyburide

Warfarin: initially increased, then decreased, effects of both drugs

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, blood urea nitrogen, cholesterol: increased values

Glucose, granulocytes, hemoglobin, platelets, white blood cells: decreased values

Drug-herbs. Agoral marshmallow, aloe (oral), bitter melon, burdock, chromium, coenzyme Q10, dandelion, eucalyptus, fenugreek: increased hypoglycemic effect

Glucosamine: impaired glycemic control

Drug-behaviors. Alcohol use: disulfiram-like reaction

Patient monitoring

• Monitor blood glucose level, especially during periods of increased stress.

• Monitor CBC and renal function test results.

• If patient is ill or has abnormal laboratory findings, monitor electrolyte, ketone, glucose, pH, lactate dehydrogenase, and pyruvate levels.

• Evaluate cardiovascular status.

Patient teaching

• Advise patient to take daily dose with breakfast (and second dose, if prescribed, with dinner).

• Teach patient how to self-monitor his glucose level as prescribed; tell him to report significant changes.

• Inform patient that he may need supplemental insulin during times of stress or when he can't maintain adequate oral intake.

• Teach patient how to recognize signs and symptoms of hypoglycemia and hyperglycemia.

• Instruct patient to keep sugar source available at all times.

• Encourage patient to drink plenty of fluids.

• Stress importance of diet and exercise in helping to control diabetes.

• Advise patient to wear or carry medical identification stating he has diabetes.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient he'll undergo regular blood testing during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.