No

Antidiabetic Agent (Sulfonylurea)

Management of noninsulin-dependent diabetes mellitus (type 2)

C

Clinical effects on the fetus: 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.

Breast-feeding/lactation: No data available

Hypersensitivity to glyburide or any component, or other sulfonamides; type 1 diabetes mellitus, diabetic ketoacidosis with or without coma

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.

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (glyburide daily doses >2.5 mg).

>10%:

Central nervous system: Headache, dizziness

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

Ocular: Blurred vision

1% to 10%: Dermatologic: Pruritus, rash, urticaria, photosensitivity reaction

<1%: Hypoglycemia, nocturia, leukopenia, thrombocytopenia, hemolytic anemia, aplastic anemia, bone marrow suppression, agranulocytosis, cholestatic jaundice, arthralgia, paresthesia, diuretic effect

Symptoms of overdose include severe hypoglycemia, seizures, cerebral damage, tingling of lips and tongue, nausea, yawning, confusion, agitation, tachycardia, sweating, convulsions, stupor, and coma

Intoxications with sulfonylureas can cause hypoglycemia and are best managed with glucose administration (oral for milder hypoglycemia or by injection in more severe forms)

CYP3A3/4 enzyme substrate

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

Alcohol 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

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

Onset of action: Oral: Insulin levels in the serum begin to increase within 15-60 minutes after a single dose

Duration: Up to 24 hours

Metabolism: To one moderately active and several inactive metabolites

Plasma protein binding: High (>99%)

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

Time to peak serum concentration: Adults: Within 2-4 hours

Oral:

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.

At higher dosages, sulfonylureas may block the ATP-sensitive potassium channels, which may correspond to an increased risk of cardiovascular events. In May, 2000, the National Diabetes Center issued a warning to avoid the use of sulfonylureas at higher dosages (glipizide daily doses >2.5 mg); see Warnings/Precautions.

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

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

Alcohol: A disulfiram-like reaction characterized by flushing, headache, nausea, vomiting, sweating, or tachycardia; avoid use

Food: Food does not affect absorption; glyburide may be taken with food

Glucose: Decreases blood glucose concentration. Hypoglycemia may occur. Educate patients how to detect and treat hypoglycemia. Monitor for signs and symptoms of hypoglycemia. Administer glucose if necessary. Evaluate patient's diet and exercise regimen. May need to decrease or discontinue dose of sulfonylurea.

Sodium: Reports of hyponatremia and SIADH. Those at increased risk include patients on medications or who have medical conditions that predispose them to hyponatremia. Monitor sodium serum concentration and fluid status. May need to restrict water intake.

Signs and symptoms of hypoglycemia, fasting blood glucose, hemoglobin A_1c, fructosamine

Target range: Adults:

Glycosylated hemoglobin: <7%

Dizziness is common

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

No information available to require special precautions

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

This medication is used to control diabetes; it is not a cure. Other components of treatment plan are important: follow prescribed diet, medication, and exercise regimen. 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. Inform prescriber of all other prescription or OTC medications you are taking; do not introduce new medication without consulting prescriber. Do not take other medication within 2 hours of this medication unless so advised by prescriber. If you experience hypoglycemic reaction, contact prescriber immediately. Maintain regular dietary intake and exercise routine and always carry quick source of sugar with you. You may be more sensitive to sunlight (use sunscreen, wear protective clothing and eyewear, and avoid direct sunlight). You may experience side effects during first weeks of therapy (headache, nausea); consult prescriber if these persist. Report severe or persistent side effects, extended vomiting or flu-like symptoms, skin rash, easy bruising or bleeding, or change in color of urine or stool. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Do not breast-feed.

Patients who are anorexic or NPO, may need to have their dose held to avoid hypoglycemia

Tablet (Diabeta®, Micronase®): 1.25 mg, 2.5 mg, 5 mg

Tablet, micronized (Glynase™ PresTab™): 1.5 mg, 3 mg, 4.5 mg, 6 mg

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

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

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.

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.