GLYE-byoo-ride

Therapeutic Classification: antidiabetics

Pharmacologic Classification: sulfonylureas

• PO: Type 2 diabetes mellitus (as adjunct to diet and exercise)

• Lowers blood sugar by stimulating the release of insulin from the pancreas and increasing the sensitivity to insulin at receptor sites.
• May also decrease hepatic glucose production.

• Reduction in blood glucose.

Absorption: Well absorbed following oral administration; micronized forms have better absorption.

Distribution: Reaches high concentrations in bile and crosses the placenta.

Metabolism/Excretion: Mostly metabolized by the liver, primarily by the CYP2C9 isoenzyme.

Half-life: 10 hr.

(hypoglycemic activity)

Contraindicated in:

• Hypersensitivity
• Hypersensitivity to sulfonamides (cross-sensitivity may occur)
• Type 1 diabetes
• Diabetic coma or ketoacidosis
• Lactation: Lactation.

Use Cautiously in:

• Severe cardiovascular or hepatic disease
• Glucose 6-phosphate dehydrogenase deficiency (↑ risk of hemolytic anemia)
• Severe renal impairment (↑ risk of hypoglycemia)
• Infection, stress, or changes in diet may alter requirements for control of blood sugar
• Impaired thyroid, pituitary, or adrenal function
• Malnutrition, high fever, prolonged nausea, or vomiting
• OB: Safety not established during pregnancy; insulin recommended during pregnancy
• Pedi: Safety and effectiveness not established in children
• Geri: Appears on Beers list. ↑ risk of prolonged hypoglycemia in older adults. Avoid use as first- or second-line monotherapy or as add-on treatment in older adults unless there are significant barriers to the use of safer and more effective agents. If a sulfonylurea must be used, glipizide is preferred.

Derm: photosensitivity, ERYTHEMA MULTIFORME, exfoliative dermatitis, rash.

Endo: hypoglycemia.

F and E: hyponatremia.

GI: constipation, cramps, diarrhea, dyspepsia, hepatitis, nausea, vomiting.

Hemat: agranulocytosis, APLASTIC ANEMIA, hemolytic anemia, leukopenia, pancytopenia, thrombocytopenia.

Metab: ↑appetite, ↑ weight.

Neuro: dizziness, drowsiness, headache, weakness.

Drug-Drug:

• ↑risk of elevated liver enzymes when used with bosentan; avoid concurrent use.
• Ingestion of alcohol may result in disulfiram-like reaction.
• Effectiveness may be ↓ by concurrent use of diuretics, corticosteroids, phenothiazines, oral contraceptives, estrogens, thyroid preparations, phenytoin, nicotinic acid, sympathomimetics, rifampin, and isoniazid.
• Alcohol, androgens (testosterone), chloramphenicol, ACE inhibitors, disopyramide, fluoxetine, clarithromycin, fluoroquinolones, MAO inhibitors, NSAIDs (except diclofenac), salicylates , and warfarin may ↑ the risk of hypoglycemia.
• Concurrent use with warfarin may alter the response to both agents (↑ effects of both initially, then ↓ activity); close monitoring recommended during any changes in dose.
• Beta-adrenergic blockers may mask the signs and symptoms of hypoglycemia.
• May ↑cyclosporine levels.
• Colesevelam may ↓ effects; administer glyburide 4 hr before colesevelam
• Topiramate may ↓ levels and ↓ effects

• PO (Adults): Non-micronized: 2.5–5 mg once daily initially (range 1.25–20 mg/day). Micronized: 1.5–3 mg/day initially (range 0.75–12 mg/day; doses >6 mg/day should be given as divided doses). Increments should not exceed 1.5 mg/wk.
• PO (Geriatric Patients): Nonmicronized: 1.25–2.5 mg/day initially; may be ↑ by 2.5 mg/day weekly. Micronized: 0.75–3 mg/day; may be ↑ by 1.5 mg/day weekly.

(Generic available)

• Nonmicronized tablets: 1.25 mg; 2.5 mg ; 5 mg;
• Micronized tablets (Glynase): 1.5 mg; 3 mg; 6 mg;
• In combination with: metformin.

• Observe for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety). Patients on concurrent beta-blocker therapy may have very subtle signs and symptoms of hypoglycemia.
• Assess patient for allergy to sulfonamides.

• Monitor serum glucose and glycosylated hemoglobin (HbA_1C) periodically during therapy to evaluate effectiveness.
  • Monitor CBC periodically during therapy. Report ↓ in blood counts promptly.
  • May cause an ↑ in AST, LDH, BUN, and serum creatinine.

• Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated with administration of oral glucose. Severe hypoglycemia should be treated with IV D50W followed by continuous IV infusion of more dilute dextrose solution at a rate sufficient to keep serum glucose at approximately 100 mg/dL.

• High Alert:Accidental administration of oral hypoglycemic agents to nondiabetic adults and children has resulted in serious harm or death.
• High Alert:Do not confuse glyburide with glipizide.
• Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
  • To convert from other oral hypoglycemic agents, gradual conversion is not required. For insulin dose of less than 20 units/day, change to glyburide can be made without gradual dose adjustment. Patients taking 20 or more units/day should convert gradually by receiving glyburide and a 25–30% reduction in insulin dose every day or every 2nd day with gradual insulin dose reduction as tolerated. Monitor serum or glucose and ketones at least 3 times/day during conversion.
• PO: May be administered once in the morning or divided into 2 doses. Administer with meals to ensure best diabetic control and to minimize gastric irritation. Do not administer after last meal of the day.
  • Nonmicronized glyburide should not be taken with a meal high in fat. Micronized glyburide cannot be substituted for nonmicronized glyburide. Preparations are not equivalent.

• Instruct patient to take medication at same time each day. Take missed doses as soon as remembered unless almost time for next dose. Do not take if unable to eat.
• Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
• Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to drink a glass of orange juice or ingest 2–3 tsp of sugar, honey, or corn syrup dissolved in water or an appropriate number of glucose tablets and notify health care professional.
• Concurrent use of alcohol may cause a disulfiram-like reaction (abdominal cramps, nausea, flushing, headaches, and hypoglycemia).
• Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
• Instruct patient in proper testing of serum glucose and ketones. Monitor closely during periods of stress or illness and health care professional notified if significant changes occur.
• May occasionally cause dizziness or drowsiness. Caution patient to avoid driving or other activities requiring alertness until response to medication is known.
• Caution patient to avoid other medications, especially aspirin and alcohol, while on this therapy without consulting health care professional.
• Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
• Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
• Advise patient to notify health care professional promptly if unusual weight gain, swelling of ankles, drowsiness, shortness of breath, muscle cramps, weakness, sore throat, rash, or unusual bleeding or bruising occurs.
• Insulin is the recommended method of controlling blood sugar during pregnancy. Counsel female patients to use a form of contraception other than oral contraceptives and to notify health care professional promptly if pregnancy is planned or suspected and to avoid breastfeeding. Discontinue glyburide at least 2 wk before expected delivery. Neonates of women with gestational diabetes who are treated with sulfonylureas during pregnancy may be at increased risk for respiratory distress and hypoglycemia (jitters, cyanosis, apnea, hypothermia, excessive sleepiness, poor feeding, seizures).
• Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
• Emphasize the importance of routine follow-up exams.

• Control of blood glucose levels without the appearance of hypoglycemic or hyperglycemic episodes.

DiaBeta, Glynase