No

Antidiabetic Agent (Sulfonylurea)

Management of noninsulin-dependent diabetes mellitus (type 2)

C

Clinical effects on the fetus: Crosses the placenta. Insulin is the drug of choice for the control of diabetes mellitus during pregnancy.

Breast-feeding/lactation: No data available

Hypersensitivity to glipizide or any component, other sulfonamides, type 1 diabetes mellitus

Use with caution in patients with severe hepatic disease; a useful agent since few drug to drug interactions and not dependent upon renal elimination of active drug

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).

>10%:

Central nervous system: Headache

Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, epigastric fullness, constipation, heartburn

1% to 10%: Dermatologic: Rash, urticaria, photosensitivity

<1%: Edema, hypoglycemia, hyponatremia, blood dyscrasias, aplastic anemia, hemolytic anemia, bone marrow suppression, thrombocytopenia, agranulocytosis, cholestatic jaundice, diuretic effect

Symptoms of overdose include low blood sugar, 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)

Decreased effects: Beta-blockers, cholestyramine, hydantoins, rifampin, thiazide diuretics, urinary alkalines, charcoal

Increased effects: H₂-antagonists, anticoagulants, androgens, fluconazole, salicylates, gemfibrozil, sulfonamides, tricyclic antidepressants, probenecid, MAO inhibitors, methyldopa, digitalis glycosides, urinary acidifiers

Increased toxicity: Cimetidine may increase hypoglycemic effects

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

Peak blood glucose reductions: Within 1.5-2 hours

Duration of action: 12-24 hours

Protein binding: 92% to 99%

Absorption: Delayed when given with food

Metabolism: In the liver with metabolites (91% to 97%)

Half-life: 2-4 hours

Elimination: Metabolites (91% to 97%) excreted in urine (60% to 80%) and feces (11%)

Oral (allow several days between dose titrations): Give ~30 minutes before a meal to obtain the greatest reduction in postprandial hyperglycemia

Elderly: Initial: 2.5 mg/day; increase by 2.5-5 mg/day at 1- to 2-week intervals

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 <10 mL/minute: Some investigators recommend not using

Dosing adjustment in hepatic impairment: Initial dosage should be 2.5 mg/day

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

Food: Food delays absorption by 40%; take glipizide before meals

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.

Urine for glucose and ketones; monitor for signs and symptoms of hypoglycemia (fatigue, excessive hunger, profuse sweating, numbness of extremities), fasting blood glucose, hemoglobin A_1c, fructosamine

Target range: Adults:

Glycosylated hemoglobin: <7%

None reported

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

No information available to require special precautions

Glipizide-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 chew or crush extended release tablets. 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, diarrhea, or constipation; 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 NPO may need to have their dose held to avoid hypoglycemia

Tablet: 5 mg, 10 mg

Tablet, extended release: 5 mg, 10 mg

Berelowitz M, Fischette C, Cefalu W, et al, "Comparative Efficacy of a Once-Daily Controlled-Release Formulation of Glipizide and Immediate-Release Glipizide in Patients With NIDDM," Diabetes Care, 1994, 17(12):1460-4.

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

Kilo C, Meenan A, and Bloomgarden Z, "Glyburide Versus Glipizide in the Treatment of Patients With Noninsulin-Dependent Diabetes Mellitus," Clin Ther, 1992, 14(6):801-12.

Kradjan WA, Kobayashi KA, Bauer LA, et al, "Glipizide Pharmacokinetics: Effects of Age, Diabetes, and Multiple Dosing," J Clin Pharmacol, 1989, 29(12):1121-7.

Kradjan WA, Takeuchi KY, Opheim KE, et al, "Pharmacokinetics and Pharmacodynamics of Glipizide After Once-Daily and Divided Doses," Pharmacotherapy, 1995, 15(4):465-71.

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.

"Standards of Medical Care for Patients With Diabetes Mellitus. American Diabetes Association," Diabetes Care, 1994, 17(6):616-23.