glipizide
Glucotrol, Glucotrol XL

Available forms
Available by prescription only
Tablets: 5 mg, 10 mg
Tablets (extended-release): 2.5 mg, 5 mg, 10 mg

Indications and dosages
 Adjunct to diet to lower blood glucose levels in patients with non-insulin-dependent (type 2) diabetes mellitus. Tablets. Adults: Initially, 5 mg P.O. daily 30 minutes before breakfast. Adjust dose in increments of 2.5 to 5 mg. Usual maintenance dose is 10 to 15 mg daily. Maximum recommended daily dose is 40 mg. Divide total daily doses of more than 15 mg except when using extended-release tablets.
≡ Dosage adjustment. Initial dose in elderly patients or those with hepatic disease may be 2.5 mg P.O. daily.
Extended-release tablets
Adults: Initially, 5 mg P.O. daily. May increase to 10 mg after 3 months based on glycosylated hemoglobin measurement. Subsequent dose adjustments should be based on glycosylated hemoglobin measurements at 3-month intervals. If no response after 3 months on higher dose, previous dose should be resumed. Maximum daily dose is 20 mg.
 To replace insulin therapy. Adults: If insulin dose is more than 20 units daily, patient may be started at usual dose of glipizide (5 mg daily) plus 50% of insulin dosage. If insulin dose is less than 20 units, insulin may be discontinued.

Pharmacodynamics
Antidiabetic action: Glipizide decreases blood glucose levels by stimulating insulin release from functioning beta cells in the pancreas. After prolonged administration, hypoglycemic effects of drug appear to reflect extrapancreatic effects, possibly including reduction of basal hepatic glucose production and enhanced peripheral sensitivity to insulin.

Pharmacokinetics
Absorption: Absorbed rapidly and completely from the GI tract.
Distribution: Probably distributed in the extracellular fluid. Drug is about 92% to 99% protein-bound.
Metabolism: Metabolized almost completely by the liver to inactive metabolites.
Excretion: Excreted primarily in urine; small amounts are excreted in feces. Renal clearance of unchanged glipizide increases with increasing urinary pH. Duration of action is 10 to 24 hours; half-life is 2 to 4 hours.

Contraindications and precautions
Contraindicated in pregnant and breast-feeding women, patients hypersensitive to drug, and patients with diabetic ketoacidosis with or without coma. Also contraindicated as sole therapy for type 2 diabetes complicated by acidosis, ketosis, or coma.
  Use cautiously in patients with impaired renal or hepatic function and in geriatric, malnourished, or debilitated patients.

Interactions
Drug-drug. Adrenocorticoids, amphetamines, baclofen, corticotropin, epinephrine, estrogens, ethacrynic acid, furosemide, glucocorticoids, hormonal contraceptives, phenytoin, thiazide diuretics, thyroid hormones, triamterene: May increase glucose levels. Dosage adjustments may be required.
Anabolic steroids, chloramphenicol, clofibrate, guanethidine, insulin, MAO inhibitors, probenecid, salicylates, sulfonamides: Enhances hypoglycemic effect from displacement of glipizide from protein-binding sites. Monitor patient.
Antifungal antibiotics such as fluconazole, miconazole: Increases glipizide levels and hypoglycemia. Monitor patient.
Beta blockers, including ophthalmics: May mask symptoms of hypoglycemia. Monitor patient closely.
Cimetidine: Potentiates hypoglycemic effects through prevention of hepatic metabolism. Monitor patient closely.
Corticosteroids, glucagon, rifampin, thiazide diuretics: May decrease hypoglycemic response. Monitor patient closely.
Hydantoins: Increases hydantoin levels. Monitor blood levels.
Drug-food. Any food: Delays absorption. Tell patient to take drug 30 minutes before meals.
Drug-lifestyle. Alcohol use: Alters glycemic control. May also cause a disulfiram-like reaction. Discourage alcohol use.
Smoking: Increases corticosteroid release, requiring higher dosages. Discourage smoking.

Adverse reactions
CNS: asthenia, dizziness, drowsiness, headache, pain, tremor, nervousness, insomnia, anxiety, depression, hypesthesia, paresthesia.
GI: nausea, constipation, diarrhea, flatulence, dyspepsia, vomiting.
Hematologic: leukopenia, hemolytic anemia, agranulocytosis, thrombocytopenia, aplastic anemia.
Hepatic: cholestatic jaundice.
Metabolic: altered cholesterol level, hypoglycemia.
Skin: rash, pruritus.
Other: SIADH.

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

Overdose and treatment
Signs and symptoms include low blood glucose levels, tingling of lips and tongue, hunger, nausea, decreased cerebral function, increased sympathetic activity, and, ultimately, seizures, stupor, and coma.
 Mild hypoglycemia responds to treatment with oral glucose and dosage adjustments. If patient loses consciousness or experiences other neurologic changes, he should receive a rapid injection of dextrose 50%, followed by continuous infusion of dextrose 10% at a rate to maintain blood glucose levels more than 100 mg/dl. Monitor patient for 24 to 48 hours.

Special considerations
• To improve glucose control in patients who receive 15 mg/day or more, doses can be divided and given 30 minutes before the morning and evening meals.
• Some patients taking glipizide can control their glucose levels with a once-daily regimen; others show better response with divided doses.
• Drug has a mild diuretic effect that may be useful in patients with heart failure or cirrhosis.
• Patients who may be more sensitive to drug, such as elderly, debilitated, or malnourished patients, should begin therapy with lower doses (2.5 mg once daily).
• Oral antidiabetics may increase the risk of CV mortality as compared with diet or diet and insulin therapy.
• When substituting glipizide for chlorpropamide, monitor patient carefully during the first week because of the prolonged retention of chlorpropamide.
• Monitor blood glucose, urine glucose, ketone, and glycosylated hemoglobin levels.
Pregnant patients
• Use in pregnancy usually isn’t recommended. If glipizide must be used, manufacturer recommends stopping drug at least 1 month before expected delivery to prevent neonatal hypoglycemia.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• These patients may be more sensitive to drug effects.
• Hypoglycemia causes increased neurologic symptoms in elderly patients.

Patient education
• Emphasize the importance of following prescribed diet, exercise, and medical regimen.
• Tell patient that, if a dose is missed, it should be taken immediately, unless it’s almost time to take the next dose. Patient shouldn’t double the dose.
• Advise patient to avoid alcohol and products containing alcohol when taking glipizide.
• Suggest that drug be taken with food if glipizide causes GI upset.
• Teach patient how to monitor blood glucose, urine glucose, and ketone levels, as needed.
• Teach patient how to recognize and manage hyperglycemia and hypoglycemia.
• Tell patient not to crush or divide extended-release tablets.

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