Glipizide: uses, appearance and warnings

GLUCOTROL XL is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. GLUCOTROL XL is a sulfonylurea indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus Limitations of Use: Not for treatment of type 1 diabetes or diabetic ketoacidosis 1.1 Limitations of Use GLUCOTROL XL is not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

GLUCOTROL XL (glipizide) Extended Release tablets: 2.5 mg, blue and imprinted with "GLUCOTROL XL 2.5" or "GXL 2.5" on one side 5 mg, white and imprinted with "GLUCOTROL XL 5" or "GXL 5" on one side 10 mg, white and imprinted with "GLUCOTROL XL 10" or "GXL 10" on one side Tablets: 2.5 mg, 5 mg, 10 mg ( 3 ).

GLUCOTROL XL (glipizide) Extended Release Tablets are supplied to provide 2.5 mg, 5 mg, and 10 mg round, biconvex tablets and imprinted with black ink as follows: Table 2. GLUCOTROL XL Tablet Presentations Tablet Strength Tablet Color/Shape Tablet Markings Package Size NDC Code 2.5 mg Blue Round Biconvex imprinted with "GXL 2.5" on one side Bottles of 30 NDC 0049-0170-01 5 mg White Round Biconvex imprinted with "GXL 5" on one side Bottles of 100 Bottles of 500 NDC 0049-0174-02 NDC 0049-0174-03 10 mg White Round Biconvex imprinted with "GXL 10" on one side Bottles of 100 Bottles of 500 NDC 0049-0178-07 NDC 0049-0178-08 Recommended Storage: The tablets should be protected from moisture and humidity. Store at 68–77°F (20–25°C); excursions permitted between 59°F and 86°F (15°C and 30°C) [see USP Controlled Room Temperature].

Glipizide is contraindicated in patients with: • Known hypersensitivity to glipizide or any of the product's ingredients. • Hypersensitivity to sulfonamide derivatives. ▪ Known hypersensitivity to glipizide or any of the product's ingredients ( 4 ). ▪ Hypersensitivity to sulfonamide derivatives ( 4 ).

▪ Hypoglycemia: May be severe. Ensure proper patient selection, dosing, and instructions, particularly in at-risk populations (e.g., elderly, renally impaired) and when used with other anti-diabetic medications ( 5.1 ). ▪ Hemolytic Anemia: Can occur if glucose 6-phosphate dehydrogenase (G6PD) deficient. Consider a non-sulfonylurea alternative ( 5.2 ). ▪ Potential Increased Risk of Cardiovascular Mortality with Sulfonylureas: Inform patient of risks, benefits and treatment alternatives ( 5.3 ). ▪ Macrovascular Outcomes: No clinical studies have established conclusive evidence of macrovascular risk reduction with GLUCOTROL XL or any other anti-diabetic drug ( 5.4 ). 5.1 Hypoglycemia All sulfonylurea drugs, including GLUCOTROL XL, are capable of producing severe hypoglycemia [see Adverse Reactions (6) ] . Concomitant use of GLUCOTROL XL with other anti-diabetic medication can increase the risk of hypoglycemia. A lower dose of GLUCOTROL XL may be required to minimize the risk of hypoglycemia when combining it with other anti-diabetic medications. Educate patients to recognize and manage hypoglycemia. When initiating and increasing GLUCOTROL XL in patients who may be predisposed to hypoglycemia (e.g., the elderly, patients with renal impairment, patients on other anti-diabetic medications) start at 2.5 mg. Debilitated or malnourished patients, and those with adrenal, pituitary, or hepatic impairment are particularly susceptible to the hypoglycemic action of anti-diabetic medications. Hypoglycemia is also more likely to occur when caloric intake is deficient, after severe or prolonged exercise, or when alcohol is ingested. The patient's ability to concentrate and react may be impaired as a result of hypoglycemia. Early warning symptoms of hypoglycemia may be different or less pronounced in patients with autonomic neuropathy, the elderly, and in patients who are taking beta-adrenergic blocking medications or other sympatholytic agents. These situations may result in severe hypoglycemia before the patient is aware of the hypoglycemia . These impairments may present a risk in situations where these abilities are especially important, such as driving or operating other machinery. Severe hypoglycemia can lead to unconsciousness or convulsions and may result in temporary or permanent impairment of brain function or death. 5.2 Hemolytic Anemia Treatment of patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency with sulfonylurea agents, including GLUCOTROL XL, can lead to hemolytic anemia. Avoid use of GLUCOTROL XL in patients with G6PD deficiency. In post marketing reports, hemolytic anemia has also been reported in patients who did not have known G6PD deficiency. 5.3 Increased Risk of Cardiovascular Mortality with Sulfonylureas The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with type 2 diabetes mellitus. The study involved 823 patients who were randomly assigned to one of four treatment groups. UGDP reported that patients treated for 5 to 8 years with diet plus a fixed dose of tolbutamide (1.5 grams per day) had a rate of cardiovascular mortality approximately 2½ times that of patients treated with diet alone. A significant increase in total mortality was not observed, but the use of tolbutamide was discontinued based on the increase in cardiovascular mortality, thus limiting the opportunity for the study to show an increase in overall mortality. Despite controversy regarding the interpretation of these results, the findings of the UGDP study provide an adequate basis for this warning. The patient should be informed of the potential risks and advantages of glipizide and of alternative modes of therapy. Although only one drug in the sulfonylurea class (tolbutamide) was included in this study, it is prudent from a safety standpoint to consider that this warning may also apply to other oral hypoglycemic drugs in this class, in view of their close similarities in mode of action and chemical structure. 5.4 Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with GLUCOTROL XL or any other anti-diabetic drug. 5.5 Gastrointestinal Obstruction There have been reports of obstructive symptoms in patients with known strictures in association with the ingestion of another drug with this non-dissolvable extended release formulation. Avoid use of GLUCOTROL XL in patients with preexisting severe gastrointestinal narrowing (pathologic or iatrogenic).

The following serious adverse reactions are discussed in more detail below and elsewhere in the labeling: • Hypoglycemia [see Warnings and Precautions (5.1) ] • Hemolytic anemia [see Warnings and Precautions (5.2) ] Most common adverse reactions (incidence > 3%) are dizziness, diarrhea, nervousness, tremor, hypoglycemia and flatulence ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Pfizer, Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. …

▪ Certain medications may affect glucose metabolism, requiring GLUCOTROL XL dose adjustment and close monitoring of blood glucose ( 7.1 ). ▪ Miconazole: Monitor patients closely. Severe hypoglycemia can occur when GLUCOTROL and oral miconazole are used concomitantly ( 7.2 , 12.3 ). ▪ Fluconazole: Monitor patients closely. An increase in GLUCOTROL AUC was seen after fluconazole administration ( 7.3 , 12.3 ). ▪ Colesevelam: GLUCOTROL XL should be administered at least 4 hours prior to colesevelam ( 7.4 , 12.3 ). 7.1 Drugs Affecting Glucose Metabolism A number of medications affect glucose metabolism and may require GLUCOTROL XL dose adjustment and close monitoring for hypoglycemia or worsening glycemic control. …