Glipizide

Product labeling states oral hypoglycemic drugs may be associated with an increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin. Data to support this association are limited, and several studies, including a large prospective trial (UKPDS) have not supported an association.

All sulfonylurea drugs are capable of producing severe hypoglycemia. Hypoglycemia is more likely to occur when caloric intake is deficient, after severe or prolonged exercise, when ethanol is ingested, or when more than one glucose-lowering drug is used. It is also more likely in elderly or debilitated patients, malnourished patients and in patients with impaired renal or hepatic function, adrenal and/or pituitary insufficiency; use with caution. Autonomic neuropathy, advanced age, and concomitant use of beta-blockers or other sympatholytic agents may impair the patient's ability to recognize the signs and symptoms of hypoglycemia; use with caution.

The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes. Disease-related concerns:

Patients with G6PD deficiency may be at an increased risk of sulfonylurea-induced hemolytic anemia; however, cases have also been described in patients without G6PD deficiency during postmarketing surveillance. Use with caution and consider a nonsulfonylurea alternative in patients with G6PD deficiency.

Use with caution in patients with hepatic impairment; hypoglycemia may be prolonged.

Use with caution in patients with renal impairment.

It may be necessary to discontinue therapy and administer insulin if the patient is exposed to stress (fever, trauma, infection, surgery). Dosage form specific issues:

The extended release formulation consists of drug within a nondeformable matrix; following drug release/absorption, the matrix/shell is expelled in the stool. The use of nondeformable products in patients with known stricture/narrowing of the GI tract has been associated with symptoms of obstruction. Avoid use of extended release tablets (Glucotrol XL) in patients with severe gastrointestinal narrowing or esophageal dysmotility. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:

Use with caution; dosing should be conservative and monitor closely for hypoglycemia.

Use with caution; dosing should be conservative and monitor closely for hypoglycemia. Sulfonylureas of shorter duration (eg, glipizide) are preferred in elderly patients (ADA 2018b). Other warnings/precautions:

Not for use in patients with diabetic ketoacidosis (DKA) or patients with type 1 diabetes mellitus.