Glipizide and metformin: uses, appearance and warnings

Glipizide and metformin hydrochloride tablets, USP are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Glipizide and Metformin Hydrochloride Tablets USP, 2.5 mg/250 mg are pink-colored, biconvex, modified capsule-shaped, film-coated tablet, debossed with "ZE68" on one side and plain on other side and are supplied as follows: NDC 68382-184-16 in bottle of 90 tablets with child-resistant closure NDC 68382-184-01 in bottle of 100 tablets NDC 68382-184-10 in bottle of 1000 tablets NDC 68382-184-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Glipizide and Metformin Hydrochloride Tablets USP, 2.5 mg/500 mg are white-colored, biconvex, modified capsule-shaped, film-coated tablet, debossed with "ZE67" on one side and plain on other side and are supplied as follows: NDC 68382-185-16 in bottle of 90 tablets with child-resistant closure NDC 68382-185-01 in bottle of 100 tablets NDC 68382-185-10 in bottle of 1000 tablets NDC 68382-185-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Glipizide and Metformin Hydrochloride Tablets USP, 5 mg/500 mg are pink-colored, biconvex, modified capsule-shaped, film-coated tablet, debossed with "ZE66" on one side and plain on other side and are supplied as follows: NDC 68382-186-16 in bottle of 90 tablets with child-resistant closure NDC 68382-186-01 in bottle of 100 tablets NDC 68382-186-10 in bottle of 1000 tablets NDC 68382-186-77 in unit-dose blister cartons of 100 (10 x 10) unit-dose tablets Storage: Store at 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight container.

Glipizide and metformin hydrochloride tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mlL/min/1.73 m 2 ) (see WARNINGS and PRECAUTIONS ). Known hypersensitivity to glipizide or metformin hydrochloride. Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. Diabetic ketoacidosis should be treated with insulin. WARNINGS SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY 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 non-insulin-dependent diabetes. The study involved 823 patients who were randomly assigned to 1 of 4 treatment groups ( Diabetes 19 (Suppl. 2):747-830, 1970). UGDP reported that patients treated for 5 years 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 benefits of glipizide and of alternative modes of therapy. …

LACTIC ACIDOSIS Post-marketing cases of metformin-associated lactic acidosis have resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias. The onset of metformin-associated lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, somnolence, and abdominal pain. Metformin-associated lactic acidosis was characterized by elevated blood lactate levels (> 5 mmol/Liter), anion gap acidosis (without evidence of ketonuria or ketonemia), an increased lactate/pyruvate ratio; and metformin plasma levels generally > 5 mcg/mL [see PRECAUTIONS ] Risk factors for metformin-associated lactic acidosis include renal impairment, concomitant use of certain drugs (e.g., carbonic anhydrase inhibitors such as topiramate), age 65 years old or greater, having a radiological study with contrast, surgery and other procedures, hypoxic states (e.g., acute congestive heart failure), excessive alcohol intake, hepatic impairment, and mitochondrial disease. Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided [see PRECAUTIONS ]. If metformin-associated lactic acidosis is suspected, immediately discontinue glipizide and metformin hydrochloride and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see PRECAUTIONS ].

Glipizide and Metformin Hydrochloride Tablets: In a double-blind 24 week clinical trial involving glipizide and metformin hydrochloride tablets as initial therapy, a total of 172 patients received glipizide and metformin hydrochloride tablets, 2.5 mg/250 mg, 173 received glipizide and metformin hydrochloride tablets, 2.5 mg/500 mg, 170 received glipizide, and 177 received metformin. The most common clinical adverse events in these treatment groups are listed in Table 4 . …