Saxagliptin And Metformin Hydrochloride

1 INDICATIONS AND USAGE KOMBIGLYZE XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [ see Clinical Studies (14) ]. KOMBIGLYZE XR is a combination of saxagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, and metformin hydrochloride (HCl), a biguanide, indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. (1 ) Limitations of Use: • Not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. (1.1) 1.1 Limitations of Use KOMBIGLYZE XR is not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

6 ADVERSE REACTIONS The following serious adverse reactions are described below or elsewhere in the prescribing information: • Lactic Acidosis [ see Boxed Warning and Warnings and Precautions (5.1) ] • Pancreatitis [ see Warnings and Precautions (5.2) ] • Heart Failure [ see Warnings and Precautions (5.3) ] • Vitamin B 12 Concentrations [ see Warnings and Precautions (5.4) ] • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues [ see Warnings and Precautions (5.5) ] • Hypersensitivity Reactions [ see Warnings and Precautions (5.6) ] • Severe and disabling arthralgia [ see Warnings and Precautions (5.7) ] • Bullous pemphigoid [ see Warnings and Precautions (5.8) ] • Most common adverse reactions with metformin HCl extended-release (incidence >5% and more often than placebo...

8.1 Pregnancy Risk Summary Limited available data with KOMBIGLYZE XR or saxagliptin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects and miscarriage. Published trials with metformin use during pregnancy have not reported a clear association with metformin and major birth defect or miscarriage risk [ see Data ]. No adverse developmental effects independent of maternal toxicity were observed when saxagliptin and metformin were administered separately or in combination to pregnant rats and rabbits during the period of organogenesis [ see Data ].

WARNING: 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. 5 WARNINGS AND PRECAUTIONS • Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue KOMBIGLYZE XR. (5.2) • Heart Failure: Consider the risks and benefits of KOMBIGLYZE XR in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. ( 5.3 ) • Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually. ( 5.4 ) • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues: Consider a lower dosage of insulin or insulin secretagogue when used in combination with KOMBIGLYZE XR. 4 CONTRAINDICATIONS KOMBIGLYZE XR is contraindicated in patients with: • Severe renal impairment (eGFR below 30 mL/min/1.73 m2). • Acute or chronic metabolic acidosis, including diabetic ketoacidosis. Diabetic ketoacidosis should be treated with insulin. • A history of a serious hypersensitivity reaction to saxagliptin, metformin HCl, or any of the ingredients in KOMBLIGLYZE XR.