KOMBIGLYZE XR (saxagliptin and metformin HCl extended-release) tablets contain two oral antihyperglycemic medications used in the management of type 2 diabetes mellitus: saxagliptin and metformin HCl. Saxagliptin Saxagliptin is an orally active inhibitor of the dipeptidyl-peptidase-4 (DPP4) enzyme. Saxagliptin monohydrate is described chemically as (1 S ,3 S ,5 S )-2-[(2 S )-2-Amino-2-(3-hydroxytricyclo[3.3.1. 13,7 ]dec-1-yl)acetyl]-2-azabicyclo[3.1.0]hexane-3-carbonitrile, monohydrate or (1 S ,3 ...

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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 ...

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Extended-Release Tablets: • 5 mg of saxagliptin and 500 mg of metformin HCl: light brown to brown, biconvex, capsule-shaped, film-coated tablets with “5/500” printed on one side and “4221” printed on the reverse side, in blue ink. • 5 mg of saxagliptin and 1,000 mg of metformin HCl: pink, biconvex, capsule-shaped, film-coated tablets with “5/1000” printed on one side and “4223” printed on the reverse side, in blue ink. • 2.5 mg of saxagliptin and 1,000 mg of metformin HCl: pale yellow to light yel...

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• Administer once daily with the evening meal. • Individualize the starting dosage based on the patient’s current regimen then adjust the dosage based on effectiveness and tolerability. • Do not exceed a daily dosage of 5 mg saxagliptin/2,000 mg metformin HCl extended-release. • Swallow whole. Never crush, cut, or chew. • Limit the saxagliptin dosage to 2.5 mg daily for patients also taking strong cytochrome P450 3A4/5 inhibitors (e.g., ketoconazole). ( 2.3 , 7.1) • Assess renal function prior to init...

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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. Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported [ see Warnings and Precautions and Adverse Reacti...

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Saxagliptin In a controlled clinical trial, once-daily, orally administered saxagliptin in healthy subjects at doses up to 400 mg daily for 2 weeks (80-times the MRHD) had no dose-related clinical adverse reactions and no clinically meaningful effect on QTc interval or heart rate. In the event of an overdose, initiate appropriate supportive treatment as dictated by the patient’s clinical status. Saxagliptin and its active metabolite are removed by hemodialysis (23% of dose over 4 hours). Contact t...

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• Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue KOMBIGLYZE XR. • 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. • Vitamin B 12 Deficiency: Metformin may lower vitamin B 12 levels. Measure hematological parameters annually. • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues: Consider a lo...

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• Strong CYP3A4/5 inhibitors (e.g., ketoconazole) : Coadministration with KOMBIGLYZE XR significantly increases saxagliptin concentrations. Limit KOMBIGLYZE XR dosage to 2.5 mg/1,000 mg once daily when coadministered with a strong CYP3A4/5 inhibitor. • Carbonic anhydrase inhibitors : May increase risk of lactic acidosis. Consider more frequent monitoring. • Drugs that reduce metformin clearance : May increase risk of lactic acidosis. Consider benefits and risks of concomitant use. • See full prescribi...

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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 pregnan...

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