Overview
11 DESCRIPTION Saxagliptin and metformin hydrochloride 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.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Saxagliptin and Metformin Hydrochloride Extended-release Tablets Saxagliptin and metformin hydrochloride extended-release tablets contains two antihyperglycemic medications: saxagliptin, a dipeptidyl-peptidase-4 (DPP4) inhibitor, and metformin HCl, a biguanide. Saxagliptin Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP4 enzyme within minutes.
Indications
- 1 INDICATIONS AND USAGE Saxagliptin and metformin hydrochloride extended-release tablets are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus [see Clinical Studies ( 14 )]. Saxagliptin and metformin hydrochloride extended-release tablets are 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.
Common Doses
- 5 mg
- 000 mg
- 2.5 mg
- 30 mL
Dosage
2 DOSAGE AND ADMINISTRATION Administer once daily with the evening meal. ( 2.1 ) Individualize the starting dosage based on the patient’s current regimen then adjust the dosage based on effectiveness and tolerability. ( 2.1 ) Do not exceed a daily dosage of 5 mg saxagliptin/2,000 mg metformin HCl extended-release. ( 2.1 ) Swallow whole. Never crush, cut, or chew. ( 2.1 ) 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.
Black Box Warning
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. 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...
Contraindications
- 4 CONTRAINDICATIONS Saxagliptin and metformin hydrochloride extended-release tablets are contraindicated in patients with: Severe renal impairment (eGFR below 30 mL/min/1.73 m 2 ). 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 saxagliptin and metformin hydrochloride extended-release tablets.
Side Effects
- 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.
Interactions
- 7 DRUG INTERACTIONS Strong CYP3A4/5 inhibitors (e.g., ketoconazole) : Coadministration with saxagliptin and metformin hydrochloride extended-release tablets significantly increases saxagliptin concentrations. Limit saxagliptin and metformin hydrochloride extended-release tablets dosage to 2.5 mg/1,000 mg once daily when coadministered with a strong CYP3A4/5 inhibitor. ( 2.3 , 7.1 ) Carbonic anhydrase inhibitors: May increase risk of lactic acidosis. Consider more frequent monitoring. ( 7.2 ) Drugs that reduce metformin clearance: May increase risk of lactic acidosis.