Saxagliptin (2 brand names, 2 dosage forms, 1 route)
Available dosage forms: TABLET, TABLET, EXTENDED RELEASE.
Routes of administration: ORAL.
Brand Names
- SAXAGLIPTIN
- SAXAGLIPTIN;METFORMIN HYDROCHLORIDE
Boxed Warning
• 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 Warnings and Precautions (5.1) ]. • 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 diseases [see Warnings and Precautions (5.1) ]. • Steps to reduce the risk of and manage metformin-associated lactic acidosis in these high risk groups are provided in the full prescribing information [see Dosage and Administration (2.2), Contraindications (4), Warnings and Precautions (5.1), Drug Interactions (7), and Use in Specific Populations (8.6, 8.7) ]. • If metformin-associated lactic acidosis is suspected, immediately discontinue saxagliptin and metformin hydrochloride extended-release tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended [see Warnings and Precautions (5.1) ].
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) ].
Contraindications
Saxagliptin and metformin hydrochloride extended-release tablets are 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 saxagliptin and metformin hydrochloride extended-release tablets. Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported [see Warnings and Precautions (5.6) and Adverse Reactions (6.2) ].
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 B12 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) ]
Drug Interactions
The concomitant use of saxagliptin and metformin hydrochloride extended-release tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance or increase metformin accumulation [see Drug Interactions (7) ]. Therefore, consider more frequent monitoring of patients.
Overdosage
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 the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations. Metformin HCl Overdose of metformin HCl has occurred, including ingestion of amounts greater than 50 grams. Hypoglycemia was reported in approximately 10% of cases, but no causal association with metformin HCl has been established. Lactic acidosis has been reported in approximately 32% of metformin overdose cases [see Warnings and Precautions (5.1) ]. Metformin is dialyzable with a clearance of up to 170 mL/min under good hemodynamic conditions. Therefore, hemodialysis may be useful for removal of accumulated drug from patients in whom metformin overdosage is suspected.