Kombiglyze-XR 5 mg/1000 mg Tablets

Saxagliptin tablets are a dipeptidyl peptidase-4 (DPP-4) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. ( 1.1 ) Limitations of use: • Not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. ( 1.2 ) 1.1 Monotherapy and Combination Therapy Saxagliptin 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) ]. 1.2 Limitations of Use Saxagliptin tablets are not recommended for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.

• Recommended dosage is 2.5 mg or 5 mg orally once daily taken regardless of meals. • Patients with an eGFR < 45 mL/min/1.73 m 2 (moderate or severe renal impairment, or end-stage renal disease): Recommended dosage is 2.5 mg once daily regardless of meals. • Assess renal function before starting saxagliptin tablets and periodically thereafter. • Limit the dosage of saxagliptin tablets to 2.5 mg daily for patients also taking strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitors (e.g., ketoconazole)
• Recommended Dosage The recommended dosage of saxagliptin tablets is 2.5 mg or 5 mg orally once daily taken regardless of meals
• Do not cut, crush, or chew saxagliptin tablets
• If a dose is missed, advise patients not to take an extra dose
• Resume treatment with the next dose
• Dosage in Patients with Renal Impairment Assess renal function prior to initiation of saxagliptin tablets and then as clinically indicated [ see Use in Specific Populations ]
• The recommended dosage of saxagliptin tablets in patients with an eGFR greater than or equal to 45 mL/minute/1.73 m 2 is the same as the recommended dosage in patients with normal renal function [ see Dosage and Administration ]
• The dosage of saxagliptin tablets is 2.5 mg orally once daily for patients with eGFR < 45 mL/min/1.73 m 2 [which includes a subset of moderate or severe renal impairment, or with end-stage renal disease (ESRD) requiring hemodialysis] [ see Clinical Pharmacology and Clinical Studies ]. …

Saxagliptin Tablets are available containing 3.075 mg or 6.149 mg of saxagliptin hydrochloride dihydrate equivalent to 2.5 mg or 5 mg of saxagliptin. • The 2.5 mg tablets are yellow, film-coated, round, unscored tablets imprinted with SX1 over M in black ink on one side of the tablet and blank on the other side. …

• The safety and effectiveness of saxagliptin tablets as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus have not been established
• Pediatric patients
• Effectiveness of saxagliptin tablets was not demonstrated in a 26-week, placebo-controlled, double-blind randomized clinical trial with a 26-week safety extension (NCT03199053) in 164
• Pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus

In the seven, double-blind, controlled clinical safety and efficacy trials of saxagliptin tablets, a total of 4751 (42.0%) of the 11301 patients randomized to saxagliptin tablets were 65 years and over, and 1210 (10.7%) were 75 years and over. No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients. …

• Advise the patient to read the FDA-approved patient labeling (Medication Guide)
• Pancreatitis Inform patients that acute pancreatitis has been reported during postmarketing use of saxagliptin tablets
• Educate patients that persistent severe abdominal pain, sometimes radiating to the back, which may or may not be accompanied by vomiting, is the hallmark symptom of acute pancreatitis
• Instruct patients to promptly discontinue saxagliptin tablets and contact their health care provider if persistent severe abdominal pain occurs [ see Warnings and Precautions ]
• Heart Failure Inform patients of the signs and symptoms of heart failure. …

• Saxagliptin tablets are contraindicated in patients with a history of a serious hypersensitivity reaction to saxagliptin or any of the ingredients in saxagliptin tablets
• Reactions such as anaphylaxis, angioedema, or exfoliative skin conditions have been reported with saxagliptin tablets [ see Warnings and Precautions and Adverse Reactions ]. …

• Strong CYP3A4/5 inhibitors (e.g., ketoconazole): Coadministration with saxagliptin tablets significantly increases saxagliptin concentrations. Limit saxagliptin tablets dosage to 2.5 mg once daily when coadministered with a strong CYP3A4/5 inhibitor. ( 7.1 ) 7.1 Strong Inhibitors of CYP3A4/5 Enzymes Ketoconazole significantly increased saxagliptin exposure. Similar significant increases in plasma concentrations of saxagliptin are anticipated with other strong CYP3A4/5 inhibitors (e.g., atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin). …

• Pancreatitis: There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue saxagliptin tablets. ( 5.1 ) • Heart Failure: Consider the risks and benefits of saxagliptin tablets in patients who have known risk factors for heart failure. Monitor patients for signs and symptoms. ( 5.2 ) • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues: Consider a lower dosage of insulin or insulin secretagogue when used in combination with saxagliptin tablets. …

The following serious adverse reactions are described below or elsewhere in the prescribing information: • Pancreatitis [ see Warnings and Precautions (5.1) ] • Heart Failure [ see Warnings and Precautions (5.2) ] • Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues [ see Warnings and Precautions (5.3) ] • Hypersensitivity Reactions [ see Warnings and Precautions (5.4) ] • Severe and disabling arthralgia [ see Warnings and Precautions (5.5) ] • Bullous pemphigoid [ see Warnings and Precautions (5.6) ] • Most common adverse reactions (incidence ≥ 5% and more often than placebo) are upper respiratory tract infection, urinary tract infection, and headache. …

8.1 Pregnancy Risk Summary Limited data with saxagliptin tablets in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriages. There are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [ see Clinical Considerations ]. …

In a controlled clinical trial, once-daily, orally-administered saxagliptin tablets in healthy patients 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). …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.