For: Diabetes Type 2
Qtern (dapagliflozin and saxagliptin) is a sodium-glucose cotransporter 2 (SGLT2) inhibitor and dipeptidyl peptidase-4 (DPP4) inhibitor fixed-dose combination for the treatment of adult patients with type 2 diabetes. IMPORTANT SAFETY INFORMATION for QTERN� (dapagliflozin and saxagliptin)
Prior serious hypersensitivity reaction to QTERN or its components
Moderate to severe renal impairment (eGFR <45 mL/min/1.73 m2), end-stage renal disease, or patients on dialysis
Warning and Precautions
Pancreatitis: There have been postmarketing reports of acute pancreatitis in patients taking saxagliptin, and in the SAVOR cardiovascular outcomes trial. Observe for pancreatitis. If pancreatitis is suspected, discontinue QTERN
Heart Failure: In the SAVOR cardiovascular outcomes trial, more patients treated with saxagliptin were hospitalized for heart failure compared to placebo. Patients with a prior history of heart failure or renal impairment had a higher risk for hospitalization for heart failure. Consider the risks and benefits of QTERN in patients who have known risk factors for heart failure. Monitor for signs and symptoms. If heart failure develops, consider discontinuation of QTERN.
Hypotension: Dapagliflozin causes intravascular volume contraction, and symptomatic hypotension can occur. Assess and correct volume status before initiating QTERN in patients with impaired renal function, elderly patients, or patients on loop diuretics. Do not initiate QTERN in patients with an eGFR <60 mL/min/1.73 m2. Monitor for hypotension
Ketoacidosis has been reported in patients with type 1 and type 2 diabetes receiving dapagliflozin. Some cases were fatal. Assess patients who present with signs and symptoms of metabolic acidosis for ketoacidosis, regardless of blood glucose level. If suspected, discontinue QTERN, evaluate and treat promptly. Before initiating QTERN, consider risk factors for ketoacidosis. Patients on QTERN may require monitoring and temporary discontinuation in situations known to predispose to ketoacidosis
Acute Kidney Injury and Impairment in Renal Function: Dapagliflozin causes intravascular volume contraction and renal impairment, with reports of acute kidney injury requiring hospitalization and dialysis. Consider temporarily discontinuing in settings of reduced oral intake or fluid losses. If acute kidney injury occurs, discontinue and promptly treat
Dapagliflozin increases serum creatinine and decreases eGFR. Elderly patients and patients with impaired renal function may be more susceptible to these changes. Before initiating QTERN, evaluate renal function and monitor periodically. Discontinue QTERN in patients if eGFR falls persistently below 60 mL/min/1.73 m2
Urosepsis and Pyelonephritis: SGLT2 inhibitors increase the risk for urinary tract infections (UTIs) and serious UTIs have been reported with dapagliflozin. Evaluate for signs and symptoms of UTIs and treat promptly
Hypoglycemia: QTERN can increase the risk of hypoglycemia when coadministered with insulin and insulin secretagogues. Consider lowering the dose of these agents when coadministered with QTERN
Hypersensitivity Reactions: Serious reactions have been reported in patients treated with saxagliptin, including anaphylaxis, angioedema, and exfoliative skin conditions. Onset of these reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with some reports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinue QTERN. Use caution in patients with a history of angioedema to another DPP-4 inhibitor.
Genital Mycotic Infections: Dapagliflozin increases the risk of genital mycotic infections, particularly in patients with prior genital mycotic infections. Monitor and treat appropriately
Increases in Low-Density Lipoprotein Cholesterol (LDL-C) occur with dapagliflozin. Monitor LDL-C and treat per standard of care
Bladder Cancer: An imbalance in bladder cancers was observed in clinical trials. There were too few cases to determine whether the emergence of these events is related to dapagliflozin, and insufficient data to determine whether dapagliflozin has an effect on pre-existing bladder tumors. QTERN should not be used in patients with active bladder cancer. Use with caution in patients with a history of bladder cancer
Severe and Disabling Arthralgia has been reported in patients taking DPP-4 inhibitors. The time to onset of symptoms following initiation of drug therapy varied from one day to years. Patients experienced relief of symptoms upon discontinuation. A subset of patients experienced a recurrence of symptoms when restarting the same drug or a different DPP-4 inhibitor. Consider discontinuing drug if appropriate.
Bullous Pemphigoid: There have been postmarketing reports of bullous pemphigoid requiring hospitalization in patients taking DPP-4 inhibitors. Tell patients to report development of blisters or erosions. If suspected, discontinue QTERN
Macrovascular Outcomes: There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with QTERN
Most common adverse reactions reported in ≥5% of patients treated with 10 mg dapagliflozin and 5 mg saxagliptin were upper respiratory tract infection (13.6%), urinary tract infection (5.7%), and dyslipidemia (5.1%).
Strong CYP3A4/5 inhibitors (eg, ketoconazole): Coadministration with QTERN significantly increases saxagliptin concentrations. Do not coadminister QTERN.
Use in Specific Populations
Pregnancy: Advise females of the potential risk to a fetus especially during the second and third trimesters
Lactation: QTERN is not recommended when breastfeeding
INDICATION AND LIMITATIONS OF USE for QTERN� (dapagliflozin and saxagliptin)
QTERN is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus (T2DM) who have inadequate control with dapagliflozin or who are already treated with dapagliflozin and saxagliptin.
QTERN is not indicated for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. QTERN should only be used in patients who tolerate 10 mg dapagliflozin.
Please see accompanying US Full Prescribing Information for QTERN.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088.