Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP-4) inhibitor because it is unknown whether such patients will be predisposed to angioedema with saxagliptin.

5.9 Genital Mycotic Infections

Dapagliflozin increases the risks of genital mycotic infections. Patients with a history of genital mycotic infections were more likely to develop genital mycotic infections [see Adverse Reactions (6.1)]. Monitor and treat appropriately.

5.10 Increases in Low-Density Lipoprotein Cholesterol (LDL–C)

Increases in LDL–C can occur with dapagliflozin [see Adverse Reactions (6.1)]. Monitor LDL-C and treat per standard of care after initiating QTERN.

5.11 Bladder Cancer

Across 22 clinical studies for dapagliflozin, newly diagnosed cases of bladder cancer were reported in 10/6045 patients (0.17%) treated with dapagliflozin and 1/3512 patient (0.03%) treated with placebo/comparator. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 4 cases with dapagliflozin and no cases with placebo/comparator. Bladder cancer risk factors and hematuria (a potential indicator of pre-existing tumors) were balanced between treatment arms at baseline. There were too few cases to determine whether the emergence of these events is related to dapagliflozin.

There are insufficient data to determine whether dapagliflozin has an effect on pre-existing bladder tumors. Consequently, QTERN should not be used in patients with active bladder cancer. In patients with prior history of bladder cancer, the benefits of glycemic control versus unknown risks for cancer recurrence with QTERN should be considered.

5.12 Severe and Disabling Arthralgia

There have been postmarketing reports of severe and disabling arthralgia 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 of the medication. A subset of patients experienced a recurrence of symptoms restarting the same drug or a different DPP-4 inhibitor. Consider DPP-4 inhibitors as a possible cause for severe joint pain and discontinue drug if appropriate [see Adverse Reactions (6)].

5.13 Bullous Pemphigoid

Postmarketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving QTERN. If bullous pemphigoid is suspected, QTERN should be discontinued and referral to a dermatologist should be considered for diagnosis and appropriate treatment.

5.14 Macrovascular Outcomes

There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with QTERN.

6. ADVERSE REACTIONS 

The following important adverse reactions are described below or elsewhere in the labeling:

• Pancreatitis [see Warnings and Precautions (5.1)]

• Heart Failure [see Warnings and Precautions (5.2)]

• Hypotension [see Warnings and Precautions (5.3)]

• Ketoacidosis [see Warnings and Precautions (5.4)]

• Acute Kidney Injury an