QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(十)
ernative therapy for glycemic control.
5.10 Hypersensitivity Reactions
There have been postmarketing reports of serious hypersensitivity reactions in patients treated withsaxagliptin. These reactions include anaphylaxis, angioedema and exfoliative skin conditions. Onset ofthese reactions occurred within the first 3 months after initiation of treatment with saxagliptin, with somereports occurring after the first dose. If a serious hypersensitivity reaction is suspected, discontinueQTERNMET XR, treat per standard of care, and monitor until signs and symptoms are resolved. Assessfor other potential causes for the event. Institute alternative treatment for diabetes.
Use caution in a patient with a history of angioedema to another dipeptidyl peptidase-4 (DPP-4) inhibitorbecause it is unknown whether such patients will be predisposed to angioedema with saxagliptin.
5.11 Vitamin B12 Concentrations
In controlled clinical trials of metformin of 29-week duration, a decrease to subnormal levels ofpreviously normal serum vitamin B12 levels, without clinical manifestations, was observed inapproximately 7% of patients. This decrease, possibly due to interference with B12 absorption from theB12-intrinsic factor complex is, however, very rarely associated with anemia and appears to be rapidlyreversible with discontinuation of metformin or vitamin B12 supplementation. Measurement of
hematologic parameters on an annual basis is advised in patients on QTERNMET XR and any apparentabnormalities should be appropriately investigated and managed.
Certain individuals (those with inadequate vitamin B12 or calcium intake or absorption) appear to bepredisposed to developing subnormal vitamin B12 levels. In these patients, routine serum vitamin B12measurements at 2- to 3-year intervals may be useful.
5.12 Genital Mycotic Infections
Dapagliflozin increases the risks of genital mycotic infections. Patients with a history of genital mycoticinfections were more likely to develop genital mycotic infections [see ADVERSE REACTIONS (6.1)].
Monitor and treat appropriately.
5.13 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 QTERNMET XR.
5.14 Bladder Cancer
Across 22 clinical studies for dapagliflozin, newly diagnosed cases of bladder cancer were reported in10/6045 patients (0.17%) treated with dapagliflozin and 1/3512 patient (0.03%) treated withplacebo/comparator. After excluding patients in whom exposure to study drug was less than one year atthe time of diagnosis of bladder cancer, there were 4 cases with dapagliflozin and no cases withplacebo/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 determinewhether the emergence of these events is related to dapagliflozin.
There are insufficient data to determine whether dapagliflozin has an effect on pre-existing bladdertumors. Consequently, QTERNMET XR should not be used in patients with active bladder cancer. Inpatients with prior history of bladder cancer, the benefits of glycemic control versus unknown risks forcancer recurrence with QTERNMET XR should be considered.
5.15 Severe and Disabling Arthralgia
There have been postmarketing reports of seve |
