QTERNMET XR(dapagliflozin, saxagliptin, and metforminhydrochloride)extended-release tablets(十四)
tion of Patients with at Least One Renal Impairment-Related AdverseReaction
Pool of 6 Placebo-Controlled
Studies (up to 104 weeks)*
Pool of 9 PlaceboControlled
Studies
(up to 104 weeks)†
Baseline Characteristics Placebo 5 mg
Dapagliflozin
10 mg
Dapagliflozin
Placebo 10 mg
Dapagliflozin
Overall population
Patients (%) with at least
one event
n=785
13 (1.7%)
n=767
14 (1.8%)
n=859
16 (1.9%)
n=1956
82 (4.2%)
n=2026
136 (6.7%)
65 years of age and older
Patients (%) with at least
one event
n=190
4 (2.1%)
n=162
5 (3.1%)
n=159
6 (3.8%)
n=655
52 (7.9%)
n=620
87 (14.0%)
eGFR ≥30‡ and
<60 mL/min/1.73 m2
Patients (%) with at least
one event
n=77
5 (6.5%)
n=88
7 (8.0%)
n=75
9 (12.0%)
n=249
40 (16.1%)
n=251
71 (28.3%)
65 years of age and older
and eGFR ≥30‡ and
<60 mL/min/1.73 m2
Patients (%) with at least
one event
n=41
2 (4.9%)
n=43
3 (7.0%)
n=35
4 (11.4%)
n=141
27 (19.1%)
n=134
47 (35.1%)
Subset of patients from the pool of 12 placebo-controlled studies with long-term extensions.
Subset of patients from the pool of 13 placebo-controlled studies with long-term extensions.
QTERNMET XR is contraindicated in patients with an eGFR less than 45 mL/min/1.73 m2.
In the pool of 12 clinical studies, a subgroup analysis assessed the safety of patients with eGFR between30 to less than 60 mL/min/1.73 m2At Week 24, the safety of dapagliflozin was similar to that seen in thedapagliflozin clinical program, although a higher proportion of patients had at least one event related to
renal impairment or failure. QTERNMET XR is contraindicated in patients with an eGFR<45 mL/min/1.73 m2.
Fractures
In a study of patients with eGFR 30 to less than 60 mL/min/1.73 m2, 13 patients experienced bonefractures for treatment durations up to 104 weeks. No fractures occurred in the placebo group, 5 occurredin the 5 mg dapagliflozin group, and 8 occurred in the 10 mg dapagliflozin group. Eight of these 13 fractures were in patients who had a baseline eGFR of 30 to 45 mL/min/1.73 m2
. QTERNMET XR is
contraindicated in patients with an eGFR <45 mL/min/1.73 m2
. Ten of the 13 fractures were reported
within the first 52 weeks. There was no apparent pattern with respect to the anatomic site of fracture.
Laboratory Findings
Decrease in Lymphocyte Counts
Saxagliptin
A dose-related mean decrease in absolute lymphocyte count has been observed with saxagliptin. In a poolof 5 placebo-controlled studies, a mean decrease in absolute lymphocyte count of approximately100 cells/microL relative to placebo was observed. The proportion of patients who were reported to havea lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, and 0.4% in the 2.5 mg, 5 mg saxagliptin andplacebo groups, respectively.
The clinical significance of this decrease in lymphocyte count relative to placebo is not known. The effectof saxagliptin on lymphocyte counts in patients with lymphocyte abnormalities (e.g., humanimmunodeficiency virus) is unknown.
Increase in Hematocrit
Dapagliflozin
In a pool of 13 placebo-controlled studies with dapagliflozin, increases from baseline in mean hematocritvalues were observed in dapagliflozin-treated patients starting at Week 1 and continuing up to Week 16,when the maximum mean difference from baseline was obse |
