SYNJARDYXR(empagliflozin and metformin hydrochloride extended-release) tablets(十一)
is, which may lead to intravascular volume contraction and adverse reactions related to volume depletion. In the pool of five placebo-controlled clinical trials, adverse reactions related to volume depletion (e.g., blood pressure (ambulatory) decreased, blood pressure systolic decreased, dehydration, hypotension, hypovolemia, orthostatic hypotension, and syncope) were reported by 0.3%, 0.5%, and 0.3% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively. Empagliflozin may increase the risk of hypotension in patients at risk for volume contraction [see WARNINGS AND PRECAUTIONS (5.2) and USE IN SPECIFIC POPULATIONS (8.5, 8.6)].
Increased Urination
In the pool of five placebo-controlled clinical trials, adverse reactions of increased urination (e.g., polyuria, pollakiuria, and nocturia) occurred more frequently on empagliflozin than on placebo (see Table 3). Specifically, nocturia was reported by 0.4%, 0.3%, and 0.8% of patients treated with placebo, empagliflozin 10 mg, and empagliflozin 25 mg, respectively.
Acute Impairment in Renal Function
Treatment with empagliflozin was associated with increases in serum creatinine and decreases in eGFR (see Table 3). Patients with moderate renal impairment at baseline had larger mean changes [see WARNINGS AND PRECAUTIONS (5.4) and USE IN SPECIFIC POPULATIONS (8.5, 8.6)].
In a long-term cardiovascular outcome trial, the acute impairment in renal function was observed to reverse after treatment discontinuation suggesting acute hemodynamic changes play a role in the renal function changes observed with empagliflozin.
Table 3 Changes from Baseline in Serum Creatinine and eGFRa in the Pool of Four 24-week Placebo-Controlled Studies and Renal Impairment Study
aObserved cases on treatment.
bSubset of patients from renal impairment study with eGFR 30 to less than 60 mL/min/1.73 m2.
cApproximately 3 weeks after end of treatment.
Pool of 24-Week Placebo-Controlled Studies
Placebo Empagliflozin
10 mg Empagliflozin
25 mg
Baseline Mean N 825 830 822
Creatinine (mg/dL) 0.84 0.85 0.85
eGFR (mL/min/1.73 m2) 87.3 87.1 87.8
Week 12 Change N 771 797 783
Creatinine (mg/dL) 0.00 0.02 0.01
eGFR (mL/min/1.73 m2) -0.3 -1.3 -1.4
Week 24 Change N 708 769 754
Creatinine (mg/dL) 0.00 0.01 0.01
eGFR (mL/min/1.73 m2) -0.3 -0.6 -1.4
Moderate Renal Impairmentb
Placebo Empagliflozin
25 mg
Baseline Mean N 187 -- 187
Creatinine (mg/dL) 1.49 -- 1.46
eGFR (mL/min/1.73 m2) 44.3 -- 45.4
Week 12 Change N 176 -- 179
Creatinine (mg/dL) 0.01 -- 0.12
eGFR (mL/min/1.73 m2) 0.1 -- -3.8
Week 24 Change N 170 -- 171
Creatinine (mg/dL) 0.01 -- 0.10
eGFR (mL/min/1.73 m2) 0.2 -- -3.2
Week 52 Change N 164 -- 162
Creatinine (mg/dL) 0.02 -- 0.11
eGFR (mL/min/1.73 m2) -0.3 -- -2.8
Post-treatment Changec N 98 -- 103
Creatinine (mg/dL) 0.03 -- |
