formin + Sulfonylurea(N=156) INVOKANA 100 mg + Metformin+ Sulfonylurea(N=157) INVOKANA 300 mg + Metformin + Sulfonylurea(N=156)
Overall [N (%)] 24 (15.4) 43 (27.4) 47 (30.1)
Severe [N (%)]† 1 (0.6) 1 (0.6) 0
In Combination with Metformin + Sulfonylurea(52 weeks) Sitagliptin + Metformin + Sulfonylurea(N=378) INVOKANA 300 mg + Metformin + Sulfonylurea(N=377)
Overall [N (%)] 154 (40.7) 163 (43.2)
Severe [N (%)]† 13 (3.4) 15 (4.0)
In Combination with Metformin + Pioglitazone(26 weeks) Placebo + Metformin + Pioglitazone(N=115) INVOKANA 100 mg + Metformin + Pioglitazone(N=113) INVOKANA 300 mg + Metformin + Pioglitazone(N=114)
Overall [N (%)] 3 (2.6) 3 (2.7) 6 (5.3)
In Combination with Insulin(18 weeks) Placebo(N=565) INVOKANA 100 mg(N=566) INVOKANA 300 mg(N=587)
Overall [N (%)] 208 (36.8) 279 (49.3) 285 (48.6)
Severe [N (%)]† 14 (2.5) 10 (1.8) 16 (2.7)
Laboratory Tests
Increases in Serum Potassium
Dose-related, transient mean increases in serum potassium were observed early after initiation of INVOKANA (i.e., within 3 weeks) in a trial of patients with moderate renal impairment [see Clinical Studies (14.3)]. In this trial, increases in serum potassium of greater than 5.4 mEq/L and 15% above baseline occurred in 16.1%, 12.4%, and 27.0% of patients treated with placebo, INVOKANA 100 mg, and INVOKANA 300 mg, respectively. More severe elevations (i.e., equal or greater than 6.5 mEq/L) occurred in 1.1%, 2.2%, and 2.2% of patients treated with placebo, INVOKANA 100 mg, and INVOKANA 300 mg, respectively. In patients with moderate renal impairment, increases in potassium were more commonly seen in those with elevated potassium at baseline and in those using medications that reduce potassium excretion, such as potassium-sparing diuretics, angiotensin-converting-enzyme inhibitors, and angiotensin-receptor blockers [see Warnings and Precautions (5.2 and 5.3)].
Increases in Serum Magnesium
Dose-related increases in serum magnesium were observed early after initiation of INVOKANA (within 6 weeks) and remained elevated throughout treatment. In the pool of four placebo-controlled trials, the mean change in serum magnesium levels was 8.1% and 9.3% with INVOKANA 100 mg and INVOKANA 300 mg, respectively, compared to -0.6% with placebo. In a trial of patients with moderate renal impairment [see Clinical Studies (14.3)] , serum magnesium levels increased by 0.2%, 9.2%, and 14.8% with placebo, INVOKANA 100 mg, and INVOKANA 300 mg, respectively.
Increases in Serum Phosphate
Dose-related increases in serum phosphate levels were observed with INVOKANA. In the pool of four placebo controlled trials, the mean change in serum phosphate levels were 3.6% and 5.1% with INVOKANA 100 mg and INVOKANA 300 mg, respectively, compared to 1.5% with placebo. In a trial of patients with moderate renal impairment [see Clinical Studies (14.3)] , the mean serum phosphate levels increased by 1.2%, 5.0%, and 9.3% with placebo, INVOKANA 100 mg, and INVOKANA 300 mg, respectively.
Increases in Low-Density Lipoprotein Cholesterol (LDL-C) and non-High-Density Lipoprotein Cholesterol (non-HDL-C)
In the pool of four placebo-controlled trials, dose-related increases in LDL-C with INVOKANA were observed. Mean changes (percent changes) from baseline in LDL-C relative to placebo were 4.4 mg/dL (4.5%) and 8.2 mg/ |
