Adverse reactions : תופעות לוואי

8 ADVERSE REACTIONS
The following serious adverse reactions are discussed elsewhere in the labeling:
•     Hyperkalemia [see Warnings and Precautions (7.1)] 
8.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
The safety of Kerendia was evaluated in 2 randomized, double-blind, placebo-controlled, multicenter pivotal phase 3 studies FIDELIO-DKD and FIGARO-DKD, in which a total of 6510 patients were treated with 10 or 20 mg once daily over a mean duration of 2.2 years and 2.9 years, respectively.
Overall, serious adverse reactions occurred in 32% of patients receiving Kerendia and in 34% of patients receiving placebo in the FIDELIO-DKD study; the finding were similar in the FIGARO-DKD study. Permanent discontinuations due to adverse events occurred in a similar proportion of patients in the two studies (6-7% of patients receiving Kerendia and in 5-6% of patients receiving placebo).
The most frequently reported (≥ 10%) adverse reaction in both studies was hyperkalemia [see Warnings and Precautions (7.1)].
Table 3 shows adverse reactions that occurred more commonly on Kerendia than on placebo, and in at least 1% of patients treated with Kerendia.
Table 3: Adverse reactions reported in ≥ 1% of patients on Kerendia and more frequently than placebo (Pooled data from FIDELIO-DKD and FIGARO-DKD)

Kerendia                         Placebo
N=                               N=
Adverse reactions                        6510                             6489  n (%)                           n (%)

Hyperkalemia                                   912 (14.0)                      448 (6.9) 

Hypotension                                    302 (4.6)                       194 (3.9) 
47 (0.7)
Hyponatremia                                    82 (1.3)

Laboratory Test


Initiation of Kerendia may cause an initial small decrease in estimated GFR that occurs within the first 4 weeks of starting therapy, and then stabilizes. In a study that included patients with chronic kidney disease associated with type 2 diabetes, this decrease was reversible after treatment discontinuation.
Initiation of Kerendia may also cause a small increase in serum uric acid. This increase appears to attenuate over time.