1.4.5-Safety

KERENDIA was generally well-tolerated in trials that included >13,000 adult patients with CKD associated with T2D

Adverse reactions

Select sex-related AEs

Adverse reactions reported in ≥1% of patients taking KERENDIA and more frequently than placebo (pooled data from FIGARO-DKD and FIDELIO-DKD)^1,27

Blood pressure safety

AE=adverse event; CKD=chronic kidney disease; T2D=type 2 diabetes.

Incidence of reproductive system and breast disorders was similar between KERENDIA and placebo

Use in pregnancy: There are no available data on KERENDIA use in pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal studies have shown developmental toxicity at exposures about 2 times those expected in humans. The clinical significance of these findings is unclear.¹

Initiation of KERENDIA may cause an initial small increase in blood creatinine levels (mean change <0.1 mg/dL) and a small decrease in eGFR (mean change 2 to 3 mL/min) that occurs within the first 4 weeks of starting therapy and then stabilizes. These changes were reversible after treatment discontinuation¹
Initiation of KERENDIA may also cause a small increase in serum uric acid. This increase appears to attenuate over time¹

AE=adverse event; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; T2D=type 2 diabetes.

Trial Design CV Data Renal Data UACR Safety

IMPORTANT SAFETY INFORMATION AND INDICATIONS

CONTRAINDICATIONS:

Hypersensitivity to any component of this product
Concomitant use with strong CYP3A4 inhibitors
Patients with adrenal insufficiency

WARNINGS AND PRECAUTIONS:

Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia

Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5 mEq/L. Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium.
Worsening of Renal Function in Patients with Heart Failure: KERENDIA can cause worsening of renal function in patients with heart failure. Rarely, severe events associated with worsening renal function, including events requiring hospitalization, have been observed

Measure eGFR in all patients before initiation of treatment or with dose titration of KERENDIA and dose accordingly. Initiation of KERENDIA in patients with heart failure and an eGFR <25 mL/min/1.73 m² is not recommended. Measure eGFR periodically during maintenance treatment with KERENDIA in patients with heart failure. Consider delaying up-titration or interrupting treatment with KERENDIA in patients who develop clinically significant worsening of renal function

MOST COMMON ADVERSE REACTIONS:

CKD associated with T2D: From the pooled data of FIDELIO-DKD and FIGARO-DKD, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (14% vs 6.9%), hypotension (4.6% vs 3%), and hyponatremia (1.3% vs 0.7%).
HF LVEF ≥40%: From FINEARTS-HF, the adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo were hyperkalemia (9.7% vs 4.2%), hypotension (7.6% vs 4.7%), and hyponatremia (1.9% vs 0.9%). Events related to worsening renal function were reported more frequently in the KERENDIA group (18%) compared with placebo (12%).

DRUG INTERACTIONS:

Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice.
Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor, and adjust KERENDIA dosage as appropriate.
Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers.
Sensitive CYP2C8 Substrates at KERENDIA 40mg: Monitor patients more frequently for adverse reactions caused by sensitive CYP2C8 substrates if KERENDIA 40mg is co-administered with such substrates, since minimal concentration changes may lead to serious adverse reactions.

USE IN SPECIFIC POPULATIONS:

Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment.
Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B).

INDICATIONS:

KERENDIA (finerenone) is indicated to reduce the risk of:

sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, cardiovascular death, non-fatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D) (10mg, 20mg tablets)
cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adult patients with heart failure with left ventricular ejection fraction (HF LVEF) ≥40% (10mg, 20mg, 40mg tablets)

Please see the full Prescribing Information for KERENDIA.

*Mixed-model exploratory analysis with covariate factors of treatment group, eGFR category, albuminuria type, treatment time and baseline value, and baseline value time.

CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; LS=least-squares; SBP=systolic blood pressure; T2D=type 2 diabetes.

REFERENCES

KERENDIA was generally well-tolerated in trials that included >13,000 adult patients with CKD associated with T2D

Adverse reactions reported in ≥1% of patients taking KERENDIA and more frequently than placebo (pooled data from FIGARO-DKD and FIDELIO-DKD)1,27

Incidence of reproductive system and breast disorders was similar between KERENDIA and placebo

SBP changes from baseline at month 1

Across all quartiles, patients were on an average of 3+ antihypertensive therapies at baseline

Adverse reactions reported in ≥1% of patients taking KERENDIA and more frequently than placebo (pooled data from FIGARO-DKD and FIDELIO-DKD)^1,27