2.4.3-Safety

FINEARTS-HF evaluated ~6000 adult patients with HF LVEF ≥40% taking KERENDIA or placebo

KERENDIA has a generally well-tolerated safety profile

Adverse reactions

Select sex-related AEs

Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo^1,3,4

Permanent discontinuations due to adverse events were similar between KERENDIA and placebo (3.2% vs 2.8%, respectively).

Adverse reactions related to worsening renal function were reported more frequently in the KERENDIA group (18%) vs placebo (12%) in FINEARTS-HF. The most frequently reported adverse reactions included renal impairment (7% vs 4%), eGFR decreased (5% vs 4%), acute kidney injury (4% vs 2%), and renal failure (3% vs 2%). The majority of events were reported to be mild to moderate. These events led to dose modifications in 9% receiving KERENDIA vs 4% receiving placebo. Hospitalization due to events related to worsening of renal function for the KERENDIA group was 2.0% vs 1.3% with placebo.

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 discontinuation. Initiation of KERENDIA may also cause a small increase in serum uric acid. This increase appears to attenuate over time.

eGFR=estimated glomerular filtration rate; HF=heart failure; HF LVEF=heart failure with left ventricular ejection fraction; LVEF=left ventricular ejection fraction.

Incidence of select sex-related adverse events was similar between KERENDIA and placebo¹⁰

Permanent discontinuations due to adverse events were similar between KERENDIA and placebo (3.2% vs 2.8%, respectively).

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.

*Includes breast and nipple tenderness. †Includes uterine, vaginal, and postmenopausal bleeding.

Trial Design Efficacy 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.

REFERENCES

KERENDIA has a generally well-tolerated safety profile

Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo1,3,4

Incidence of select sex-related adverse events was similar between KERENDIA and placebo10

Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo^1,3,4

Incidence of select sex-related adverse events was similar between KERENDIA and placebo¹⁰