Kerendia Drug Information

Kerendia 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 (T2DM). cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adult patients with heart failure with left ventricular ejection fraction (LVEF) ≥ 40%.

Prior to Initiation of Kerendia

Measure serum potassium levels and eGFR before initiation. Do not initiate treatment if serum potassium is > 5.0 mEq/L.

Recommended Starting Dosage

The recommended starting dose of Kerendia is based on eGFR and is presented in Table 1. Table 1: Recommended Starting Dosage For patients who are unable to swallow whole tablets, Kerendia may be crushed and mixed with water or soft foods such as applesauce immediately prior to use and administered orally.

Monitoring and Dosage Adjustment

CKD associated with T2DM The target daily dose of Kerendia is 20 mg orally. Measure serum potassium 4 weeks after initiating treatment and adjust dose (see Table 2 ); if serum potassium levels are > 4.8 to 5.0 mEq/L, initiation of Kerendia treatment may be considered with additional serum potassium monitoring within the first 4 weeks based on clinical judgment and serum potassium levels. Measure serum potassium 4 weeks after a dose adjustment and periodically throughout treatment, and adjust the dose as needed (see Table 2 ).

Table 2: Dose Adjustment Based on Current Serum Potassium Concentration and Current Dose (CKD associated with T2DM) Heart Failure with LVEF ≥ 40% The target daily dose of Kerendia for heart failure (LVEF ≥ 40%) is dependent on renal function (eGFR) at initiation of Kerendia treatment (see Table 3 ). The target daily dose is 40 mg orally once daily if eGFR at initiation is ≥ 60 mL/min/1.73m 2. Measure serum potassium and eGFR 4 weeks after initiating treatment and adjust dose (see Table 3 ).

Missed Doses Direct a patient to take a missed dose as soon as possible after it is noticed, but only on the same day. If this is not possible, the patient should skip the dose and continue with the next dose as prescribed.

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. Overall, serious adverse events occurred in 32% of patients receiving Kerendia and in 34% of patients receiving placebo in the FIDELIO-DKD study; the findings were similar in the FIGARO-DKD study. Permanent discontinuations due to adverse events also 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 was hyperkalemia. Hospitalization due to hyperkalemia for the Kerendia group was 0.9% vs 0.2% in the placebo group across both studies. Hyperkalemia led to permanent discontinuation of treatment in 1.7% receiving Kerendia versus 0.6% of patients receiving placebo across both studies.

Table 4 shows adverse reactions that occurred more commonly on Kerendia than on placebo, and in at least 1% of patients treated with Kerendia. The overall safety profile of Kerendia in the FINEARTS-HF study was largely consistent with the adverse reactions reported in patients with CKD and T2DM (Table 4). However, adverse reactions related to worsening renal function were reported more frequently in the Kerendia group (18%) compared with placebo (12%) in FINEARTS-HF.

The majority of events were reported to be mild to moderate. These events led to dose modifications in 9% of patients receiving Kerendia versus 4% of patients receiving placebo. Hospitalization due to events related to worsening of renal function for the Kerendia group was 2.0% versus 1.3% in the placebo group.

Laboratory Test 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 2-3 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.

Postmarketing Experience

The following additional adverse reactions have been reported in postmarketing experience with finerenone. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure: Hypersensitivity: Angioedema, Rash and Urticaria

Effect of Other Drugs on Kerendia Strong CYP3A4 Inhibitors Kerendia is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases finerenone exposure, which may increase the risk of Kerendia adverse reactions. Concomitant use of Kerendia with strong CYP3A4 inhibitors is contraindicated.

Avoid concomitant intake of grapefruit or grapefruit juice. Moderate and Weak CYP3A4 Inhibitors Kerendia is a CYP3A4 substrate. 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 Kerendia is a CYP3A4 substrate. Concomitant use of Kerendia with a strong or moderate CYP3A4 inducer decreases finerenone exposure, which may reduce the efficacy of Kerendia. Avoid concomitant use of Kerendia with strong or moderate CYP3A4 inducers.

Effect of Kerendia on Other Drugs CYP2C8 Substrates Kerendia is a weak CYP2C8 inhibitor at 40 mg. Kerendia increases exposure of CYP2C8 substrates at 40 mg dose, which may increase the risk of adverse reactions related to these substrates. Monitor patients more frequently for adverse reactions caused by sensitive CYP2C8 substrates if Kerendia 40 mg is co-administered with such substrates since minimal concentration changes may lead to serious adverse reactions.

Drugs That Affect Serum Potassium

More frequent serum potassium monitoring is warranted in patients receiving concomitant therapy with drugs or supplements that increase serum potassium.

Pregnancy Risk Summary 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 (see Data ). The clinical significance of these findings is unclear.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively.

Data Animal Data In the embryo-fetal toxicity study in rats, finerenone resulted in reduced placental weights and signs of fetal toxicity, including reduced fetal weights and retarded ossification at the maternal toxic dose of 10 mg/kg/day corresponding to an AUC unbound of at least 7 times that in humans. At 30 mg/kg/day, the incidence of visceral and skeletal variations was increased (slight edema, shortened umbilical cord, slightly enlarged fontanelle) and one fetus showed complex malformations including a rare malformation (double aortic arch) at an AUC unbound of about 10 times that in humans at the 40 mg dose and about 25 times that in humans at the 20 mg dose. The doses free of any findings (low dose in rats, high dose in rabbits) provide safety margins of 4 to 5 times for the AUC unbound expected in humans.

When rats were exposed during pregnancy and lactation in the pre- and postnatal developmental toxicity study, increased pup mortality and other adverse effects (lower pup weight, delayed pinna unfolding) were observed at about 2 or 4 times the AUC unbound expected in humans at the dose of 40 mg and 20 mg, respectively. In addition, the offspring showed slightly increased locomotor activity, but no other neurobehavioral changes starting at about 2 or 4 times the AUC unbound expected in humans at the dose of 40 mg and 20 mg, respectively. The dose free of findings provides a safety margin of about 2 times for the AUC unbound expected in humans for the 20 mg dose and is in the therapeutic range for the 40 mg dose.

Pediatric Use The safety and efficacy of Kerendia have not been established in patients below 18 years of age.

Kerendia is contraindicated in patients: Who are hypersensitive to any component of this product. Who are receiving concomitant treatment with strong CYP3A4 inhibitors. With adrenal insufficiency.

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

In the event of suspected overdose, immediately interrupt Kerendia treatment. The most likely manifestation of overdose is hyperkalemia. If hyperkalemia develops, standard treatment should be initiated.

Finerenone is unlikely to be efficiently removed by hemodialysis given its fraction bound to plasma proteins of about 90%.