Kerendia

Indications and Usage ( 1 ) 7/2025 Dosage and Administration ( 2.3 ) 7/2025 Contraindications ( 4 ) 7/2025 Warnings and Precautions ( 5.2 ) 7/2025

1 INDICATIONS AND USAGE 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%. Kerendia is a non-steroidal mineralocorticoid receptor antagonist (nsMRA) 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). ( 1 ) cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adult patients with heart failure with left ventricular ejection fraction (LVEF) ≥ 40% ( 1 )

2 DOSAGE AND ADMINISTRATION The recommended starting dosage is 10 mg or 20 mg orally once daily based on eGFR and serum potassium thresholds. ( 2.1 ) Increase dosage after 4 weeks to the target dose of 20 mg once daily for CKD and T2DM based on eGFR and serum potassium thresholds. ( 2.3 ) Increase dosage after 4 weeks to the target dose of 20 mg or 40 mg once daily for HF with LVEF ≥ 40% based on eGFR and serum potassium thresholds. ( 2.3 ) Tablets may be taken with or without food ( 2.2 ) 2.1 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 [see Warnings and Precautions (5.1) ]. 2.2 Recommended Starting Dosage The recommended starting dose of Kerendia is based on eGFR and is presented in Table 1. Table 1: Recommended Starting Dosage eGFR (mL/min/1.73m 2 ) Starting Dose ≥ 60 20 mg orally once daily ≥ 25 to 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 [see Warnings and Precautions (5.1) ]. Measure serum potassium 4 weeks after a dose adjustment and periodically throughout treatment, and adjust the dose as needed (see Table 2 ) [see Warnings and Precautions (5.1) and Drug Interactions (7.1) ]. Table 2: Dose Adjustment Based on Current Serum Potassium Concentration and Current Dose (CKD associated with T2DM) Current Kerendia Dose 10 mg once daily 20 mg once daily Current Serum Potassium (mEq/L) ≤ 4.8 Increase the dose to 20 mg once daily. If eGFR has decreased by more than 30% compared to previous measurement, maintain 10 mg dose. Maintain 20 mg once daily. > 4.8 – 5.5 Maintain 10 mg once daily. Maintain 20 mg once daily. > 5.5 Withhold Kerendia. Consider restarting at 10 mg once daily when serum potassium ≤ 5.0 mEq/L. Withhold Kerendia. Restart at 10 mg once daily when serum potassium ≤ 5.0 mEq/L. 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 . The target daily dose is 20 mg orally once daily if eGFR at initiation is ≥ 25 to < 60 mL/min/1.73m 2 . Measure serum potassium and eGFR 4 weeks after initiating treatment and adjust dose (see Table 3 ). Measure serum potassium and eGFR 4 weeks after a dose adjustment and monitor periodically throughout treatment, and adjust the dose as needed (see Table 3 ) [see Warnings and Precautions (5.1 & 5.2) and Drug Interactions (7.1) ]. Table 3: Dose Adjustment Based on Current Serum Potassium Concentration, eGFR, and Current Dose (Heart Failure (LVEF ≥ 40%)) Current Kerendia Dose 10 mg once daily 20 mg once daily 40 mg once daily Current Serum Potassium (mEq/L) < 5.0 Increase the dose to 20 mg once daily If eGFR has decreased by more than 30% compared to previous measurement, maintain current dose. Maintain 20 mg once daily if eGFR < 60 mL/min/1.73 m 2 at initiation. Otherwise increase the dose to 40 mg once daily Maintain 40 mg once daily. ≥ 5.0 to < 5.5 Maintain current dose. ≥ 5.5 to < 6.0 Withhold Kerendia. Restart at 10 mg once daily when serum potassium < 5.5 mEq/L. Decrease to 10 mg once daily. Decrease to 20 mg once daily. ≥ 6.0 Withhold Kerendia. Restart at 10 mg once daily when serum potassium < 5.5 mEq/L. If repeated serum potassium measurements are ≥5.5 mEq/L, restart Kerendia at 10 mg once daily when serum potassium < 5.0 mEq/L. 2.4 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.

3 DOSAGE FORMS AND STRENGTHS Kerendia is available as film-coated, oblong tablets in three strengths. 10 mg: pink, with "FI" on one side, "10" on the other side. 20 mg: yellow, with "FI" on one side, "20" on the other side. 40 mg: gray-orange, with "FI" on one side, "40" on the other side. Tablets: 10 mg, 20 mg, and 40 mg ( 3 )

4 CONTRAINDICATIONS Kerendia is contraindicated in patients: Who are hypersensitive to any component of this product [see Adverse Reactions (6.2) ] . Who are receiving concomitant treatment with strong CYP3A4 inhibitors [see Drug Interactions (7.1) ]. With adrenal insufficiency. Concomitant use with strong CYP3A4 inhibitors. ( 4 , 7.1 ) Patients with adrenal insufficiency. ( 4 ) Hypersensitivity to any component of this product. ( 4 )

6 ADVERSE REACTIONS The following serious adverse reactions are discussed elsewhere in the labeling: Hyperkalemia [see Warnings and Precautions (5.1) ] Adverse reactions occurring in ≥ 1% of patients on Kerendia and more frequently than placebo are hyperkalemia, hypotension, and hyponatremia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 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. CKD associated with T2DM The safety of Kerendia in patients with CKD associated with T2DM 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 and 2.9 years, respectively. 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 [see Warnings and Precautions (5.1) ]. 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. Table 4: Adverse reactions reported in ≥ 1% of patients on Kerendia and more frequently than placebo (Pooled data from FIDELIO-DKD and FIGARO-DKD) Adverse reactions Kerendia N = 6510 n (%) Placebo N = 6489 n (%) Hyperkalemia 912 (14.0) 448 (6.9) Hypotension 302 (4.6) 194 (3.0) Hyponatremia 82 (1.3) 47 (0.7) Heart Failure with LVEF ≥ 40% The safety of Kerendia in patients with heart failure (LVEF ≥40%) was evaluated in the randomized, double-blind, placebo-controlled, multicenter pivotal phase 3 study, FINEARTS-HF, in which a total of 2,993 patients were treated with 10 mg, 20 mg, or 40 mg once daily of Kerendia with a mean duration of treatment of 2.3 years. 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 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% 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. 6.2 Postmarketing Experience The following additional …

7 DRUG INTERACTIONS Strong CYP3A4 Inhibitors: Use is contraindicated. ( 7.1 ) Grapefruit or grapefruit juice: Avoid concomitant use. ( 7.1 ) Moderate or 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 ( 7.1 ) Strong or moderate CYP3A4 Inducers: Avoid concomitant use. ( 7.1 ) Sensitive CYP2C8 substrates at Kerendia 40 mg: Monitor more frequently for adverse reactions. ( 7.2 ) 7.1 Effect of Other Drugs on Kerendia Strong CYP3A4 Inhibitors Kerendia is a CYP3A4 substrate. Concomitant use with a strong CYP3A4 inhibitor increases finerenone exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of Kerendia adverse reactions. Concomitant use of Kerendia with strong CYP3A4 inhibitors is contraindicated [see Contraindications (4) ] . Avoid concomitant intake of grapefruit or grapefruit juice. Moderate and Weak CYP3A4 Inhibitors Kerendia is a CYP3A4 substrate. Concomitant use with a moderate or weak CYP3A4 inhibitor increases finerenone exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of Kerendia adverse reactions. 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 [see Dosing and Administration (2.3) and Drug Interaction (7.2) ] . Strong and Moderate CYP3A4 Inducers Kerendia is a CYP3A4 substrate. Concomitant use of Kerendia with a strong or moderate CYP3A4 inducer decreases finerenone exposure [see Clinical Pharmacology (12.3) ], which may reduce the efficacy of Kerendia. Avoid concomitant use of Kerendia with strong or moderate CYP3A4 inducers. 7.2 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 [see Clinical Pharmacology (12.3) ] , 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. 7.3 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. [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ].

8 USE IN SPECIFIC POPULATIONS Lactation: Breastfeeding not recommended ( 8.2 ) 8.1 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 2 to 4% and 15 to 20%, 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. 8.2 Lactation Risk Summary There are no data on the presence of finerenone or its metabolite in human milk, the effects on the breastfed infant or the effects of the drug on milk production. In a pre- and postnatal developmental toxicity study in rats, increased pup mortality and lower pup weight were observed at about 2 times the AUC unbound expected in humans. These findings suggest that finerenone is present in rat milk [see Use in Specific Populations (8.1) and Data ]. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the potential risk to breastfed infants from exposure to Kerendia, avoid breastfeeding during treatment and for 1 day after treatment. 8.4 Pediatric Use The safety and efficacy of Kerendia have not been established in patients below 18 years of age. 8.5 Geriatric Use Of the 6510 patients who received Kerendia in the FIDELIO-DKD and FIGARO-DKD studies, 55% of patients were 65 years and older, and 14% were 75 years and older. Of the 2993 patients who received Kerendia in the FINEARTS study, 79% of patients were 65 years and older, and 43% were 75 years and older. No overall differences in safety or efficacy were observed between these patients and younger patients. No dose adjustment is required. 8.6 Hepatic Impairment Avoid use of Kerendia in patients with severe hepatic impairment (Child Pugh C). No dosage adjustment is recommended in patients with mild or moderate hepatic impairment (Child Pugh A or B). Consider additional serum potassium monitoring in patients with moderate hepatic impairment (Child Pugh B) [see Dosing and …

12.1 Mechanism of Action Finerenone is a nonsteroidal, selective antagonist of the mineralocorticoid receptor (MR), which is activated by aldosterone and cortisol and regulates gene transcription. Finerenone blocks MR mediated sodium reabsorption and MR overactivation in both epithelial (e.g., kidney) and nonepithelial (e.g., heart, and blood vessels) tissues. MR overactivation is thought to contribute to fibrosis and inflammation. Finerenone has a high potency and selectivity for the MR and has no relevant affinity for androgen, progesterone, estrogen, and glucocorticoid receptors.

11 DESCRIPTION Kerendia contains finerenone, a nonsteroidal mineralocorticoid receptor antagonist. Finerenone's chemical name is ( 4S ) - 4-(4-cyano-2- methoxyphenyl)-5-ethoxy-2,8-dimethyl-1,4-dihydro-1,6-naphthyridine-3-carboxamide. The molecular formula is C 21 H 22 N 4 O 3 and the molecular weight is 378.43 g/mol. The structural formula is: Finerenone is a white to yellow crystalline powder. It is practically insoluble in water; and sparingly soluble in 0.1 M HCl, ethanol, and acetone. Each Kerendia tablet contains 10 mg, 20 mg, or 40 mg of finerenone. The inactive ingredients of Kerendia are lactose monohydrate, cellulose microcrystalline, croscarmellose sodium, hypromellose, magnesium stearate, and sodium lauryl sulfate. The film coating contains hypromellose, titanium dioxide and talc, in addition to ferric oxide red (10 mg and 40 mg strength tablets) or ferric oxide yellow (20 mg and 40 mg strength tablets). Chemical Structure

10 OVERDOSAGE 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%.

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Kerendia is available as a film-coated tablet in three strengths. The 10 mg is a pink oblong tablet with "FI" on one side of tablet and "10" on the other side of tablet. The 20 mg tablet is a yellow oblong tablet with "FI" on one side of tablet and "20" on the other side of tablet. The 40 mg tablet is a gray-orange oblong tablet with "FI" on one side of tablet and "40" on the other side of tablet. Kerendia Tablets 10 mg Bottle of 30 tablets NDC 50419-540-01 Bottle of 90 tablets NDC 50419-540-02 Hospital Blister Pack of 30 tablets NDC 50419-540-06 Kerendia Tablets 20 mg Bottle of 30 tablets NDC 50419-541-01 Bottle of 90 tablets NDC 50419-541-02 Hospital Blister Pack of 30 tablets NDC 50419-541-06 Kerendia Tablets 40 mg Bottle of 30 tablets NDC 50419-542-01 Bottle of 90 tablets NDC 50419-542-02 Hospital Blister Pack of 30 tablets NDC 50419-542-06 16.2 Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F ) [see USP Controlled Room Temperature].