b'8USE IN SPECIFIC POPULATIONS 8.5Geriatric Use 85KERENDIA (finerenone) tablets, for oral use patientsreceivingplacebo.Hyperkalemialedtopermanent Initial U.S. Approval: 2021 discontinuationoftreatmentin2.3%ofpatientsreceiving8.1Pregnancy Of the 2827 patients who received Kerendia in the FIDELIO-DKD Kerendia versus 0.9% of patients receiving placebo. Risk Summary study, 58% of patients were 65 years and older, and 15% were BRIEF SUMMARY OF PRESCRIBING INFORMATION Themostfrequentlyreported(10%)adversereactionThere are no available data on Kerendia use in pregnancy to75 years and older. No overall differences in safety or efficacy CONSULT PACKAGE INSERT FOR washyperkalemia[seeWarningsandPrecautions(5.1)].evaluateforadrug-associatedriskofmajorbirthdefects,were observed between these patients and younger patients. FULL PRESCRIBING INFORMATION Hospitalization due to hyperkalemia for the Kerendia group wasmiscarriageoradversematernalorfetaloutcomes.AnimalNo dose adjustment is required.1.4% versus 0.3% in the placebo group.studies have shown developmental toxicity at exposures about8.6Hepatic Impairment1INDICATIONS AND USAGE 4 times those expected in humans. (see Data). The clinical Kerendia is indicated to reduce the risk of sustained eGFRTable 3 shows adverse reactions in FIDELIO-DKD that occurredsignificance of these findings is unclear.Avoid use of Kerendia in patients with severe hepatic impairment decline, end-stage kidney disease, cardiovascular death, non- more commonly on Kerendia than on placebo, and in at least(Child Pugh C). fatal myocardial infarction, and hospitalization for heart failure1% of patients treated with Kerendia. TheestimatedbackgroundriskofmajorbirthdefectsandNo dosage adjustment is recommended in patients with mild or in adult patients with chronic kidney disease (CKD) associatedmiscarriagefortheindicatedpopulationisunknown.Allmoderate hepatic impairment (Child Pugh A or B).Table 3: Adverse reactions reported in1% of patients onpregnancieshaveabackgroundriskofbirthdefect,loss with type 2 diabetes (T2D). Consider additional serum potassium monitoring in patients Kerendia and more frequently than placebo in theor other adverse outcomes. In the U.S. general population,with moderate hepatic impairment (Child Pugh B) [see Dosing 4CONTRAINDICATIONS phase 3 study FIDELIO-DKD theestimatedbackgroundriskofmajorbirthdefectsandand Administration (2.3) and Clinical Pharmacology (12.3)].Kerendia is contraindicated in patients:AdverseKerendia Placebo miscarriage in clinically recognized pregnancies is 2 to 4% andWhoarereceivingconcomitanttreatmentwithstrongreactions N = 2827 N = 2831 15 to 20%, respectively. 10OVERDOSAGE CYP3A4 inhibitors [see Drug Interactions (7.1)]. n (%) n (%) Data Intheeventofsuspectedoverdose,immediatelyinterruptWith adrenal insufficiency. Hyperkalemia 516 (18.3) 255 (9.0) Animal DataKerendia treatment. The most likely manifestation of overdose Hypotension 135 (4.8) 96 (3.4) In the embryo-fetal toxicity study in rats, finerenone resulted inis hyperkalemia. If hyperkalemia develops, standard treatment 5WARNINGS AND PRECAUTIONS Hyponatremia 40 (1.4) 19 (0.7) reduced placental weights and signs of fetal toxicity, includingshould be initiated. 5.1Hyperkalemia reduced fetal weights and retarded ossification at the maternalFinerenone is unlikely to be efficiently removed by hemodialysis Kerendia can cause hyperkalemia [(see Adverse Reactions (6.1)].Laboratory Test toxic dose of 10 mg/kg/day corresponding to an AUC unbound given its fraction bound to plasma proteins of about 90%. The risk for developing hyperkalemia increases with decreasingInitiation of Kerendia may cause an initial small decrease inof 19 times that in humans. At 30 mg/kg/day, the incidence of kidney function and is greater in patients with higher baselineestimated GFR that occurs within the first 4 weeks of startingvisceral and skeletal variations was increased (slight edema,13NONCLINICAL TOXICOLOGYpotassiumlevelsorotherriskfactorsforhyperkalemia.therapy, and then stabilizes. In a study that included patientsshortenedumbilicalcord,slightlyenlargedfontanelle)and13.1Carcinogenesis, Mutagenesis, Impairment of FertilityMeasureserumpotassiumandeGFRinallpatientsbeforewith chronic kidney disease associated with type 2 diabetes,onefetusshowedcomplexmalformationsincludingarareFinerenone was non-genotoxic in an in vitro bacterial reverse initiation of treatment with Kerendia and dose accordingly [seethis decrease was reversible after treatment discontinuation.malformation (double aortic arch) at an AUC unboundof aboutmutation (Ames) assay, the in vitro chromosomal aberration Dosage and Administration (2.1)]. Do not initiate Kerendia if25 times that in humans. The doses free of any findings (lowassay in cultured Chinese hamster V79 cells, or the in vivo serum potassium is 5.0 mEq/L.7DRUG INTERACTIONS dose in rats, high dose in rabbits) provide safety margins ofmicronucleus assay in mice.Measureserumpotassiumperiodicallyduringtreatment7.1CYP3A4 Inhibitors and Inducers 10 to 13 times for the AUC unboundexpected in humans.In2-yearcarcinogenicitystudies,finerenonedidnotshowa with Kerendia and adjust dose accordingly [see Dosage andStrong CYP3A4 Inhibitors When rats were exposed during pregnancy and lactation instatistically significant increase in tumor response in Wistar rats Administration(2.3)].MorefrequentmonitoringmaybeKerendia is a CYP3A4 substrate. Concomitant use with a strongthe pre- and postnatal developmental toxicity study, increasedorinCD1mice.Inmalemice,Leydigcelladenomawas necessaryforpatientsatriskforhyperkalemia,includingCYP3A4 inhibitor increases finerenone exposure [see Clinicalpup mortality and other adverse effects (lower pup weight,numericallyincreasedatadoserepresenting26timesthe thoseonconcomitantmedicationsthatimpairpotassiumPharmacology (12.3)], which may increase the risk of Kerendiadelayed pinna unfolding) were observed at about 4 times theAUC unboundin humans and is not considered clinically relevant. excretion or increase serum potassium [see Drug Interactionsadverse reactions. Concomitant use of Kerendia with strongAUC unbound expectedinhumans.Inaddition,theoff- Finerenone did not impair fertility in male rats but impaired fertility (7.1), 7.2)]. CYP3A4inhibitorsiscontraindicated[seeContraindicationsspringshowedslightlyincreasedlocomotoractivity,in female rats at 20 times AUC to the maximum human exposure.(4)]. Avoid concomitant intake of grapefruit or grapefruit juice.butnootherneurobehavioralchangesstartingatabout 6ADVERSE REACTIONS Moderate and Weak CYP3A4 Inhibitors 4timestheAUC unbound expectedinhumans.Thedose17PATIENT COUNSELING INFORMATIONThe following serious adverse reactions are discussed else- KerendiaisaCYP3A4substrate.ConcomitantusewithafreeoffindingsprovidesasafetymarginofaboutAdvise patients of the need for periodic monitoring of serum where in the labeling: moderateorweakCYP3A4inhibitorincreasesfinerenone2 times for the AUC unboundexpected in humans.potassium levels. Advise patients receiving Kerendia to consultHyperkalemia [see Warnings and Precautions (5.1)] exposure[seeClinicalPharmacology(12.3)],whichmaywith their physician before using potassium supplements or increasetheriskofKerendiaadversereactions.Monitor8.2Lactation saltsubstitutescontainingpotassium[seeWarningsand 6.1Clinical Trials Experience serum potassium during drug initiation or dosage adjustmentRisk Summary Precautions (5.1)]. Becauseclinicaltrialsareconductedunderwidelyvaryingof either Kerendia or the moderate or weak CYP3A4 inhibitor,TherearenodataonthepresenceoffinerenoneoritsAdvise patients to avoid strong or moderate CYP3A4 inducers conditions, adverse reaction rates observed in the clinical trialsand adjust Kerendia dosage as appropriate [see Dosing andmetabolite in human milk, the effects on the breastfed infantand to find alternative medicinal products with no or weak of a drug cannot be directly compared to rates in the clinicalAdministration (2.3) and Drug Interaction (7.2)]. or the effects of the drug on milk production. In a pre- andpotential to induce CYP3A4 [see Drug Interactions (7.1)].trials of another drug and may not reflect the rates observedpostnataldevelopmentaltoxicitystudyinrats,increasedAvoid concomitant intake of grapefruit or grapefruit juice as it in practice. Strong and Moderate CYP3A4 Inducers pup mortality and lower pup weight were observed at aboutis expected to increase the plasma concentration of finerenone ThesafetyofKerendiawasevaluatedintherandomized,Kerendia is a CYP3A4 substrate. Concomitant use of Kerendia4 times the AUC unboundexpected in humans. These findings[see Drug Interactions (7.1)].double-blind,placebo-controlled,multicenterpivotalphasewithastrongormoderateCYP3A4inducerdecreasessuggestthatfinerenoneispresentinratmilk[seeUseinAdvise women that breastfeeding is not recommended at the 3 study FIDELIO-DKD. In this study, 2827 patients receivedfinerenone exposure [see Clinical Pharmacology (12.3)], whichSpecific Populations (8.1) and Data]. When a drug is presenttime of treatment with KERENDIA and for 1 day after treatment Kerendia (10 or 20 mg once daily) and 2831 received placebo.may reduce the efficacy of Kerendia. Avoid concomitant use ofin animal milk, it is likely that the drug will be present in human[see Use in Specific Populations (8.2)]. ForpatientsintheKerendiagroup,themeandurationofKerendia with strong or moderate CYP3A4 inducers. milk. Because of the potential risk to breastfed infants from treatment was 2.2 years. 7.2Drugs That Affect Serum Potassium exposure to KERENDIA, avoid breastfeeding during treatment 2021, Bayer HealthCare Pharmaceuticals Inc., All rights reserved.Overall,seriousadversereactionsoccurredin32%ofMorefrequentserumpotassiummonitoringiswarrantedand for 1 day after treatment. Manufactured for:patients receiving Kerendia and in 34% of patients receivinginpatientsreceivingconcomitanttherapywithdrugsor8.4Pediatric Use Bayer HealthCare Pharmaceuticals Inc.placebo. Permanent discontinuation due to adverse reactionssupplements that increase serum potassium [see Dosage andThe safety and efficacy of Kerendia have not been establishedWhippany, NJ 07981 occurred in 7% of patients receiving Kerendia and in 6% ofAdministration (2.3) and Warnings and Precautions (5.1)]. in patients below 18 years of age. Manufactured in Germany6711200BS3'