b'8USE IN SPECIFIC POPULATIONS 8.5Geriatric Use8.1Pregnancy Of the 2827 patients who received Kerendia in the FIDELIO-DKD Risk Summary study, 58% of patients were 65 years and older, and 15% were There are no available data on Kerendia use in pregnancy to75 years and older. No overall differences in safety or efficacy evaluateforadrug-associatedriskofmajorbirthdefects,were observed between these patients and younger patients. miscarriageoradversematernalorfetaloutcomes.AnimalNo dose adjustment is required.studies have shown developmental toxicity at exposures about8.6Hepatic Impairment4 times those expected in humans. (see Data). The clinicalAvoid use of Kerendia in patients with severe hepatic impairment significance of these findings is unclear.(Child Pugh C). TheestimatedbackgroundriskofmajorbirthdefectsandNo dosage adjustment is recommended in patients with mild or miscarriagefortheindicatedpopulationisunknown.Allmoderate hepatic impairment (Child Pugh A or B).pregnancieshaveabackgroundriskofbirthdefect,lossConsider additional serum potassium monitoring in patients or other adverse outcomes. In the U.S. general population,with moderate hepatic impairment (Child Pugh B) [see Dosing theestimatedbackgroundriskofmajorbirthdefectsandand Administration (2.3) and Clinical Pharmacology (12.3)].miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. 10OVERDOSAGEData Intheeventofsuspectedoverdose,immediatelyinterrupt Animal DataKerendia treatment. The most likely manifestation of overdose In the embryo-fetal toxicity study in rats, finerenone resulted inis hyperkalemia. If hyperkalemia develops, standard treatment reduced placental weights and signs of fetal toxicity, includingshould be initiated. reduced fetal weights and retarded ossification at the maternalFinerenone is unlikely to be efficiently removed by hemodialysis toxic dose of 10 mg/kg/day corresponding to an AUC unbound given its fraction bound to plasma proteins of about 90%. of 19 times that in humans. At 30 mg/kg/day, the incidence of visceral and skeletal variations was increased (slight edema,13NONCLINICAL TOXICOLOGYshortenedumbilicalcord,slightlyenlargedfontanelle)and13.1Carcinogenesis, Mutagenesis, Impairment of FertilityonefetusshowedcomplexmalformationsincludingarareFinerenone was non-genotoxic in an in vitro bacterial reverse malformation (double aortic arch) at an AUC unboundof aboutmutation (Ames) assay, the in vitro chromosomal aberration 25 times that in humans. The doses free of any findings (lowassay in cultured Chinese hamster V79 cells, or the in vivo dose in rats, high dose in rabbits) provide safety margins ofmicronucleus assay in mice.10 to 13 times for the AUC unboundexpected in humans.In2-yearcarcinogenicitystudies,finerenonedidnotshowa When rats were exposed during pregnancy and lactation instatistically significant increase in tumor response in Wistar rats the pre- and postnatal developmental toxicity study, increasedorinCD1mice.Inmalemice,Leydigcelladenomawas pup mortality and other adverse effects (lower pup weight,numericallyincreasedatadoserepresenting26timesthe delayed pinna unfolding) were observed at about 4 times theAUC unboundin humans and is not considered clinically relevant. AUC unbound expectedinhumans.Inaddition,theoff- Finerenone did not impair fertility in male rats but impaired fertility springshowedslightlyincreasedlocomotoractivity,in female rats at 20 times AUC to the maximum human exposure.butnootherneurobehavioralchangesstartingatabout17PATIENT COUNSELING INFORMATION4timestheAUC unbound expectedinhumans.ThedoseAdvise patients of the need for periodic monitoring of serum freeoffindingsprovidesasafetymarginofaboutpotassium levels. Advise patients receiving Kerendia to consult 2 times for the AUC unboundexpected in humans.with their physician before using potassium supplements or 8.2Lactation saltsubstitutescontainingpotassium[seeWarningsand Risk Summary Precautions (5.1)]. TherearenodataonthepresenceoffinerenoneoritsAdvise patients to avoid strong or moderate CYP3A4 inducers metabolite in human milk, the effects on the breastfed infantand to find alternative medicinal products with no or weak or the effects of the drug on milk production. In a pre- andpotential to induce CYP3A4 [see Drug Interactions (7.1)].postnataldevelopmentaltoxicitystudyinrats,increasedAvoid concomitant intake of grapefruit or grapefruit juice as it pup mortality and lower pup weight were observed at aboutis expected to increase the plasma concentration of finerenone 4 times the AUC unboundexpected in humans. These findings[see Drug Interactions (7.1)].suggestthatfinerenoneispresentinratmilk[seeUseinAdvise women that breastfeeding is not recommended at the Specific Populations (8.1) and Data]. When a drug is presenttime of treatment with KERENDIA and for 1 day after treatment in animal milk, it is likely that the drug will be present in human[see Use in Specific Populations (8.2)]. milk. Because of the potential risk to breastfed infants from 2021, Bayer HealthCare Pharmaceuticals Inc., All rights reserved.exposure to KERENDIA, avoid breastfeeding during treatment and for 1 day after treatment. Manufactured for:8.4Pediatric Use Bayer HealthCare Pharmaceuticals Inc.The safety and efficacy of Kerendia have not been establishedWhippany, NJ 07981 in patients below 18 years of age. Manufactured in Germany6711200BS3'