b'B:8.75"T:8.25"S:7.25"NONCLINICAL TOXICOLOGY Liver InjuryCarcinogenesis, Mutagenesis, Impairment of Fertility Inform patients that ZEPOSIA (ozanimod) may increase liver enzymes. Advise patients that they should contact their Carcinogenesis healthcare provider if they have any unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine [see Warnings and Precautions].Oral administration of ozanimod (0, 8, 25, or 80 mg/kg/day) to Tg.rasH2 mice for 26-weeks resulted in an increase in hemangioma and hemangiosarcoma (combined) in males and females at the mid and high doses tested. Pregnancy and Fetal RiskOral administration of ozanimod (0, 0.2, 0.7, or 2 mg/kg/day) to rats for 2 years resulted in no increase in tumors.Inform patients that, based on animal studies, ZEPOSIA may cause fetal harm. Discuss with women of childbearing At the highest dose tested (2 mg/kg/day), plasma exposure (AUC) for ozanimod was approximately 100 timesage whether they are pregnant, might be pregnant, or are trying to become pregnant. Advise women of that in humans at the maximum recommended human dose (MRHD) of 0.92 mg/day. Plasma AUCs for majorchildbearing potential of the need for effective contraception during treatment with ZEPOSIA and for 3 months human metabolites, CC112273 and CC1084037, were similar to and less than, respectively, those in humansafter stopping ZEPOSIA. Advise a female patient to immediately inform her healthcare provider if she is pregnant or at the MRHD. planning to become pregnant [see Warnings and Precautions and Use in Specific Populations].Mutagenesis Respiratory EffectsOzanimod was negative in a battery of in vitro (Ames, mouse lymphoma tk) and in vivo (rat micronucleus) assays.Advise patients that they should contact their healthcare provider if they experience new onset or worsening Metabolite CC112273 was negative in in vitro (Ames, chromosomal aberration in mammalian cell) assays.dyspnea [see Warnings and Precautions].Metabolite CC1084037 was negative in an Ames assay, and positive in an in vitro chromosomal aberration assay in human (TK6) cells but negative in an in vivo rat micronucleus/comet assay. Macular EdemaImpairment of Fertility Advise patients that ZEPOSIA may cause macular edema, and that they should contact their healthcare provider if they experience any changes in their vision. Inform patient with diabetes mellitus or a history of uveitis that their Oral administration of ozanimod (0, 0.2, 2, or 30 mg/kg/day) to male and female rats prior to and during matingrisk of macular edema may be increased [see Warnings and Precautions].and continuing through gestation day 7 resulted in no adverse effects on fertility. At the highest dose tested (30 mg/kg/day), plasma ozanimod exposure (AUC) was approximately 1600 times that in humans at the maximumPosterior Reversible Encephalopathy Syndromerecommended human dose (MRHD) (0.92 mg/day); plasma AUCs for metabolites, CC112273 and CC1084037, atAdvise patients to immediately report to their healthcare provider any symptoms involving sudden onset of severe 30 mg/kg/day were 13 and 3 times, respectively, those in humans at the MRHD. headache, altered mental status, visual disturbances, or seizure. Inform patients that delayed treatment could lead PATIENT COUNSELING INFORMATION to permanent neurological consequences [see Warnings and Precautions].Advise the patient to read the FDA-approved patient labeling (Medication Guide). Immune System Effects after Stopping ZEPOSIARisk of Infections Advise patients that ZEPOSIA continues to have effects, such as lowering effects on peripheral lymphocyte count, for up to 3 months after the last dose [see Warnings and Precautions].Inform patients that they may be more likely to get infections, some of which could be life-threatening, when taking ZEPOSIA (ozanimod) and for 3 months after stopping it, and that they should contact their healthcare provider if they develop symptoms of infection [see Warnings and Precautions]. Inform patients that prior or concomitant use of drugs that suppress the immune system may increase the risk of infection. Advise patients thatManufactured for: Celgene Corporation some vaccines containing live virus (live attenuated vaccines) should be avoided during treatment with ZEPOSIA.Summit, NJ 07901Advise patients that if immunizations are planned, they should be administered at least 1 month prior to initiation of ZEPOSIA. Inform patients that the use of live attenuated vaccines should be avoided during and for 3 monthsZEPOSIA is a registered trademark of Celgene Corporation.after treatment with ZEPOSIA.2021 Celgene Corporation. All Rights Reserved.Cardiac Effects ZEPPI/ZEPMG.003Advise patients that initiation of ZEPOSIA treatment may result in a transient decrease in heart rate. Inform patientsMay 2021that to reduce this effect, dose titration is required. Advise patients that the dose titration is also required if a dose2084-US-210092405/21is missed for 1 day or more during the first 14 days of treatment [see Dosage and Administration and Warnings and Precautions].S:9.875" T:10.875" B:11.375"Cosmos Communications 1 Q1 Q2K ej44878b 07.14.21 133 1 Cosmos Communications 1 Q1 Q2K ej44878a 07.13.21 133 1PREPARED BY 11561844 US Branded Journal Ad A SIZE M25FRJob info Images FontsSpecial InstructionsDate: 7-1-2021 6:46 PM 2084_US_2100924_ZEPOSIA UC PBSNone 3 PG 4/C ad: spread followed by single page-Client: BMS 7x9.875_0521_wip2FNL.pdf (98%; 78KB) Create 5 pgs blank or greeked Brief Summary Product: OZANIMOD US pages for nowBuild mech to final A size specs Client Code: 2084-US-2101341 Additional InformationWF Issue # 8935889 NoneReleasing as: Native FilesFinal Size: NoneFinishing: NoneGutter: None Inks Additional Comments for SizingColors: 4/C & B/WBlack Single page 4/C specs: 8.25in x 10.875inLIVE: 7.25in*x 10in (.50 from trim edge)BLEED: 8.50in Team x 11.375inProducer: NoneAD: Phoebe FelizAE: Leah OKeeffe Scale: 1"= 1"QC: None Bleed 17" w x 11.375" h 17" w x 11.375" hProduction: Debi Post Trim/Flat 16.5" w x 10.875" h 16.5" w x 10.875" hDigital Artist: Eberhart, Thomas (NYC-FCB) Live/Safety 15.5" w x 9.875" h 15.5" w x 9.875" h FR Spellcheck:NonePath: PrePress:BMS:OZANIMOD:11561844:11561844_US_Branded_Ad_M25FR.indd_ _'