b'B:8.5"T:8.25"S:7.25"IMPORTANT SAFETY INFORMATION (CONTINUED) Macular Edema: S1P modulators have been associated Infections (Continued): with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Cases of fatal cryptococcal meningitis (CM) were reportedPatients with a history of these conditions should have in patients treated with another S1P receptor modulator.an ophthalmic evaluation of the fundus, including the If CM is suspected, ZEPOSIA should be suspended untilmacula, prior to treatment initiation and regular follow-up cryptococcal infection has been excluded. If CM is examinations. An ophthalmic evaluation is recommended diagnosed, appropriate treatment should be initiated. in all patients at any time if there is a change in vision.In clinical studies, patients who received ZEPOSIA wereContinued use of ZEPOSIA in patients with macular edema has not been evaluated; potential benefits and risks for not to receive concomitant treatment with antineoplastic,the individual patient should be considered if deciding non-corticosteroid immunosuppressive, or immune-whether ZEPOSIA should be discontinued.modulating therapies used for treatment of MS.Concomitant use of ZEPOSIA with any of these Posterior Reversible Encephalopathy Syndrome (PRES): therapies would be expected to increase the risk of Rare cases of PRES have been reported in patients immunosuppression. When switching to ZEPOSIA fromreceiving a S1P receptor modulator. If a ZEPOSIA-treated immunosuppressive medications, consider the duration ofpatient develops unexpected neurological or psychiatric their effects and their mode of action to avoid unintended symptoms or any symptom/sign suggestive of an additive immunosuppressive effects. increase in intracranial pressure, a complete physical andUse of live attenuated vaccines should be avoided neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic during and for 3 months after treatment with ZEPOSIA. Ifstroke or cerebral hemorrhage. Delay in diagnosis and live attenuated vaccine immunizations are required, treatment may lead to permanent neurological sequelae. administer at least 1 month prior to initiation of ZEPOSIA. If PRES is suspected, treatment with ZEPOSIA should be Progressive Multifocal Leukoencephalopathy (PML): PMLdiscontinued.is an opportunistic viral infection of the brain that typicallyUnintended Additive Immunosuppressive Effects From occurs in patients who are immunocompromised, and thatPrior Immunosuppressive or Immune-Modulating usually leads to death or severe disability. Drugs: When switching from drugs with prolonged PML has been reported in patients treated with S1Pimmune effects, the half-life and mode of action of these receptor modulators, including ZEPOSIA, and other MSdrugs must be considered to avoid unintended additive therapies and has been associated with some risk factors.immunosuppressive effects while at the same time If PML is suspected, withhold ZEPOSIA and perform anminimizing risk of disease reactivation. Initiating treatment appropriate diagnostic evaluation. with ZEPOSIA after treatment with alemtuzumab is not If confirmed, treatment with ZEPOSIA should berecommended.discontinued. Severe Increase in Multiple Sclerosis (MS) Disability After Bradyarrhythmia and Atrioventricular Conduction Delays:Stopping ZEPOSIA: In MS, severe exacerbation of disease, Since initiation of ZEPOSIA may result in a transientincluding disease rebound, has been rarely reported after decrease in heart rate and atrioventricular conductiondiscontinuation of a S1P receptor modulator. The possibility delays, dose titration is recommended to help reduceof severe exacerbation of disease should be considered cardiac effects. Initiation of ZEPOSIA without doseafter stopping ZEPOSIA treatment so patients should be escalation may result in greater decreases in heart rate.monitored upon discontinuation.If treatment with ZEPOSIA is considered, advice from aImmune System Effects After Stopping ZEPOSIA: After cardiologist should be sought for those individuals: discontinuing ZEPOSIA, the median time for lymphocyteS:9.875" T:10.5" B:11.375" with significant QT prolongation counts to return to the normal range was 30 days with with arrhythmias requiring treatment with Class 1a or IIIapproximately 90% of patients in the normal range withinanti-arrhythmic drugs 3 months. Use of immunosuppressants within this periodwith ischemic heart disease, heart failure, history ofmay lead to an additive effect on the immune system,cardiac arrest or myocardial infarction, cerebrovasculartherefore caution should be applied when initiating other disease, and uncontrolled hypertension drugs 4 weeks after the last dose of ZEPOSIA. with a history of Mobitz type II second-degree or higher Most Common Adverse Reactions ( 4%): upper AV block, sick sinus syndrome, or sino-atrial heart block respiratory infection, hepatic transaminase elevation, Liver Injury: Elevations of aminotransferases may occurorthostatic hypotension, urinary tract infection, back pain, in patients receiving ZEPOSIA. Obtain liver function tests,and hypertension.if not recently available (i.e., within 6 months), beforeUse in Specific Populations: Hepatic Impairment: Use is initiation of ZEPOSIA. Patients who develop symptomsnot recommended.suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinuedPlease see Important Safety Information throughout and if significant liver injury is confirmed. Caution should beBrief Summary of full Prescribing Information.exercised when using ZEPOSIA in patients with history of significant liver disease. References: 1. ZEPOSIA. Prescribing information. Bristol Myers Squibb; 2021.2. Comi G, Kappos L, Selmaj KW, et al; SUNBEAM Study Investigators. SafetyFetal Risk: There are no adequate and well-controlledand efficacy of ozanimod versus interferon beta-1a in relapsing multiplestudies in pregnant women. Based on animal studies,sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phaseZEPOSIA may cause fetal harm. Women of childbearing3 trial. Lancet Neurol. 2019;18(11):1009-1020. 3. Cohen JA, Comi G, Selmaj KW,potential should use effective contraception to avoidet al; RADIANCE Trial Investigators. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, pregnancy during treatment and for 3 months afterrandomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033.stopping ZEPOSIA. 4. Selmaj KW, Steinman L, Comi G, et al. Long-term safety and efficacy of Increased Blood Pressure: Increase in systolic pressureozanimod in relapsing multiple sclerosis: interim analysis of the DAYBREAK was observed after about 3 months of treatment andopen-label extension study. Presented at: 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS); 13-15 persisted throughout treatment. Blood pressure should beOctober 2021; The Digital Experience. 5. Selmaj KW, Steinman L, Comi G, et al.monitored during treatment and managed appropriately.Long-term safety and efficacy of ozanimod in relapsing multiple sclerosis Certain foods that may contain very high amounts ofin DAYBREAK: an open-label extension study of ozanimod phase 1-3 trials. tyramine could cause severe hypertension in patientsPresented at: 8th Joint ACTRIMS-ECTRIMS Meeting; September 11-13, 2020; taking ZEPOSIA. Patients should be advised to avoid foodsMSVirtual2020. Poster P0217.containing a very large amount of tyramine while taking ZEPOSIA.Respiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicated.ZEPOSIA and ZEPOSIA logo are trademarks of Celgene Corporation, a Bristol Myers Squibb company. All other trademarks are the property of their respective owners. 2022 Bristol-Myers Squibb Company. Printed in the USA. 2084-US-2200215 03/22PREPARED BY 11707081 BMS_MS_Spread Journal Ad - A-size M7FR11707081_BMS_MS_Spread Journal Ad_Asize_M7FR.indd 2 3/19/22 11:09 AMJob info Images FontsSpecial InstructionsDate: 3-19-2022 11:06 AM BMS Brand Image.ai (37.93%; 1.1MB),Montserrat (Regular, Bold, Medium, MediumNoneClient: BMS BMS_A077568_4C.tif (CMYK; 300 ppi; 100%;Italic), Arial Narrow (Regular)Product: ZEPOSIA 18.2MB), ZEPOSIA_US_TM_OD_CMYK_FC_Pos.Client Code: None ai (31.27%; 71KB) Additional InformationWF Issue # None NoneReleasing as: PDFx1AFinal Size:Finishing: NoneGutter: None Inks Additional Comments for SizingColors: NoneCyan, Magenta, Yellow, Black NoneTeam 4CProducer: Jessica SbailoAD: Joe MaranzinoAE: Carin Caselli Scale: 1"= 1"QC: None Bleed 16.25" w x 10.5" h 16.25" w x 10.5" hProduction: Steve Curry Trim/Flat 16.25" w x 10.5" h 16.25" w x 10.5" hDigital Artist: Kolosick, Tanya (NYC-SRX) Live/Safety 15.25" w x 9.875" h 15.25" w x 9.875" h Path: PrePress:BMS:OZANIMOD:11707081:_Packaged_Jobs:11707081_BMS_MS_Spread Journal Ad_Asize_M7FR:11707081_BMS_MS_Spread Journal Ad_Asize_M7FR.inddPDFX1A _'