b"100 IMPORTANT SAFETY INFORMATION (cont'd)Progressive Multifocal Leukoencephalopathy (PML): (cont'd)PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.If con rmed, treatment with ZEPOSIA should be discontinued.BradyarrhythmiaandAtrioventricularConductionDelays:SinceinitiationofZEPOSIAmay result in a transient decrease in heart rate and atrioventricular conduction delays, dose titration is recommended to help reduce cardiac effects. Initiation of ZEPOSIA without dose escalation may result in greater decreases in heart rate. If treatment with ZEPOSIA is considered, advice from a cardiologist should be sought for those individuals: with signi cant QT prolongationwith arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugswithischemicheartdisease,heartfailure,historyofcardiacarrestormyocardialinfarction, cerebrovascular disease, and uncontrolled hypertensionwith a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart blockLiver Injury: Elevations of aminotransferases may occur in patients receiving ZEPOSIA. Obtain liver function tests, if not recently available (i.e., within 6 months), before initiation of ZEPOSIA. Patients who develop symptoms suggestive of hepatic dysfunction should have hepatic enzymes checked and ZEPOSIA should be discontinued if signi cant liver injury is con rmed. Caution should be exercised when using ZEPOSIA in patients with history of signi cant liver disease.Fetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies, ZEPOSIA may cause fetal harm. Women of childbearing potential should use effective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIA.Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatmentandpersistedthroughouttreatment.Bloodpressureshouldbemonitoredduring treatmentandmanagedappropriately.Certainfoodsthatmaycontainveryhighamountsof tyramine could cause severe hypertension in patients taking ZEPOSIA. Patients should be advised to avoid foods 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.Macular Edema: S1P modulators have been associated with an increased risk of macular edema. Patients with a history of uveitis or diabetes mellitus are at increased risk. Patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, priortotreatmentinitiationandregularfollow-upexaminations.Anophthalmicevaluationis recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has not been evaluated; potential bene ts and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinued.Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving a S1P receptor modulator. If a ZEPOSIA-treated patient develops unexpected neurological or psychiatric symptoms or any symptom/sign suggestive of an increase in intracranial pressure, a complete physical and neurological examination should be conducted. Symptoms of PRES are usually reversible but may evolve into ischemic stroke or cerebral hemorrhage. Delay in diagnosis and treatment may lead to permanent neurological sequelae. If PRES is suspected, treatment with ZEPOSIA should be discontinued.UnintendedAdditiveImmunosuppressiveEffectsFromPriorImmunosuppressiveor Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-lifeandmodeofactionofthesedrugsmustbeconsideredtoavoidunintendedadditive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommended.ImmuneSystemEffectsAfterStoppingZEPOSIA:AfterdiscontinuingZEPOSIA,themedian time for lymphocyte counts to return to the normal range was 30 days with approximately 90% of patients in the normal range within 3 months. Use of immunosuppressants within this period may lead to an additive effect on the immune system, therefore caution should be applied when initiating other drugs 4 weeks after the last dose of ZEPOSIA.Most Common Adverse Reactions ( 4): liver test increased, upper respiratory infection, and headache.Use in Speci c Populations: Hepatic Impairment: Use is not recommended.For additional safety information, please see Brief Summary of the Prescribing Information and the Medication Guide on the following pages.References: 1. ZEPOSIA. Prescribing information. Bristol-Myers Squibb Company; 2021. 2. Data on File. OZA 027. Princeton, NJ: Bristol Myers Squibb. 3. Sandborn WJ, Feagan BG, DHaens G, et al; True North Study Group. Ozanimod as induction and maintenance therapy for ulcerative colitis (supplementary appendix). N Engl J Med. 2021;385:1280-1291.ZEPOSIA and ZEPOSIA logo are trademarks of Celgene Corporation, a Bristol Myers Squibb company. 2022 Bristol-Myers Squibb Company. Printed in the USA. 2084-US-2200376 02/222084-US-2200376_ZEP_UC_Branded_JournalAd_Gastro_and_Hepa_P0157262_v01.indd 3 3/2/22 11:39 AM"