b'B:8.75"T:8.25"S:7.25"IMPORTANT SAFETY INFORMATION (cont\'d)Bradyarrhythmia and Atrioventricular Conduction Delays: Since initiation of ZEPOSIA may 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 drugswith ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertensionwith a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart blockLiverInjury:ElevationsofaminotransferasesmayoccurinpatientsreceivingZEPOSIA.Obtainliver functiontests,ifnotrecentlyavailable(i.e.,within6months),beforeinitiationofZEPOSIA.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 diseaseFetal Risk: There are no adequate and well-controlled studies in pregnant women. Based on animal studies,ZEPOSIAmaycausefetalharm.Womenofchildbearingpotentialshoulduseeffective contraception to avoid pregnancy during treatment and for 3 months after stopping ZEPOSIAIncreased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment andpersistedthroughouttreatment.Bloodpressureshouldbemonitoredduringtreatmentand managed appropriately. Certain foods that may contain very high amounts of 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 ZEPOSIARespiratory Effects: ZEPOSIA may cause a decline in pulmonary function. Spirometric evaluation of respiratory function should be performed during therapy, if clinically indicatedMacular 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, prior to treatment initiation and regular follow-up examinations. An ophthalmic evaluation is recommended in all patients at any time if there is a change in vision. Continued use of ZEPOSIA in patients with macular edema has notS:9.875" T:10.875" B:11.375"been evaluated; potential bene ts and risks for the individual patient should be considered if deciding whether ZEPOSIA should be discontinuedPosteriorReversibleEncephalopathySyndrome(PRES):RarecasesofPREShavebeenreported inpatientsreceivingaS1Preceptormodulator.IfaZEPOSIA-treatedpatientdevelopsunexpected 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 discontinuedUnintended Additive Immunosuppressive Effects From Prior Immunosuppressive or Immune-Modulating Drugs: When switching from drugs with prolonged immune effects, the half-life and mode of action of these drugs must be considered to avoid unintended additive immunosuppressive effects while at the same time minimizing risk of disease reactivation. Initiating treatment with ZEPOSIA after treatment with alemtuzumab is not recommendedImmune System Effects After Stopping ZEPOSIA: After discontinuing ZEPOSIA, the median 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 ZEPOSIAMostCommonAdverseReactions:Mostcommonadversereactions(incidence4%)are:livertest increased, upper respiratory infection, and headacheUse in Speci c Populations: Hepatic Impairment: Use is not recommendedFor 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. Data on File. OZA 025.Princeton, NJ: Bristol Myers Squibb.ZEPOSIA is a registered trademark of Celgene Corporation, a Bristol-Myers Squibb Company. 2021 Bristol-Myers Squibb Company. All rights reserved. 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