ZEPOSIA DOSING AND INITIATION

The Only Oral Advanced Therapya That Can Be Used Across All Moderate-to-Severe Lines of Therapy1-3

Recommended Dosage1

ZEPOSIA 7-day
Titration Schedule1
DAYS 1-4
0.23 mg
DAYS 5-7
0.46 mg
DAY 8
0.92 mg

The ZEPOSIA Starter Pack is designed to make the titration instructions easier to follow1

ZEPOSIA pill for ulcerative colitis starter pack

Initiate ZEPOSIA with a 7-day titration schedule, as shown in the graphic above. After initial titration, the recommended once-daily dosage of ZEPOSIA is 0.92 mg taken orally, starting on Day 8.1

  • An up-titration schedule should be used to reach the maintenance dose, as a transient decrease in heart rate and AV conduction delays may occur1
  • ZEPOSIA can be taken with or without food1

Additional Dosing Considerations

  • If a dose of ZEPOSIA is missed during the first 2 weeks of treatment, reinitiate treatment using the titration regimen1
  • If a dose of ZEPOSIA is missed after the first 2 weeks of treatment, continue with the treatment as planned1

aAdvanced therapies include S1P, biologics, and JAKi.

AV=atrioventricular; JAKi=Janus kinase inhibitor; S1P=sphingosine 1-phosphate.

Day 1 Observations

Heart Rate Observations During Clinical Trials (0.23 mg)1,4

Mean Heart Rate Over 6 Hours After First Dose (0.23 mg)4

ZEPOSIA for ulcerative colitis - mean heart rate changes chart

  • Since initiation of ZEPOSIA may result in a transient decrease in HR and AV conduction delays, an up-titration scheme is used to reach the maintenance dosage of ZEPOSIA1
  • With continued up-titration, the maximal heart rate effect of ozanimod occurred at Day 81
  • Initiation of ZEPOSIA may result in a transient decrease in heart rate. After the initial dose of ZEPOSIA 0.23 mg, the greatest mean decrease from baseline in heart rate occurred at Hour 5 on Day 1 (decrease 0.7 bpm in UC Study 1 and Study 3), returning to near baseline at Hour 61
  • In the induction studies,a bradycardia was reported on the day of treatment initiation in 1 patient (0.2%) treated with ZEPOSIA, compared to none in patients who received placebo1
    • After Day 1, bradycardia was reported in 1 patient (0.2%) treated with ZEPOSIA1
  • Bradycardia was not reported in the maintenance study1
  • ZEPOSIA was not studied in patients with a resting HR <55 bpm or those with preexisting cardiac conduction abnormalities1

AV Conduction Delays

No Mobitz type 2 second- or third-degree AV blocks were reported in UC Study 1 or UC Study 3 in patients treated with ZEPOSIA with dose titration.1

aUC Study 1 and UC Study 3.1

AV=atrioventricular; BPM=beats per minute; HR=heart rate; JAKi=Janus kinase inhibitor; S1P=sphingosine 1-phosphate; UC=ulcerative colitis.

Getting Patients Started on ZEPOSIA

Screening for All Patients Prior to First Dose—Within the Last 6 Months1

  • Obtain blood work
    • Complete blood count (CBC), including lymphocyte count (within the last 6 months or after discontinuation of prior UC therapy)
    • Transaminase and total bilirubin levels
  • Obtain a one-time electrocardiogram (ECG) to determine whether pre-existing conduction abnormalities are presenta

ZEPOSIA is contraindicated in patients who have the presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker.1

Screening Only for Select Patients Prior to First Dose1

  • With a history of uveitis, macular edema, or diabetes mellitus—ophthalmic evaluation of the fundus, including the maculab
  • Without documentation of history of VZV/chicken pox, or documentation of a full course of vaccination, test for antibodiesc
    • If live attenuated immunizations are required, administer at least 1 month prior to initiation

Evaluate current and prior medications before initiation of treatment1

At home appointment icon

Support provided by Bristol Myers Squibb at the Homes of Eligible Patientsd

  • Blood work
  • ECG with cardiologist overread
  • Macular edema screening with licensed eye clinician overread
  • VZV antibody testing

The full Prescribing Information for ZEPOSIA does not require routine lab monitoring unless clinically indicated

aIn patients with certain preexisting conditions, advice from a cardiologist should be sought—see Warnings and Precautions in Prescribing Information. ZEPOSIA was not studied in patients who had: Cardiac conduction or rhythm disorders, including sick sinus syndrome, significant QT prolongation (QTcF >450 msec in males, >470 msec in females), risk factors for QT prolongation, or other conduction abnormalities or cardiac condition that in the opinion of the treating investigator could jeopardize the patient's health.1
bPatients with a history of uveitis and patients with a history of diabetes mellitus are at increased risk of macular edema during ZEPOSIA therapy. The incidence of macular edema is also increased in patients with a history of uveitis. In addition to the examination of the fundus, including the macula, prior to treatment, patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations.1
cVZV vaccination of antibody-negative patients is recommended prior to commencing treatment.1
dHome visits for initial routine medical tests are not available to people enrolled in Medicare, Medicaid, or other federal or state healthcare programs, or to people living in Rhode Island.

QTcF=corrected QT interval by Fridericia; UC=ulcerative colitis; VZV=varicella-zoster virus.

ZEPOSIA Dosing, Initiation, and Patient Brochure

Read more about getting your patients started on ZEPOSIA

Download the Dosing, Initiation, and Patient Support Guide

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Find helpful resources to help your patients start and stay on therapy with ZEPOSIA

RESOURCES

References: 1. ZEPOSIA. Prescribing Information. Celgene Corporation, a Bristol Myers Squibb company. 2. Rinvoq [package insert]. North Chicago, Illinois: AbbVie Biotechnology Ltd; 2022. 3. Xeljanz [package insert]. New York, New York: Pfizer Inc; 2021. 4. Data on file. BMS-REF-OZA-023. Princeton, NJ: Bristol-Myers Squibb Company; 2021.

IMPORTANT SAFETY INFORMATION

INDICATIONS

ZEPOSIA® (ozanimod) is indicated for the treatment of:

  1. Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.
  2. Moderately to severely active ulcerative colitis (UC) in adults.

IMPORTANT SAFETY INFORMATION

Contraindications:

  • Patients who in the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III/IV heart failure or have a presence of Mobitz type II second-degree or third-degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker
  • Patients with severe untreated sleep apnea
  • Patients taking a monoamine oxidase (MAO) inhibitor

Infections: ZEPOSIA may increase the susceptibility to infections. Life-threatening and rare fatal infections have occurred in patients receiving ZEPOSIA. Obtain a recent (i.e., within 6 months or after discontinuation of prior MS or UC therapy) complete blood count (CBC) including lymphocyte count before initiation of ZEPOSIA. Delay initiation of ZEPOSIA in patients with an active infection until the infection is resolved. Consider interruption of treatment with ZEPOSIA if a patient develops a serious infection. Continue monitoring for infections up to 3 months after discontinuing ZEPOSIA.

  • Herpes zoster was reported as an adverse reaction in ZEPOSIA-treated patients. Herpes simplex encephalitis and varicella zoster meningitis have been reported with sphingosine 1-phosphate (S1P) receptor modulators. Patients without a healthcare professional-confirmed history of varicella (chickenpox), or without documentation of a full course of vaccination against varicella zoster virus (VZV), should be tested for antibodies to VZV before initiating ZEPOSIA. A full course of vaccination for antibody-negative patients with varicella vaccine is recommended prior to commencing treatment with ZEPOSIA.
  • Cases of fatal cryptococcal meningitis (CM) were reported in patients treated with another S1P receptor modulator. If CM is suspected, ZEPOSIA should be suspended until cryptococcal infection has been excluded. If CM is diagnosed, appropriate treatment should be initiated.
  • In the MS and UC clinical studies, patients who received ZEPOSIA were not to receive concomitant treatment with antineoplastic, non-corticosteroid immunosuppressive, or immune-modulating therapies used for treatment of MS and UC. Concomitant use of ZEPOSIA with any of these therapies would be expected to increase the risk of immunosuppression. When switching to ZEPOSIA from immunosuppressive medications, consider the duration of their effects and their mode of action to avoid unintended additive immunosuppressive effects.
  • Use of live attenuated vaccines should be avoided during and for 3 months after treatment with ZEPOSIA. If live attenuated vaccine immunizations are required, administer at least 1 month prior to initiation of ZEPOSIA.

Progressive Multifocal Leukoencephalopathy (PML): PML is an opportunistic viral infection of the brain that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability.

PML has been reported in patients treated with S1P receptor modulators, including ZEPOSIA, and other MS and UC therapies and has been associated with some risk factors. If PML is suspected, withhold ZEPOSIA and perform an appropriate diagnostic evaluation.

If confirmed, treatment with ZEPOSIA should be discontinued.

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 significant QT prolongation
  • with arrhythmias requiring treatment with Class 1a or III anti-arrhythmic drugs
  • with ischemic heart disease, heart failure, history of cardiac arrest or myocardial infarction, cerebrovascular disease, and uncontrolled hypertension
  • with a history of Mobitz type II second-degree or higher AV block, sick sinus syndrome, or sino-atrial heart block

Liver 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 significant liver injury is confirmed. Caution should be exercised when using ZEPOSIA in patients with history of significant 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. Women who become pregnant while taking ZEPOSIA for MS may enroll in the ZEPOSIA pregnancy registry by calling 1-877-301-9314 or visiting www.zeposiapregnancyregistry.com.

Increased Blood Pressure: Increase in systolic pressure was observed after about 3 months of treatment and persisted throughout treatment. Blood pressure should be monitored during treatment and 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 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, 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 not been evaluated; potential benefits 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.

Unintended 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 recommended.

Severe Increase in Multiple Sclerosis (MS) Disability After Stopping ZEPOSIA: In MS, severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator. The possibility of severe exacerbation of disease should be considered after stopping ZEPOSIA treatment so patients should be monitored upon discontinuation.

Immune 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 ZEPOSIA.

Most Common Adverse Reactions that occurred in the MS clinical trials of ZEPOSIA-treated patients (≥ 4%): upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.

In the UC clinical trials, the most common adverse reactions that occurred in ≥4% of ZEPOSIA-treated patients and greater than in patients who received placebo were upper respiratory infection, liver test increased, and headache.

Use in Specific Populations: Hepatic Impairment: Use is not recommended.

For additional safety information, please see the full Prescribing Information and Medication Guide

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Indications:

Moderately to severely active ulcerative colitis (UC) in adults
ULCERATIVE COLITIS
Relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults
MULTIPLE SCLEROSIS