Trade Name(s)

  • Zeposia

Ther. Class.

anti-multiple sclerosis agents

Pharm. Class.

receptor modulators


  • Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
  • Moderately to severely active ulcerative colitis.


Acts as a sphingosine 1-phosphate (S1P) receptor modulator that binds to SIP receptors 1 and 5, resulting in ↓ migration of lymphocytes from lymph nodes into peripheral blood, the CNS, and the intestine.

Therapeutic Effect(s):

  • ↓ frequency of relapses/delayed accumulation of disability in MS.
  • Achievement of clinical remission in ulcerative colitis.


Absorption: Unknown.

Distribution: Extensively distributed to tissues.

Protein Binding: Ozanimod: 98%;  CC112273: 99.8%;  CC1084037: 99%.

Metabolism and Excretion: Metabolized by several enzymes into 2 major active metabolites (CC112273 and CC1084037) and 3 minor active metabolites. These metabolites are further converted by multiple enzymes systems. Excreted in feces (37%) and urine (26%), primarily as inactive metabolites.

Half-life: Ozanimod: 21 hr;  CC112273 and CC1084037: 11 days.

TIME/ACTION PROFILE (plasma concentrations)

POunknown6–8 hr24 hr


Contraindicated in:

  • MI, unstable angina, stroke, TIA, decompensated HF requiring hospitalization, or class III or IV HF within previous 6 mo;
  • 2nd- or 3rd-degree heart block, sick sinus syndrome, or sinoatrial block (in the absence of a pacemaker);
  • Severe untreated sleep apnea;
  • Use of MAO inhibitor concurrently or within 14 days of last dose of ozanimod;
  • Active acute/chronic untreated infection;
  • Severe hepatic impairment;
  • OB:   Pregnancy.

Use Cautiously in:

  • QT interval prolongation (>450 msec in males, >470 msec females), hypokalemia, hypomagnesemia, congenital long QT syndrome, or concurrent use of QT interval prolonging medications;
  • Heart rate <55 bpm;
  • Cardiac arrhythmias requiring use of class Ia or III antiarrhythmics;
  • Ischemic heart disease, MI, HF, cardiac arrest, cerebrovascular disease, or uncontrolled hypertension;
  • Uveitis or diabetes mellitus (↑ risk of macular edema);
  • Immunocompromised or taking other immunosuppressant medications (↑ risk of progressive multifocal leukoencephalopathy [PML]);
  • Mild or moderate hepatic impairment (↓ dose);
  • Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
  • Rep:   Women of reproductive potential;
  • Pedi:   Safety and effectiveness not established in children;
  • Geri:  Risk of adverse reactions may be ↑ in older adults; consider age-related ↓ in cardiac/renal/hepatic function, chronic illnesses, and concurrent drug therapy.

Adverse Reactions/Side Effects

CV: bradycardia, heart block, hypertension, orthostatic hypotension

EENT: macular edema

GI: abdominal pain, ↑ liver enzymes

Hemat: lymphopenia


Resp: ↓ pulmonary function

Misc: IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS), INFECTION (including bacterial, viral and fungal), hypersensitivity reactions, MALIGNANCY

* CAPITALS indicate life-threatening.
Underline indicate most frequent.



  •  MAO inhibitors, including  phenelzine,  selegiline, and  linezolid, may ↑ risk of hypertensive crises; concurrent use or use within 14 days of last dose of ozanimod contraindicated.
  • ↑ risk of immunosuppression with  antineoplastics,  immunosuppressants, or  immune modulating therapies ; avoid initiating therapy with ozanimod after  alemtuzumab  therapy is discontinued.
  • Concurrent use of  QT-interval prolonging medications  may ↑ risk of QT interval prolongation and torsades de pointes; avoid concurrent use.
  •  Class Ia antiarrhythmics  and  class III antiarrhythmics may ↑ risk of torsades de pointes in presence of bradycardia; use concurrently with caution.
  •  Strong CYP2C8 inhibitors, including  gemfibrozil, may ↑ levels of active metabolite and risk of toxicity.
  •  Opioids,  SSRIs,  SNRIs,  TCAs  or  sympathomimetic drugs may ↑ risk of hypertensive crises.
  •  Live-attenuated vaccines  ↑ risk of infection; avoid concurrent use and for 3 mo following last dose.


Foods containing high amounts of tyramine (>150 mg) may lead to severe hypertension; avoid concurrent use.


PO (Adults): 0.23 mg once daily on Days 1–4, then 0.46 mg once daily on Days 5–7, then 0.92 mg once daily thereafter starting on Day 8.

Hepatic Impairment 
PO (Adults): Mild or moderate hepatic impairment: 0.23 mg once daily on Days 1–4, then 0.46 mg once daily on Days 5–7, then 0.92 mg every other day thereafter starting on Day 8.


Capsules: 0.23 mg, 0.46 mg, 0.92 mg


  • Assess ECG for pre-existing conduction abnormalities before starting therapy. May cause transient decrease in HR and atrioventricular conduction delays.
  • Monitor BP during therapy. May cause hypertension requiring treatment.
  • Perform ophthalmic exam to assess fundus, including the macula, before starting therapy in patients with a history of uveitis or macular edema.
  • Monitor for signs and symptoms of infection (fever, tiredness, body aches, chills, nausea, vomiting, headache, sore throat) before starting, periodically during and for 3 mo after therapy. Delay start of therapy until infection resolved. Interrupt therapy if serious infection occurs.
  • Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus, which may be fatal; hold dose and notify health care professional promptly. PML symptoms may begin gradually (hemiparesis, apathy, confusion, cognitive deficiencies, and ataxia) and may include deteriorating renal function. Performing an MRI may identify PML before clinical signs and symptoms occur. If PML confirmed, discontinue ozanimod.
  • Monitor for development of IRIS. Signs include clinical decline in patient's condition that may be rapid, can lead to serious neurological complications or death, and is often associated with characteristic changes on MRI. The time to onset of IRIS in patients with PML is generally within a few months after receptor modulator discontinuation.
  • Monitor for respiratory effects (reductions in forced expiratory volume and forced vital capacity) with spirometry periodically during therapy.
  • Monitor for signs and symptoms of posterior reversible encephalopathy syndrome (PRES) (impaired consciousness, convulsions, visual disturbances including blindness, loss of motor function, movement disorders, psychiatric disturbances, papilledema, visual impairment). Discontinue therapy if PRES develops. Usually reversible with discontinuation of ozanimod.
  • Assess for signs and symptoms of severe increased disability and disease exacerbation after stopping therapy with ozanimod.

Lab Test Considerations:

Obtain CBC with lymphocyte count before starting therapy. Peripheral blood lymphocytes return to normal range within 30 days to 3 mo.

  • Obtain AST, ALT, and bilirubin levels before starting therapy.
  • Test for antibodies to varicella zoster virus (VZV) in patients without a health care professional–confirmed history of varicella (chickenpox) or without documentation of a full course of vaccination against VZV before starting therapy.


  • Administer varicella zoster virus vaccination of antibody-negative patients before starting therapy. If live-attenuated vaccine immunizations are required, administer at least 1 mo before start of therapy. Avoid use of live-attenuated vaccines during and for 3 mo after therapy.
  • PO Administer once daily without regard to food.  DNC: Swallow capsules whole; do not crush, open, or chew. 
  • If a dose is missed during first 2 wk of therapy, restart using initial dosing regimen.

Patient/Family Teaching

  • Instruct patient to take ozanimod as directed. If a dose is missed during first 14 days of therapy, contact health care professional. Starting doses will need to be repeated. Do not discontinue therapy without consulting health care professional; may cause severe increase in disability. Advise patient to read  Medication Guide  before starting therapy and with each Rx refill in case of changes.
  • Advise patient to avoid foods or beverages containing tyramine (see food sources for specific nutrients); may cause a hypertensive crisis.
  • Instruct patient not to receive live-attenuated vaccines during and for 3 mo after treatment due to risk of infection. Patients who have not had a health care professional–confirmed history of chickenpox or documentation of a full course of vaccination should be tested for antibodies to VZV virus before starting therapy. Antibody-negative patients should receive vaccination prior to starting therapy, then postpone start of ozanimod for 1 mo to allow for full effect of vaccination.
  • Advise patient to notify health care professional immediately if signs and symptoms of infection (fever, cough, feeling very tired, painful and frequent urination, flu-like symptoms, rash, headache with fever, neck stiffness, sensitivity to light, nausea or confusion), PRES (sudden severe headache, sudden loss of vision or visual changes, sudden confusion, seizure), PML, or allergic reaction (rash, itchy hives, swelling of lips, tongue or face) occur.
  • Advise patient to notify health care professional if signs and symptoms of slow HR (dizziness, shortness of breath, light-headedness, confusion, feeling like heart is beating slowly or skipping beats, chest pain, tiredness), liver injury (unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, jaundice, dark urine), respiratory effects (new or worsening shortness of breath), or changes in vision (blurriness or shadows in the center of vision, a blind spot in center of vision, sensitivity to light, unusually colored vision) occur.
  • Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
  • Rep:  May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 3 mo after last dose. Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform pregnant patients of pregnancy exposure registry that monitors pregnancy outcomes in women exposed to ozanimod during pregnancy. To enroll patient in the pregnancy registry, call 1-877-301-9314 or visit www.zeposiapregnancyregistry.com.

Evaluation/Desired Outcomes

  • ↓ frequency of relapses/delayed accumulation of disability with MS.
  • Achievement of clinical remission in ulcerative colitis.