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

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
• 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.

CV: bradycardia, heart block, hypertension, orthostatic hypotension.

EENT: macular edema.

GI: abdominal pain, ↑ liver enzymes.

Hemat: lymphopenia.

Neuro: pml, posterior reversible encephalopathy syndrome (pres).

Resp: ↓pulmonary function.
Misc: IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS), infection (including bacterial, viral and fungal), hypersensitivity reactions, MALIGNANCY.

Drug-Drug:

• 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.

Drug-Food:

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

• Capsules: 0.23 mg; 0.46 mg; 0.92 mg;

• 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.

Zeposia

• 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.

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

Therapeutic Classification: anti-multiple sclerosis agents

Pharmacologic Classification:

Absorption: Unknown.

Distribution: Extensively distributed to tissues.

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

Metabolism/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.

(plasma concentrations)

• 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 Appendix M); 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.
• 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 .

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