ozanimod (Rx)

Brand and Other Names:Zeposia
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Dosing & Uses


Dosage Forms & Strengths


  • 0.23mg

  • 0.46mg

  • 0.92mg

Multiple Sclerosis

Indicated for relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease

Initial dose titration and maintenance

  • Days 1-4: 0.23 mg PO qDay
  • Days 5-7: 0.46 mg PO qDay
  • Day 8 and thereafter: 0.92 mg PO qDay

Ulcerative Colitis

Indicated for moderate-to-severe active ulcerative colitis

Initial dose titration and maintenance

  • Days 1-4: 0.23 mg PO qDay
  • Days 5-7: 0.46 mg PO qDay
  • Day 8 and thereafter: 0.92 mg PO qDay

Dosage Modifications

Reinitiation after treatment interruption

  • First 2 weeks of treatment: Reinitiate treatment using the titration regimen if a dose is missed
  • After first 2 weeks of treatment: Continue with treatment as planned if a dose is missed

Renal impairment

  • All severities: No dosage adjustment required

Hepatic impairment

  • Not recommended; effect of hepatic impairment on the pharmacokinetics of the ozanimod major active metabolites is unknown

Dosing Considerations

Laboratory and examinations before initiating

  • CBC count: Obtain recent (ie, within last 6 months or after discontinuing prior MS therapy) count, including lymphocyte count
  • ECG: Determine if preexisting conduction abnormalities are present; consult cardiologist for patients with known preexisting conditions
  • Liver function tests: Obtain recent (ie, within last 6 months) transaminase and bilirubin levels
  • Ophthalmic assessment: In patients with history of uveitis or macular edema, evaluate fundus, including the macula

Assess medications

  • Current or prior medications
    • Assess for additive immunosuppressive effects of current or past medications (eg, antineoplastics, immunosuppressives, immunomodulators)
    • Assess for drugs that could slow heart rate or atrioventricular conduction
  • Vaccinations
    • Test for antibodies to varicella-zoster virus (VZV) before initiating
    • VZV vaccination of antibody-negative patients recommended before initiating ozanimod
    • If live attenuated vaccine immunizations required, administer at least 1 month before initiating ozanimod

Safety and efficacy not established



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            Adverse Effects


            Upper respiratory tract infection (26%)


            Elevated hepatic transaminases (10%)

            Orthostatic hypotension (4%)

            Urinary tract infection (4%)

            Back pain (4%)

            Hypertension (4%)

            Upper abdominal pain (2%)


            Macular edema


            Frequency Not Defined

            Hypersensitivity, including rash and urticaria

            Dose-dependent FEV1 and FVC reduction




            MI, unstable angina, stroke, TIA, decompensated heart failure (HF) requiring hospitalization, or Class III or IV HF within the last 6 months

            Mobitz type II second- or third-degree atrioventricular (AV) block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker

            Severe untreated sleep apnea



            Based on animal studies, may cause fetal harm

            Clinical trials reported increased systolic blood pressure; monitor blood pressure during treatment and manage appropriately

            Dose-dependent reductions in FEV1 and FVC reported; perform spirometric evaluation of respiratory function during therapy, if clinically indicated

            Rare cases of posterior reversible encephalopathy syndrome reported in patients receiving a S1P receptor modulator

            Liver injury

            • Use in patients with hepatic impairment not recommended; obtain transaminase and bilirubin levels, if not recently available (ie, within 6 months), before initiation of therapy
            • Check hepatic enzymes in patients who develop symptoms suggestive of hepatic dysfunction, such as unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine; discontinue therapy if significant liver injury confirmed

            Progressive multifocal leukoencephalopathy (PML)

            • PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically occurs in patients who are immunocompromised, and that usually leads to death or severe disability
            • Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes
            • PML has been reported in patients treated with S1P receptor modulators and other multiple sclerosis (MS) and UC therapies and has been associated with some risk factors (eg, immunocompromised patients, polytherapy with immunosuppressants)
            • Physicians should be vigilant for clinical symptoms or MRI findings that may be suggestive of PML; MRI findings may be apparent before clinical signs or symptoms
            • If PML is suspected, treatment should be suspended until PML has been excluded by an appropriate diagnostic evaluation; if PML is confirmed, treatment should be discontinued
            • In MS, severe exacerbation of disease, including disease rebound, rarely reported after discontinuation of a S1P receptor modulator; possibility of severe exacerbation of disease should be considered after stopping treatment
            • Patients should be observed for a severe increase in disability upon therapy discontinuation; appropriate treatment should be instituted, as required

            Macular edema

            • An ophthalmic evaluation of the fundus, including macula, recommended in all patients at any time if there is any change in vision while taking medication
            • Continuation of therapy in patients with macular edema not evaluated; a decision on whether or not therapy should be discontinued needs to take into account potential benefits and risks for individual patient
            • Patients with a history of uveitis and patients with a history of diabetes mellitus are at increased risk of macular edema during therapy; the incidence of macular edema is also increased in patients with a history of uveitis
            • In addition to examination of the fundus, including macula, prior to treatment, patients with diabetes mellitus or a history of uveitis should have regular follow-up examinations


            • May cause a mean reduction in peripheral blood lymphocyte count to 45% of baseline values because of reversible sequestration of lymphocytes in lymphoid tissue
            • Increased risk of susceptibility to infections (eg, viral upper respiratory tract infections, urinary tract infections, herpes infections)
            • Life-threatening and rare fatal infections have occurred
            • Delay initiation in patients with an active infection until it is resolved
            • Consider interrupting treatment if serious infection develops
            • Owing to drug’s long half-life, continue monitoring for infections for 3 months

            Bradyarrhythmias and AV conduction delays

            • Dose initiation may result in transient decrease in HR and AV conduction delays; follow titration schedule to reach maintenance dose
            • Obtain cardiology consultation for patients with
              • Significant QT prolongation (QTcF >450 msec in males, >470 msec in females)
              • Arrhythmias requiring treatment with Class 1a or Class III antiarrhythmic drugs
              • Ischemic heart disease, HF, history of cardiac arrest or MI, CV disease, and uncontrolled hypertension
              • History of second-degree Mobitz type II or higher AV block, sick sinus syndrome, or sinoatrial heart block

            Drug interaction overview

            • Immunosuppressants, immunomodulators, or antineoplastics
              • After discontinuing ozanimod, the median time for peripheral blood lymphocytes to return to the normal range was 30 days, with ~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, and, therefore, caution should be applied when initiating other drugs 4 weeks after the last ozanimod dose
              • Conversely, 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, when initiating ozanimod
              • Initiating ozanimod after treatment with alemtuzumab is not recommended
            • Antiarrhythmic drugs, QT-prolonging drugs, or drugs that decrease HR
              • Has not been studied in patients taking QT-prolonging drugs
              • Obtain cardiology consultation to assess risk
              • Class Ia (eg, quinidine, procainamide) and Class III (eg, amiodarone, sotalol) antiarrhythmic drugs have been associated with cases of torsades de pointes in patients with bradycardia
              • Because of the potential additive effects on heart rate, treatment with ozanimod should generally not be initiated in patients who are concurrently treated with QT-prolonging drugs
            • Vaccination
              • Vaccinations may be less effective during and up to 3 months after discontinuing ozanimod
              • Owing to risk of infection, avoid live attenuated vaccines during treatment and for up to 3 months after discontinuation
            • CYP2C8 inhibitor and inducers
              • Active metabolites are metabolized by CYP2C8
              • Strong CYP2C8 inhibitors: Coadministration is not recommended owing to increased systemic exposure of active metabolites and risk of adverse effects
              • Strong CYP2C8 inducers: Avoid coadministration; may decrease systemic exposure and efficacy
            • BCRP inhibitors
              • Coadministration is not recommended owing to increased systemic exposure of active metabolites and risk of adverse effects
            • MAOIs
              • Coadministration with MAO-B inhibitors may decrease exposure of the active metabolites of ozanimod
              • Additionally, metabolites of ozanimod may inhibit MAO
              • The potential for a clinical interaction with MAOIs has not been studied; however, the increased risk of nonselective MAOI may lead to hypertensive crisis
              • Therefore, coadministration with MAOI (eg, selegiline, phenelzine, linezolid) is contraindicated
              • At least 14 days should elapse between discontinuation and initiation of treatment with MAO inhibitors
            • Adrenergic and serotonergic drugs
              • Because an active metabolite of ozanimod inhibits MAO-B in vitro, there is a potential for serious adverse reactions, including hypertensive crisis
              • Coadministration with drugs or OTC medications that can increase norepinephrine or serotonin (eg, opioid drugs, SSRIs, SNRIs, tricyclics, tyramine) is not recommended
              • Monitor patients for hypertension with concomitant sympathomimetic use
            • Tyramine
              • MAO in the GI tract and liver (primarily type A) provides protection from exogenous amines (eg. tyramine)
              • If tyramine were absorbed intact, it could lead to severe hypertension, including hypertensive crisis
              • Aged, fermented, cured, smoked, and pickled foods containing large amounts of exogenous amines (eg, aged cheese, pickled herring) may cause release of norepinephrine, resulting in a rise in blood pressure (tyramine reaction)
              • Avoid foods containing a large amount of tyramine while taking recommended ozanimod doses


            Pregnancy & Lactation


            Data are not available regarding use in pregnant women

            Based on animal studies, may cause fetal harm

            Animal studies

            • Adverse effects on development observed in offspring, including embryolethality, an increase in fetal malformations, and neurobehavioral changes, in the absence of maternal toxicity
            • In rabbits, fetal blood vessel malformations occurred at clinically relevant maternal ozanimod and metabolite exposures
            • The S1P receptor affected by ozanimod has been demonstrated to have an important role in embryogenesis, including vascular and neural development


            • Before initiating treatment, counsel females of childbearing potential regarding potential for serious fetal risks and the need for contraception during treatment and for 3 months after stopping ozanimod


            Data are not available on the presence in human milk, effects on breastfed infants, or effects on milk production

            Animal studies

            • Following oral administration, ozanimod and/or metabolites were detected in the milk of lactating rats at levels higher than those in maternal plasma

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.



            Mechanism of Action

            Sphingosine 1-phosphate (S1P) receptor modulator

            Binds with high affinity selectively to S1P subtypes 1 (S1P1) and 5 (S1P5); blocks lymphocyte egress from lymph nodes, reducing the number of lymphocytes in peripheral blood

            Mechanism by which ozanimod exerts therapeutic effects in MS is unknown, but may involve reduction of lymphocyte migration into the central nervous system


            Peak plasma time: 6-8 hr

            Peak plasma concentration

            • Ozanimod: 0.244 ng/mL (31.8%)
            • CC112273: 6.98 ng/mL (42.7%)


            • Ozanimod: 4.46 ngh/mL (31.8%)
            • CC112273: 143.77 ngh/mL (39.2%)

            Time to steady-state

            • Ozanimod: 102 hr (28.2%)
            • CC112273: 45 days (45%)

            Accumulation ratio

            • Ozanimod: 2.4 (21.1%)
            • CC112273: 16 (101%)


            Vd: 5590 L (ozanimod [27%])

            Protein bound

            • Ozanimod: 98.2%
            • CC112273: 99.8%
            • CC1084037: 99.3%


            Metabolized by multiple enzymes to form circulating major active metabolites (eg, CC112273, CC1084037) and several minor active metabolites (eg, RP101988, RP101075, RP101509) with similar activity and selectivity for S1P1 and S1P5

            Metabolized by ALDH/ADH to form carboxylate metabolite RP101988 and by CYP3A4 to form RP101075

            RP101075 is then metabolized either by NAT-2 to form RP101442 or by MAO-B to form CC112273

            CC112273 is then metabolized by CYP2C8 to form RP101509 or reduced to form CC1084037

            ~94% of circulating total active drug exposure is represented by ozanimod (6%), CC112273 (73%), and CC1084037 (15%)


            Clearance (ozanimod): 192 L/hr (37%)


            • Ozanimod: ~21 hr (15%)
            • CC112273 and its direct interconverting metabolite CC1084037: ~11 days (104%)


            • Primarily composed of inactive metabolites
            • Urine: ~26%
            • Feces: ~37%


            Oral Administration

            May take with or without food

            Avoid foods with high tyramine content (aged, fermented, cured, smoked, and pickled foods)

            Swallow capsule whole


            Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)





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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
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