ozanimod (Rx)

Brand and Other Names:Zeposia
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 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

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

Dosage Modifications

Renal impairment

  • 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

Next:

Interactions

Interaction Checker

and ozanimod

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Upper respiratory tract infection (26%)

            1-10%

            Elevated hepatic transaminases (10%)

            Orthostatic hypotension (4%)

            Urinary tract infection (4%)

            Back pain (4%)

            Hypertension (4%)

            Upper abdominal pain (2%)

            <1%

            Macular edema

            Bradycardia

            Frequency Not Defined

            Hypersensitivity, including rash and urticaria

            Dose-dependent FEV1 and FVC reduction

            Previous
            Next:

            Warnings

            Contraindications

            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

            MAOIs

            Cautions

            Elevations of liver aminotransferases may occur

            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

            Sphingosine 1-phosphate (S1P) modulators associated with increased risk of macular edema; caution with history of uveitis or diabetes mellitus

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

            Severe exacerbation of disease, including disease rebound, has been rarely reported after discontinuation of a S1P receptor modulator

            Infections

            • Ozanimod causes 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, some serious in nature
            • Life-threatening and rare fatal infections have occurred in patients receiving ozanimod
            • Delay initiation in patients with an active infection until it is resolved
            • Consider interrupting treatment if serious infection develops
            • Because of ozanimod’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

            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

            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

            Contraception

            • 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

            Lactation

            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.

            Previous
            Next:

            Pharmacology

            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

            Absorption

            Peak plasma time: 6-8 hr

            Peak plasma concentration

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

            AUC

            • 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%)

            Distribution

            Vd: 5590 L (ozanimod [27%])

            Protein bound

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

            Metabolism

            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%)

            Elimination

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

            Half-life

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

            Excretion

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

            Administration

            Oral Administration

            May take with or without food

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

            Swallow capsule whole

            Storage

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

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            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
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.