Drug information of ozanimod


Ozanimod is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults

:Dosage Forms and Strengths

Mechanism of effect

Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system. S1P can be expressed ubiquitously, playing an important role in regulating inflammation. S1P1R, S1P2R, and S1P3R receptors can be found in the cardiovascular, immune, and central nervous systems. S1P4R is found on lymphocytic and hematopoietic cells, while S1P5R expression is found only on the spleen (on natural killer cells) or in the central nervous system

Ozanimod is a selective modulator of S1P receptors and binds to S1P1R and S1P5R subtypes. The mechanism of action of ozanimod is not fully understood, but this drug likely reduces the migration of lymphocytes that usually aggravate the inflammation associated with MS


Ozanimod reduces circulating lymphocytes that cause the neuroinflammation associated with MS, reducing debilitating symptoms and, possibly, disease progression. During clinical trials, ozanimod reduced MS-associated brain volume loss in several regions. Ozanimod causes the sequestration of peripheral lymphocytes, reducing circulating lymphocytes in the gastrointestinal tract
After discontinuing Ozanimod 0.92 mg, the median time for peripheral blood lymphocytes to return to the normal range was 30 days, with approximately 90% of patients in the normal range within 3 months

Ozanimod may cause a transient decrease in heart rate on initiation of dosing. An up-titration schedule of Ozanimod 0.23 mg followed by doses of 0.46 mg, and 0.92 mg attenuates the magnitude of heart rate reductions


Peak plasma time: 6-8 hr

Vd: 5590 L
98.2% :Protein Bound

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

(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%


: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


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

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

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

Points of recommendation

:Oral Administration
May take with or without food
Avoid foods with high tyramine content (aged, fermented, cured, smoked, and pickled foods)
Swallow capsule whole

:Adverse Effects
  Upper respiratory tract infection, Elevated hepatic transaminases, Orthostatic hypotension, Urinary tract infection, Back pain, Hypertension, Upper abdominal pain, Macular edema, Bradycardia, Hypersensitivity including rash and urticaria, Dose-dependent FEV1 and FVC reduction

: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

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

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

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 level

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

Breast feeding warning

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

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