Section 04 · Monograph

Ozanimod

Reviewed Nov 2026FDA label

ZeposiaS1P receptor modulator

Indications

Treatment of relapsing forms of multiple sclerosis (MS) in adultsFDA-labeled
Treatment of moderately to severely active ulcerative colitis in adultsFDA-labeled

Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator with high affinity for S1P receptor subtypes 1 and 5
Binding S1P1 receptors on lymphocytes causes internalization/degradation of the receptor, blocking lymphocyte egress from lymph nodes and secondary lymphoid tissues
Reduces the number of circulating lymphocytes available to recirculate to the CNS and (in ulcerative colitis) to the intestinal mucosa, decreasing inflammatory damage
S1P1 engagement on cardiac tissue is responsible for the transient dose-dependent decrease in heart rate observed with treatment initiation, mitigated by up-titration

Requires dose titration to reduce first-dose cardiac effects, using a 7-day starter pack
Days 1–4: 0.23 mg orally once daily
Days 5–7: 0.46 mg orally once daily
Day 8 and thereafter: 0.92 mg orally once daily (maintenance dose)
Pre-treatment assessment recommended: ECG, CBC, liver function tests, ophthalmic exam, and skin assessment
If ≥1–7 doses are missed depending on titration day, treatment must be reinitiated with the starter pack

Mild-to-moderate hepatic impairment: reduce maintenance dose to 0.92 mg every other day after titration; not recommended in severe hepatic impairment

Myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure requiring hospitalization within the last 6 months
Mobitz type II second-degree AV block, third-degree AV block, or sick sinus syndrome, unless patient has a functioning pacemaker
Severe untreated sleep apnea
Concurrent use of a monoamine oxidase inhibitor (MAOI)

Contraindicated with monoamine oxidase inhibitors; wait at least 14 days after stopping an MAOI before initiating ozanimod
Avoid concomitant strong CYP2C8 inhibitors (increases active metabolite exposure)
Avoid concomitant strong CYP2C8 inducers, including rifampin (decreases efficacy)
Avoid concomitant adrenergic and serotonergic drugs due to ozanimod's weak MAO-B inhibitory activity (risk of hypertensive crisis/serotonin toxicity), including certain OTC products (e.g., pseudoephedrine)
Live attenuated vaccines should be avoided during treatment and for 3 months after discontinuation
Concomitant heart-rate/AV-conduction-lowering drugs (e.g., beta-blockers) may have additive bradycardic effects

Baseline ECG before first dose (assess for pre-existing conduction abnormalities)
Baseline complete blood count (lymphocytes)
Baseline liver function tests, with periodic monitoring during treatment
Baseline ophthalmic (fundus) evaluation, especially in patients with diabetes or history of uveitis, and if visual symptoms occur
Baseline skin examination
Blood pressure monitoring during treatment
Monitor for signs/symptoms of infection; delay initiation if active infection is present
Monitor for symptoms suggestive of PML (progressive weakness, visual changes, cognitive/behavioral changes); withhold and evaluate if suspected
Assess pulmonary function (spirometry/DLCO) if clinically indicated

Animal studies showed embryolethality and fetal malformations at clinically relevant exposures
Women of reproductive potential should use effective contraception during treatment and for 3 months after stopping ozanimod
No human data on presence of ozanimod in breast milk; in animal studies, ozanimod/metabolites were present in rat milk at levels exceeding maternal plasma — weigh benefits of breastfeeding against potential infant risk