Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. Ozanimod blocks the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in peripheral blood. Ozanimod has minimal or no activity on S1P2, S1P3, and S1P4. The mechanism by which ozanimod exerts therapeutic effects in multiple sclerosis and ulcerative colitis is unknown but may involve the reduction of lymphocyte migration into the central nervous system and intestine.

ZEPOSIA is a sphingosine 1-phosphate receptor modulator 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. 
• Moderately to severely active ulcerative colitis (UC) in adults.

• Assessments are required prior to initiating ZEPOSIA.
• Titration is required for treatment initiation. 
• The recommended maintenance dosage is 0.92 mg orally once daily. 
• The recommended maintenance dosage in patients with mild or moderate chronic hepatic impairment (Child-Pugh class A or B) is 0.92 mg once every other day.
• If a dose is missed within the first 2 weeks of treatment, reinitiate with the titration regimen. If a dose is missed after the first 2 weeks of treatment, continue treatment as planned.

Most common adverse reactions (incidence ≥4%) are:

• Multiple Sclerosis: upper respiratory infection, hepatic transaminase elevation, orthostatic hypotension, urinary tract infection, back pain, and hypertension.
• Ulcerative Colitis: liver test increased, upper respiratory infection, and headache.

• In the last 6 months, experienced myocardial infarction, unstable angina, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or Class III or IV heart failure.
• Presence of Mobitz type II second-degree or third degree atrioventricular (AV) block, sick sinus syndrome, or sino-atrial block, unless the patient has a functioning pacemaker.
• Severe untreated sleep apnea.
• Concomitant use of a monoamine oxidase inhibitor.

• Infections: ZEPOSIA may increase the risk of infections. Obtain a complete blood count (CBC) before initiation of treatment. Monitor for infection during treatment and for 3 months after discontinuation. Do not start ZEPOSIA in patients with active infections.
• Progressive Multifocal Leukoencephalopathy (PML): Withhold ZEPOSIA at the first sign or symptom suggestive of PML.
• Bradyarrhythmia and Atrioventricular Conduction Delays: ZEPOSIA (ozanimod) may result in transient decrease in heart rate; titration is required for treatment initiation. Check an electrocardiogram (ECG) to assess for preexisting cardiac conduction abnormalities before starting ZEPOSIA. Consider cardiology consultation for conduction abnormalities or concomitant use with other drugs that decrease heart rate.
• Liver Injury: Discontinue if significant liver injury is confirmed. Obtain liver function tests before initiating ZEPOSIA. 
• Fetal Risk: Women of childbearing potential should use effective contraception during treatment and for 3 months after stopping ZEPOSIA.
• Increased Blood Pressure (BP): Monitor BP during treatment.
• Respiratory Effects: May cause a decline in pulmonary function. Assess pulmonary function (e.g., spirometry) if clinically indicated.
• Macular Edema: A prompt ophthalmic evaluation is recommended if there is any change in vision while taking ZEPOSIA. Diabetes mellitus and uveitis increase the risk of macular edema; patients with a history of these conditions should have an ophthalmic evaluation of the fundus, including the macula, prior to treatment initiation.