Ozanimod

ZEPOSIA 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. moderately to severely active ulcerative colitis (UC) in adults. 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.

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 S1P 2, S1P 3, and S1P 4. 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.

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.

ZEPOSIA is contraindicated in patients who: In the last 6 months, have experienced a myocardial infarction, unstable angina, stroke, transient ischemic attack (TIA), decompensated heart failure requiring hospitalization, or Class III or IV heart failure Have the 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 Have severe untreated sleep apnea Are taking a monoamine oxidase (MAO) inhibitor 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.

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 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: Obtain liver enzyme results before initiation and periodically during treatment.

The following serious adverse reactions are described elsewhere in the labeling: Infections Progressive Multifocal Leukoencephalopathy Bradyarrhythmia and Atrioventricular Conduction Delays Liver Injury Fetal Risk Increased Blood Pressure Respiratory Effects Macular Edema Cutaneous Malignancies Posterior Reversible Encephalopathy Syndrome Unintended Additive Immunosuppressive Effects from Prior Treatment with Immunosuppressive or Immune-Modulating Drugs Severe Increase in Multiple Sclerosis Disability after Stopping ZEPOSIA Immune System Effects after Stopping ZEPOSIA 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.

Tables 5 and 6 include drugs with clinically important drug and vaccine interactions when administered concomitantly with ZEPOSIA and instructions for preventing or managing them. Table 5: Clinically Relevant Interactions Affecting Drugs and Vaccines Co-administered with ZEPOSIA Anti-Neoplastic, Immune-Modulating, or Non-Corticosteroid Immunosuppressive Therapies Clinical Impact: ZEPOSIA has not been studied in combination with anti-neoplastic, immune-modulating, or non-corticosteroid immunosuppressive therapies with the exception of cyclosporine, which had no pharmacokinetic interaction. Prevention or Management: Caution should be used during concomitant administration because of the risk of additive immune effects during such therapy and in the weeks following administration.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).