Introduction
Zeposia (ozanimod) is a sphingosine 1-phosphate (S1P) receptor modulator approved by the FDA for the treatment of relapsing forms of multiple sclerosis (MS) and moderately to severely active ulcerative colitis. It represents an oral therapeutic option that offers both convenience and demonstrated efficacy in modulating immune cell trafficking.
Mechanism of Action
Zeposia acts as a sphingosine 1-phosphate (S1P) receptor modulator that binds with high affinity to S1P receptors 1 and 5. By binding to these receptors on lymphocytes, ozanimod prevents lymphocyte egress from lymph nodes, reducing the number of circulating lymphocytes in peripheral blood. This mechanism limits the migration of autoreactive lymphocytes into the central nervous system (in MS) or gastrointestinal tract (in ulcerative colitis), thereby reducing inflammatory activity.
Indications
- Relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
- Moderately to severely active ulcerative colitis in adults
Dosage and Administration
Initial titration (7-day regimen):- Day 1: 0.23 mg once daily
- Day 2: 0.23 mg once daily
- Day 3: 0.23 mg once daily
- Day 4: 0.46 mg once daily
- Day 5: 0.46 mg once daily
- Day 6: 0.46 mg once daily
- Day 7: 0.92 mg once daily (maintenance dose)
- Hepatic impairment: Not recommended in patients with severe hepatic impairment
- Renal impairment: No dosage adjustment necessary
- Elderly: Use with caution due to increased infection risk
Pharmacokinetics
Absorption: Time to peak concentration (Tmax): 6-8 hours; bioavailability: approximately 19% Distribution: Volume of distribution: 86 L; protein binding: 98% Metabolism: Extensive hepatic metabolism via multiple pathways including CYP2C8, CYP3A4, and other enzymes Elimination: Half-life: approximately 19 hours; primarily excreted in feces (57%) and urine (26%)Contraindications
- Patients with myocardial infarction, unstable angina, stroke, TIA, or decompensated heart failure within last 6 months
- History or presence of Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, or sino-atrial block
- Severe untreated sleep apnea
- Hypersensitivity to ozanimod or any component of the formulation
- Concomitant use with MAO inhibitors
Warnings and Precautions
Cardiovascular effects: May cause bradycardia and AV conduction delays. Requires cardiac monitoring during initiation Infections: Increased risk of infections, including opportunistic infections. Screen for infections before initiation Macular edema: May occur; ophthalmologic evaluation recommended in patients with diabetes or history of uveitis Liver injury: Monitor liver enzymes before and during treatment Respiratory effects: May cause decreased pulmonary function; use caution in patients with severe respiratory disease Fetal risk: May cause fetal harm; pregnancy should be excluded before initiation and effective contraception used Hypertension: Monitor blood pressure during treatment Malignancy risk: Potential increased risk of malignancies, including skin cancersDrug Interactions
Strong CYP2C8 inhibitors: May increase ozanimod exposure (avoid concomitant use) Strong CYP2C8 inducers: May decrease ozanimod efficacy (avoid concomitant use) Strong CYP3A4 inducers: May decrease ozanimod exposure (avoid concomitant use) MAO inhibitors: Contraindicated due to increased blood pressure risk Vaccines: Avoid live attenuated vaccines during and for 3 months after treatment QT-prolonging drugs: Potential additive effects on cardiac repolarizationAdverse Effects
Common (≥10%): Headache, hypertension, elevated liver transaminases, orthostatic hypotension, URI, dizziness, bradycardia Serious: Infections (including herpes zoster, cryptococcal infections), macular edema, liver injury, AV conduction abnormalities, respiratory effects, posterior reversible encephalopathy syndrome (PRES)Monitoring Parameters
- Complete blood count with differential (at baseline and during treatment)
- Liver function tests (at baseline, at 3 months, and periodically thereafter)
- Ophthalmologic evaluation (at baseline and if visual symptoms occur)
- Pulmonary function tests (if clinically indicated)
- Blood pressure and heart rate (especially during initiation)
- ECG (at baseline and if symptomatic bradycardia occurs)
- Infection monitoring throughout treatment
- Skin examination for malignancies
Patient Education
- Take medication exactly as prescribed at the same time each day
- Complete the full 7-day titration regimen as directed
- Report any signs of infection (fever, cough, unusual fatigue)
- Seek immediate medical attention for dizziness, palpitations, or shortness of breath
- Regular skin examinations recommended due to increased skin cancer risk
- Use effective contraception during treatment and for 3 months after discontinuation
- Inform all healthcare providers about Zeposia use before any vaccinations
- Do not stop medication abruptly without medical supervision
- Report any visual changes promptly
References
1. FDA prescribing information: Zeposia (ozanimod). Revised 2023 2. Cohen JA, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE). Lancet Neurol. 2019;18(11):1021-1033 3. Sandborn WJ, et al. Ozanimod as induction and maintenance therapy for ulcerative colitis. N Engl J Med. 2021;385(14):1280-1291 4. Kappos L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM). JAMA Neurol. 2019;76(9):1080-1090 5. Scott FL, et al. Ozanimod: A first-in-class sphingosine 1-phosphate receptor modulator for the treatment of ulcerative colitis and multiple sclerosis. Ann Pharmacother. 2022;56(5):592-603