Introduction
Ozanimod is an oral 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. As a selective S1P receptor modulator, ozanimod represents a novel therapeutic approach in immunomodulation with a distinct mechanism of action compared to other disease-modifying therapies.
Mechanism of Action
Ozanimod functions as a selective sphingosine 1-phosphate receptor modulator that binds with high affinity to S1P receptor subtypes 1 and 5. The drug modulates lymphocyte trafficking by binding to S1P receptors on lymphocytes, preventing their egress from lymph nodes. This results in reduced peripheral lymphocyte counts, particularly affecting autoreactive T and B cells that contribute to inflammatory processes in multiple sclerosis and ulcerative colitis. The selectivity for S1P1 and S1P5 receptors may contribute to a improved safety profile compared to non-selective S1P receptor modulators.
Indications
- Relapsing forms of multiple sclerosis in adults, 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: 0.23 mg once daily on days 1-4, 0.46 mg once daily on days 5-7 Maintenance dose: 0.92 mg once daily beginning on day 8 Special populations:- 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
- Administer with or without food
- Swallow capsules whole; do not crush, chew, or open
Pharmacokinetics
Absorption: Rapidly absorbed with Tmax of 6-8 hours; bioavailability approximately 90% Distribution: Volume of distribution 86 L; >99% protein bound, primarily to albumin Metabolism: Extensive hepatic metabolism via multiple pathways including CYP2C8, CYP3A4, MAO-A, and MAO-B Elimination: Half-life approximately 21 hours; primarily excreted in feces (63%) and urine (26%) Active metabolites: CC112273 and CC1084037 contribute to pharmacological activityContraindications
- Hypersensitivity to ozanimod or any component of the formulation
- Patients with myocardial infarction, unstable angina, stroke, TIA, decompensated heart failure requiring hospitalization, or Class III/IV heart failure within the last 6 months
- History or presence of Mobitz type II second-degree or third-degree AV block, sick sinus syndrome, or sino-atrial block, unless patient has a functioning pacemaker
- Severe untreated sleep apnea
- Concomitant use with MAO inhibitors
Warnings and Precautions
Cardiac effects: May cause bradycardia and AV conduction delays; requires cardiac monitoring during initiation Infections: Increased risk of infections; obtain recent CBC (including lymphocyte count) before initiation Macular edema: Recommended ophthalmologic evaluation in patients with diabetes or history of uveitis Liver injury: Monitor liver enzymes before initiation and during treatment Fetal risk: May cause fetal harm; effective contraception recommended Respiratory effects: May decrease pulmonary function; monitor in patients with respiratory disease Hypertension: Monitor blood pressure during treatment Malignancy risk: Potential increased risk of malignancies; skin cancer monitoring recommendedDrug Interactions
Strong CYP2C8 inhibitors: May increase ozanimod exposure; avoid concomitant use Strong CYP2C8 inducers: May decrease ozanimod exposure; monitor effectiveness MAO inhibitors: Contraindicated due to increased hypertensive risk Beta-blockers: May enhance bradycardic effect; use with caution 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, transaminase elevation, orthostatic hypotension, urinary tract infection, back pain Serious: Infections (including herpes zoster and cryptococcal infections), bradycardia, AV conduction delays, macular edema, liver injury, respiratory effects, hypertension Laboratory abnormalities: Lymphopenia, elevated liver enzymesMonitoring Parameters
- Complete blood count with differential (including lymphocyte count) at baseline and periodically
- Liver function tests at baseline, at 3 months, and periodically thereafter
- ECG at baseline and after first dose titration
- Blood pressure monitoring
- Ophthalmologic examination in high-risk patients
- Signs and symptoms of infection
- Skin examination for malignancy screening
- Pulmonary function tests in patients with respiratory disease
Patient Education
- Take medication exactly as prescribed; do not stop abruptly
- Report any signs of infection (fever, chills, body aches) immediately
- Inform all healthcare providers about ozanimod use before any procedures or vaccinations
- Use effective contraception during treatment and for 3 months after discontinuation
- Report visual changes, shortness of breath, dizziness, or irregular heartbeat
- Regular blood pressure monitoring recommended
- Avoid live vaccines during treatment
- Carry identification indicating ozanimod use
- Report any new skin lesions or changes in existing moles
References
1. FDA Prescribing Information: Zeposia (ozanimod) capsules 2. Cohen JA, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (RADIANCE): a multicentre, randomised, 24-month, phase 3 trial. Lancet Neurol. 2019;18(11):1021-1033. 3. Sandborn WJ, et al. Ozanimod induction and maintenance treatment for ulcerative colitis. N Engl J Med. 2016;374(18):1754-1762. 4. Kappos L, et al. Safety and efficacy of ozanimod versus interferon beta-1a in relapsing multiple sclerosis (SUNBEAM): a multicentre, randomised, minimum 12-month, phase 3 trial. Lancet Neurol. 2019;18(11):1009-1020. 5. Scott FL, et al. Ozanimod (RPC1063) is a potent sphingosine-1-phosphate receptor-1 (S1P1) and receptor-5 (S1P5) agonist with autoimmune disease-modifying activity. Br J Pharmacol. 2016;173(11):1778-1792. 6. ClinicalTrials.gov: Multiple phase 2 and 3 trials evaluating ozanimod in MS and UC