S1P Receptor Modulator (UC)
Pregnancy: Contraindicated — S1P modulator class associated with foetal harm (cardiac malformations in animal studies, analogous to fingolimod). Highly effective contraception required during treatment and for 3 months after stopping.
Ozanimod
Brand names: Zeposia
Adult dose
Dose: 0.23 mg days 1–4, 0.46 mg days 5–7, then 0.92 mg maintenance
Route: Oral
Frequency: Once daily
Max: 0.92 mg/day
Mandatory dose titration: 0.23 mg for 4 days, then 0.46 mg for 3 days, then 0.92 mg from day 8 onwards. Titration reduces first-dose cardiac effects. Source: BNF 90; MHRA SPC.
Paediatric dose
Dose: Not licensed under 18 years N/A/kg
Route: Oral
Frequency: N/A
Max: N/A
Not licensed for paediatric UC.
Dose adjustments
Renal
Severe renal impairment (eGFR <30 mL/min): use with caution — limited data. No dose adjustment for mild-moderate renal impairment.
Hepatic
Severe hepatic impairment (Child-Pugh C): contraindicated. Mild-moderate: no adjustment required.
Paediatric weight-based calculator
Not licensed for paediatric UC.
Clinical pearls
- TRUE NORTH trial (NEJM 2021): 18.4% clinical remission with ozanimod vs 6% placebo at week 10. Maintenance at week 52: 37% remission vs 18.5%. First oral S1P modulator approved for UC.
- MAO-B inhibition — the hidden interaction: ozanimod's major metabolite (CC112273) is a potent MAO-B inhibitor. Patients taking MAO inhibitors (including moclobemide, selegiline) must avoid ozanimod. Tyramine-rich foods (aged cheese, cured meats, red wine) may precipitate hypertensive crisis when combined.
- Mandatory ECG before first dose: AV block or bradycardia on baseline ECG requires cardiology review before starting. Dose titration is designed to minimise first-dose effect — do not skip titration steps.
- Macular oedema: rare but serious. Ophthalmological evaluation within 3–4 months of starting in patients with diabetes mellitus or history of uveitis. Blurred vision during treatment — stop and refer urgently.
- Lymphocyte count before starting: absolute lymphocyte count must be checked. Treatment should not be initiated if absolute lymphocyte count <0.5 × 10⁹/L. Monitor monthly for first 3 months. Source: BNF 90; MHRA SPC Zeposia.
Contraindications
- Myocardial infarction, unstable angina, stroke, TIA in previous 6 months
- Decompensated heart failure or NYHA Class III/IV
- Mobitz type II second-degree or third-degree AV block, sick sinus syndrome (without pacemaker)
- Severe hepatic impairment (Child-Pugh C)
- Active serious infection including TB
- MAO inhibitor use (including moclobemide) — see interactions
- Pregnancy — teratogenic (related to fingolimod risks in S1P class)
Side effects
- Bradycardia and first-degree AV block (during titration — reason for cardiac monitoring)
- Hypertension (paradoxically — via S1P2 effects on vascular smooth muscle)
- Lymphopenia (class effect — S1P receptor modulation retains lymphocytes in nodes)
- Macular oedema (rare — ophthalmological monitoring if diabetic or uveitis history)
- Elevated liver transaminases
- Nasopharyngitis, upper respiratory tract infections
- Headache, fatigue
Interactions
- MAO-B inhibitors (selegiline, rasagiline): ozanimod metabolite is MAO-B inhibitor — combined use increases pressor amine exposure. Dietary tyramine restriction recommended with concomitant MAO inhibitors — AVOID combining with MAO inhibitors.
- Antiarrhythmics (amiodarone, sotalol, digoxin): additive bradycardia and AV block risk — avoid or cardiac monitor intensively
- Beta-blockers: increased bradycardia risk during titration
- Live vaccines: contraindicated during treatment and for 3 months after stopping
- Immunosuppressants: additive lymphopenia and infection risk
Monitoring
- ECG before first dose (AV block, bradycardia exclusion)
- Blood pressure at baseline and periodically (hypertension risk)
- FBC including lymphocyte count (monthly first 3 months, then every 3 months)
- Liver function tests (ALT, AST) at baseline and months 1, 3, 6, 12, then annually
- Ophthalmological review at 3–4 months (or sooner if visual symptoms)
- Signs of infection throughout treatment
Reference: BNFc; BNF 90; Sandborn et al. NEJM 2021 (TRUE NORTH); NICE TA741 (ozanimod for UC); MHRA SPC Zeposia 2022. Verify against your local formulary and the latest BNF before prescribing.
Related
Curated clinical cross-links plus same-class fallbacks.