Generic Name

Zeposia

Mechanism

Ozanimod acts as an *intermediate-acting* agonist of the S1P1 and S1P5 receptors.
• S1P1 modulation: Traps lymphocytes in secondary lymphoid organs, reducing peripheral trafficking to the central nervous system (CNS) in MS and to the gut mucosa in UC.
• S1P5 modulation: Contributes to remyelination and neuroprotection by promoting oligodendrocyte survival and myelin repair.
• Rapid receptor internalization followed by slow dissociation allows for dose‑dependent pharmacodynamics with minimal cardiovascular effects compared to older S1P modulators.

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Pharmacokinetics

• Route: Oral, tablet (0.92 mg).
• Absorption: Peak plasma concentration (Tmax) ~1–2 h after dosing; oral bioavailability ~35 % (first‑pass metabolism).
• Distribution: Protein binding ~98 %.
• Metabolism: Primarily CYP2C8 (≈70 %), CYP3A4 (≈20 %), and CYP2C9 (≈10 %). Oxidative biotransformation to active metabolites.
• Elimination: Half‑life 7–10 days; mainly renal (≈70 %) and hepatic (≈30 %).
• Drug interactions: Strong CYP3A4 inhibitors (e.g., ketoconazole) or inducers (e.g., rifampin) *may* alter exposure; adjust dosing accordingly.

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Indications

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Contraindications

• Contraindications:
• Known hypersensitivity to ozanimod or any excipients.
• Severe uncontrolled heart conditions (e.g., NYHA class III/IV heart failure).
• Pregnancy (Category B); use only if benefits outweigh risks.
• Warnings:
• Cardiac: Transient bradycardia or AV block in the first 3 days; cardiac monitoring required in the first week.
• Ophthalmologic: Risk of macular edema; baseline and periodic ophthalmologic exams recommended.
• Hepatic: Elevated ALT/AST >5× ULN – discontinue and re‑evaluate.
• Infection: Lymphopenia (≥20 % absolute lymphocyte count) increases opportunistic infection risk; monitor CBC regularly.
• Pregnancy/Breastfeeding: Limited data; avoid if possible.

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Dosing

• Initial Titration (Week 1–4):
• 0.23 mg once daily for 4 weeks to mitigate cardiac events.
• Maintenance (Week 5 onward):
• 0.46 mg once daily.
• Administration:
• Take orally with or without food; if taken on an empty stomach, 0.23 mg dose should be taken between 1–3 h before or after meals.
• Missed Dose: Skip the missed dose; do not double up the next dose.
• Discontinuation: No washout period required, but watch for rebound MS activity.

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Adverse Effects

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Monitoring

• Baseline: CBC with differential, CMP (including liver enzymes), pregnancy test (if applicable), ophthalmology exam, ECG.
• During therapy:
• CBC: every 4 weeks first year, then every 6–12 months.
• LFTs: every 4 weeks first year, then every 6–12 months.
• Cardiac: ECG at baseline, 3 days, and 4 weeks; repeat if symptoms develop.
• Ophthalmology: baseline, 6 months, then annually.
• Drug‑drug interactions: review concomitant CYP3A4 inducers/inhibitors at each visit.

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Clinical Pearls

• Titration is Key – Starting at 0.23 mg daily for 4 weeks greatly reduces the risk of first‑dose bradycardia.
• Use a “Cardio‑First” Monitor – A single ECG after the first dose can identify contraindicated cardiac conduction abnormalities early.
• Lymphocyte Guard – A sustained absolute lymphocyte count <0.5 × 10⁹/L mandates dose interruption; consider disease‑specific risk/benefit.
• Pregnancy Precautions – Even though ozanimod is Category B, it should be discontinued in early pregnancy if possible; partner contraception counseling is prudent.
• S1P‑5 Utility – For patients with progressive disease features, the neuroprotective effect via S1P5 may confer a modest benefit beyond lymphocyte sequestration.
• Combination therapy – Caution: concurrent use with other S1P modulators (e.g., fingolimod) not recommended owing to additive immune suppression.
• Rebound Phenomenon – Abrupt discontinuation can precipitate a flare; tapering or transitioning to another disease‑modifying therapy is advised.

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• Quick Reference Table

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• *For a detailed pharmacology review, consult the latest Label and ADA Guidelines on MS Management.*