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Sphingosine 1-Phosphate Receptor Modulator

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Sphingosine 1-Phosphate Receptor Modulator, S1P Receptor Modulator, Fingolimod, Fingolimod Hydrochloride, Gilenya, Siponimod, Mayzent, Ozanimod, Zeposia, Ponesimod, Ponvory

  • Background
  1. Expensive in 2022 (~$10,000/month)
  • Indications
  1. Multiple Sclerosis (relapsing)
    1. Fingolimod (Gilenya)
    2. Siponimod (Mayzent)
    3. Ozanimod (Zeposia)
    4. Ponesimod (Ponvory)
  2. Ulcerative Colitis (active, moderate to severe)
    1. Ozanimod (Zeposia)
  • Contraindications
  1. Cardiovascular event in last 6 months (e.g. MI, CVA)
  2. Unstable Angina
  3. Atrioventricular Block
  4. Decompensated Congestive Heart Failure (stage 3-4)
  5. Antiarrhythmic use (Class Ia or class III)
  6. QTc Prolongation >500 msec
  • Mechanism
  1. Acts as an Immunosuppressant, decreasing Lymphocyte migration to the Central Nervous System
  2. Sphingosine-1-phosphate receptor blocker (S1P Receptor)
    1. Blockade results in fewer Lymphocytes exiting Lymph Nodes
    2. Decreases autoimmune attack of Myelin Sheath
  • Medications
  1. Fingolimod (Gilenya)
    1. Adult: 0.5 mg orally daily
    2. Child (age >=10 years)
      1. Weight >40 kg: Use adult dose
      2. Weight <40 kg: 0.25 mg orally daily
  2. Siponimod (Mayzent)
    1. Released in 2020 and similar to Fingolimod
    2. Dosing is adjusted for specific CYP2C9 Genotypes (contraindicated in some Genotypes, test before administration)
  3. Ozanimod (Zeposia)
    1. Released in 2020 and similar to Fingolimod
    2. Dose 0.92 mg orally once daily (see references for dosing adjustments)
  4. Ponesimod (Ponvory)
    1. Released in 2021 and similar to Fingolimod
    2. Dose 20 mg orally once daily (see references for dosing adjustments)
  • Adverse Effects
  1. Cardiovascular
    1. Hypertension
    2. QTc Prolongation
    3. Bradycardia
      1. May present with Dizziness or Fatigue
      2. Observe for 6 hours after first dose (or after restarting Fingolimod with last dose >14 days)
      3. Avoid in those with known Arrhythmia or other heart disorder
      4. Avoid concurrent use with Digoxin, Diltiazem or Beta Blocker
  2. Hepatotoxicity
    1. Elevated liver transaminases
  3. Uncommon but Serious Adverse Effects
    1. Melanoma
    2. Macular edema
    3. Serious infections
    4. HSV Encephalitis
    5. Progressive Multifocal Leukoencephalopathy (PML)
      1. Onset within 12 to 24 months of Fingolimod
      2. Consider JC Virus Antibody testing
      3. Obtain MRI Brain for new neurologic changes
  • Safety
  1. Unknown safety in pregnancy
  2. Unknown safety in Lactation
  3. Monitoring
    1. Complete Blood Count (baseline and periodically)
    2. Ophthalmology for dilated Eye Exam (baseline and after 3-4 months)
    3. Liver Function Tests (baseline)
  • Drug Interactions
  1. Live Vaccines
    1. Avoid while using Fingolimod and for at least 2 months after
    2. Update Vaccinations (including VZV Vaccine) at least 2 months before treatment
  2. CYP2C9 Inhibitors or Inducers
    1. Siponimod (Mayzent) requires testing for CYP2C9 Genotype before use
  • Resources
  1. Fingolimod (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=cc9e1c8c-0e2b-44e2-878b-27057f786be9
  2. Siponimod (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=44492772-5aed-4627-bd85-e8e89f308bb3
  3. Ozanimod (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=93ce2fab-edfb-4804-8074-963071de51e4
  4. Ponesimod (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5be69660-738c-4db7-b0d4-517aa873dc41