Pharm

Dimethyl Fumarate

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Dimethyl Fumarate, Tecfidera

  • Background
  1. Generic in 2020
  • Indications
  1. Multiple Sclerosis (relapsing)
  • Mechanism
  1. Dimethyl Fumarate key effects
    1. Immunosuppressant that decreases CD8 T Cells as well as Cytokine production
    2. Dimethyl Fumarate effects are neuroprotective and immunomodulating
  2. Dimethyl Fumarate is orally Bioavailable
    1. Converted in vivo to active metabolite monomethyl fumarate (MMF)
  3. Monomethyl fumarate (MMF)
    1. MMF binds and activates nuclear factor erythroid 2 (NF-E2) and nuclear related factor 2 (Nrf2)
  4. Nuclear related factor 2 (Nrf2)
    1. Nrf2 on activation, translocates to the nucleus and binds antioxidant response element (ARE)
    2. Triggers a cascade of expression of cytoprotective genes
  • Medications
  1. Dimethyl Fumarate (Tecfidera) Delayed-release capsules: 120 mg and 240 mg
  • Dosing
  • Adults
  1. Start: 120 mg orally twice daily for 7 days
  2. Maintenance: 240 mg orally twice daily
    1. If not tolerated, may decrease dose to 120 mg orally twice daily for 4 weeks, then retrial higher dose
  • Adverse Effects
  1. Serious
    1. Anaphylaxis or Angioedema
    2. Progressive Multifocal Leukoencephalopathy (PML)
    3. Opportunistic infections (e.g. Herpes Zoster)
  2. Gastrointestinal
    1. Abdominal Pain
    2. Diarrhea
    3. Nausea
  3. Hematologic
    1. Lymphopenia
  4. Hepatotoxicity
    1. Elevated liver transaminases
  5. Cardiovascular
    1. Flushing (common)
      1. Decreases over time
      2. Consider taking with food and pretreating with Aspirin 30 min before dose
  • Safety
  1. Unknown safety in pregnancy
    1. Toxicity demonstrated in animals
  2. Unknown safety in Lactation
  3. Monitoring
    1. Complete Blood Count (at baseline and every 6 months)
    2. Liver Function Tests (at baseline and periodically)
    3. MRI Brain (for signs of PML)
      1. Consider yearly testing for JCV Antibodies
  • Efficacy
  1. Compared with other oral agents for MS
    1. Better tolerated than Fingolimod
    2. May be more effective than Teriflunomide
  • Resources
  1. Dimethyl Fumarate (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=6c42107a-2a42-4263-97b6-ae0d7675c92a