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Leflunomide

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Leflunomide, Arava

  • See Also
  1. Disease Modifying Antirheumatic Drug
  2. Rheumatoid Arthritis
  • Indications
  1. Rheumatoid Arthritis
    1. First line DMARD instead of Methotrexate
    2. Has been used in combination with Methotrexate (but increased hepatotoxicity risk)
  2. Psoriatic Arthritis (off-label use)
  • Contraindications
  1. Hepatotoxicity risk factors including hepatic insufficiency
  2. Renal Insufficiency
  3. Severe Immunodeficiency
  4. Myelosuppression
  5. Serious infections
  • Mechanism
  1. Pyrimidine inhibitor
  2. T-Cell Activation and proliferation inhibitor
  3. Similar to Methotrexate in effects
  4. Onset of action in 1-2 months
  • Dosing
  1. Loading dose: 100 mg orally daily for 3 days
    1. Loading dose is avoided in most cases (rarely used)
    2. Loading dose increases adverse effects (e.g. hepatotoxicity)
    3. Most prescribers start with maintenance dosing
  2. Maintenance: 10 mg orally daily (or 20 mg orally every other day)
  3. Higher Dose (if inadequate relief at lower dose): 20 mg orally daily
  • Pharmacokinetics
  1. Half-Life: 18 days
  • Adverse Effects
  1. Nausea (may limit use)
  2. Alopecia
  3. Hepatotoxicity
    1. Liver injury occurs in 1 in 200 patients
    2. Increased Liver transaminases (e.g. AST, SGOT)
    3. Increased hepatotoxicity risk when combined with Methotrexate or Immunosuppressants
  4. Interstitial Lung Disease
    1. Lung injury (observe for new onset cough)
  5. Other rare, serious adverse effects
    1. Lymphoma
    2. Hematologic (Agranulocytosis, Pancytopenia, Thrombocytopenia)
    3. Stevens Johnson Syndrome
    4. Severe Hypertension
  6. Overdose or pregnancy detected
    1. See other references or contact poison control for protocol
    2. Administer Activated Charcoal 50 grams orally or by Nasogastric Tube every 6 hours for 24 hours
    3. Administer Cholestyramine 8 grams orally three times daily for up to 11 days
    4. May follow teriflunomide levels
      1. May direct repeat charcoal and Cholestyramine courses if levels >0.02 mg/L
  • Safety
  1. Avoid in Lactation
  2. Pregnancy Category X
    1. Avoid in pregnancy (Teratogenic)
    2. Screen for pregnancy before use and use reliable Contraception
  • Drug Interactions
  1. Warfarin
    1. Increases INR
  2. Drugs that increase Leflunomide levels
    1. Rifampin
  3. Drugs that decrease Leflunomide levels
    1. Cholestyramine
  • Monitoring
  1. Labs
    1. Aspartate Transaminase (SGOT, AST)
    2. Complete Blood Count with Platelet Count
  2. History
    1. Ask about new onset cough
  3. Timing
    1. Check monthly for 6 months
    2. Check every 6-8 weeks afterward
  • Efficacy
  1. Comparable to Methotrexate
  2. Used with Methotrexate for maximal effect
  • Resources
  1. Leflunomide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a48e6ef2-48ad-4fcf-9e67-dbba83ab0b79
  • References
  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Sharp (2000) Arthritis Rheum 43:495-505 [PubMed]