Leflunomide

Aka: Leflunomide, Arava

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II. 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)

III. Contraindications

  1. Hepatotoxicity risk factors including severe hepatic insufficiency
  2. Renal Insufficiency
  3. Severe Immunodeficiency
  4. Myelosuppression
  5. Serious infections
  6. Pregnancy

IV. 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

V. Dosing

  1. Start 20 mg orally once daily
  2. 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
  3. Maintenance: 10 mg orally daily (or 20 mg orally every other day)
  4. Higher Dose (if inadequate relief at lower dose): 20 mg orally daily

VI. Pharmacokinetics

  1. Half-Life: 18 days

VII. Adverse Effects

  1. Nausea (may limit use)
  2. Diarrhea
  3. Headache
  4. Alopecia
  5. 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
  6. Interstitial Lung Disease
    1. Lung injury (observe for new onset cough)
  7. Other rare, serious adverse effects
    1. Lymphoma
    2. Hematologic (Agranulocytosis, Pancytopenia, Thrombocytopenia)
    3. Stevens Johnson Syndrome
    4. Severe Hypertension
  8. 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

VIII. Safety

  1. Avoid in Lactation
  2. Pregnancy Category X
    1. Avoid in pregnancy (Teratogenic)
    2. Screen for pregnancy before use and use reliable Contraception

IX. Drug Interactions

  1. Warfarin
    1. Increases INR
  2. Drugs that increase Leflunomide levels
    1. Rifampin
  3. Drugs that decrease Leflunomide levels
    1. Cholestyramine

X. 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 baseline and then monthly for 6 months
    2. Check every 6-8 weeks afterward

XI. Efficacy

  1. Comparable to Methotrexate
  2. Used with Methotrexate for maximal effect

XII. Resources

  1. Leflunomide (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a48e6ef2-48ad-4fcf-9e67-dbba83ab0b79

XIII. References

  1. Hamilton (2020) Tarascon Pocket Pharmacopoeia
  2. Sharp (2000) Arthritis Rheum 43:495-505 [PubMed]

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Cost: Medications

leflunomide (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
LEFLUNOMIDE 10 MG TABLET Generic $0.44 each
LEFLUNOMIDE 20 MG TABLET Generic $0.50 each
FPNotebook does not benefit financially from showing this medication data or their pharmacy links. This information is provided only to help medical providers and their patients see relative costs. Insurance plans negotiate lower medication prices with suppliers. Prices shown here are out of pocket, non-negotiated rates. See Needy Meds for financial assistance information. GoodRx is another tool for finding lower drug prices.

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