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Leflunomide

Brand and Other Names: ARAVA
Mechanism of Action:

Leflunomide is an isoxazole immunomodulatory agent that inhibits dihydroorotate dehydrogenase (a mitochondrial enzyme involved in de novo pyrimidine synthesis) and has antiproliferative activity. Several in vivo and in vitro experimental models have demonstrated an anti-inflammatory effect.

Indications:

ARAVA is a pyrimidine synthesis inhibitor indicated for the treatment of adults with active rheumatoid arthritis.

Route: Oral
Dose:
  • Loading dosage for patients at low risk for ARAVA-associated hepatotoxicity and ARAVA-associated myelosuppression: 100 mg daily for 3 days.
  • Maintenance dosage: 20 mg daily.
    • Maximum recommended daily dosage: 20 mg once daily.
    • If 20 mg once daily is not tolerated, may decrease dosage to 10 mg once daily. 
  • Screen patients for active and latent tuberculosis, pregnancy test (females), blood pressure, and laboratory tests before starting ARAVA.
Adverse Reactions:

The most commonly reported adverse reactions (≥10%) regardless of relation to ARAVA treatment were diarrhea, respiratory infection, nausea, headache, rash, abnormal liver enzymes, and dyspepsia.

Contraindication:
  • Pregnancy.
  • Severe hepatic impairment.
  • Hypersensitivity to ARAVA or any of its inactive components.
  • Current teriflunomide treatment. 
Warnings and Precautions:

After stopping ARAVA, it is recommended that an accelerated drug elimination procedure be used to reduce the plasma concentrations of the active metabolite, teriflunomide. 

Severe infections (including sepsis), pancytopenia, agranulocytosis, and thrombocytopenia: Stop ARAVA and use accelerated elimination procedure. Do not start ARAVA in patients with active infection. 

Monitor CBCs during treatment with ARAVA.

Stevens-Johnson syndrome and toxic epidermal necrolysis, Drug reaction with eosinophilia and systemic symptoms (DRESS): Stop ARAVA and use accelerated elimination procedure. 

Peripheral neuropathy: If patient develops symptoms consistent with peripheral neuropathy, evaluate patient and consider discontinuing ARAVA. 

Interstitial lung disease: May be fatal. New onset or worsening symptoms may necessitate discontinuation of ARAVA and initiation of accelerated elimination procedure. 

Increased blood pressure: Monitor and treat. 

See package insert for full prescribing information.