What are the side effects of Leflunomide (Arava)?

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Last updated: March 26, 2025View editorial policy

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From the Guidelines

Leflunomide's most common side effects include nausea, diarrhea, loss of appetite, weight loss, headache, and dizziness, while less frequent but more severe adverse reactions may include severe liver injury, pancytopenia, agranulocytosis, and thrombocytopenia. The side effects of leflunomide are a crucial consideration when prescribing this medication for the treatment of rheumatoid arthritis and psoriatic arthritis. According to the guidelines of care for the management of psoriasis and psoriatic arthritis 1, the most common side effects of leflunomide include gastrointestinal symptoms such as nausea, diarrhea, and loss of appetite, as well as weight loss, headache, and dizziness.

Serious Side Effects

More severe but less frequent side effects of leflunomide may include:

  • Severe liver injury, which can be fatal in some cases, with most cases occurring within 6 months of therapy and in patients with multiple risk factors for hepatotoxicity 1
  • Pancytopenia, agranulocytosis, and thrombocytopenia, which are rare but can occur in patients who have been treated with methotrexate or other immunosuppressive agents, or who have recently discontinued these medications 1
  • Elevated liver enzymes and leukopenia, which have been reported in clinical trials of leflunomide for the treatment of psoriasis and psoriatic arthritis 1

Monitoring and Preparing for Side Effects

To minimize the risk of side effects, regular monitoring of liver function and blood counts is recommended during treatment with leflunomide 1. This includes monthly CBC counts with differential and LFTs for the first 6 months and then every 6-8 weeks. Pregnancy testing is also recommended if indicated, as leflunomide is classified as a category X medication and should not be used by nursing mothers.

Clinical Considerations

It is essential to weigh the potential benefits of leflunomide against its potential risks and to closely monitor patients for signs of side effects. If you are experiencing side effects from leflunomide or need information about this medication, it is recommended that you consult with your healthcare provider for accurate information tailored to your situation.

From the FDA Drug Label

ADVERSE REACTIONS Adverse reactions associated with the use of leflunomide in RA include diarrhea, elevated liver enzymes (ALT and AST), alopecia and rash. WARNINGS Immunosuppression Potential/Bone Marrow Suppression Leflunomide is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe, uncontrolled infections. RARE CASES OF SEVERE LIVER INJURY, INCLUDING CASES WITH FATAL OUTCOME, HAVE BEEN REPORTED DURING TREATMENT WITH LEFLUNOMIDE Severe infections including sepsis, which may be fatal, have been reported in patients receiving leflunomide, especially Pneumocystis jiroveci pneumonia and aspergillosis. There have been rare reports of pancytopenia, agranulocytosis and thrombocytopenia in patients receiving leflunomide alone

The side effects of Leflunomide (Arava) include:

  • Diarrhea
  • Elevated liver enzymes (ALT and AST)
  • Alopecia
  • Rash
  • Severe liver injury
  • Severe infections (including sepsis, Pneumocystis jiroveci pneumonia, and aspergillosis)
  • Pancytopenia
  • Agranulocytosis
  • Thrombocytopenia 2 2 2

From the Research

Side Effects of Leflunomide (Arava)

The side effects of Leflunomide (Arava) include:

  • Nausea
  • Diarrhea
  • Hair fall
  • Liver toxicity
  • Peripheral neuropathy
  • Hypertension
  • Pneumonitis
  • Cytopenia 3
  • Allergic skin reactions
  • Toxic epidermal necrolysis (rare) 4
  • Diarrhea
  • Abnormalities in liver enzymes
  • Rash
  • Hypertension 5
  • Alopecia
  • Rash
  • Elevated liver enzymes
  • Allergic reaction
  • Asthenia
  • Abdomal pain
  • Back pain
  • Hypertension 6
  • Diarrhea
  • Nausea
  • Abnormal plasma liver enzyme levels 7

Rare but Serious Side Effects

Rare but serious side effects of Leflunomide (Arava) include:

  • Toxic epidermal necrolysis
  • Severe skin reactions
  • Liver toxicity
  • Peripheral neuropathy
  • Pneumonitis
  • Cytopenia 3, 4
  • Immunossuppression
  • Fetal death or teratogenic effects in pregnant women 6

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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