What are the side effects of Arava (Leflunomide)?

From the Guidelines

Arava (leflunomide) can cause several serious side effects, including severe liver damage, lung inflammation, severe infections, low blood cell counts, and peripheral neuropathy, and should be used with caution and regular monitoring of liver function and blood cell counts, as recommended by the most recent guidelines 1. The most common side effects of Arava include:

• Nausea
• Diarrhea
• Loss of appetite
• Weight loss
• Headache
• Dizziness More serious side effects that require immediate medical attention include:
• Severe liver damage
• Lung inflammation (interstitial lung disease)
• Severe infections
• Low blood cell counts
• Peripheral neuropathy Arava can also cause birth defects, so it should not be used during pregnancy or by those planning to conceive, as indicated by its category X pregnancy rating 1. Regular blood tests are necessary to monitor liver function and blood cell counts while taking this medication, with monthly CBC and LFTs recommended for the first 6 months and every 6-8 weeks thereafter 1. Patients should report any unusual symptoms to their healthcare provider immediately, especially shortness of breath, yellowing of the skin or eyes, unusual bleeding or bruising, or severe skin reactions. The risk of side effects may increase with higher doses or when combined with other immunosuppressive medications, such as methotrexate, which can lead to an increased risk of hepatotoxicity 1. Some side effects may diminish over time as the body adjusts to the medication, but persistent or severe symptoms should always be evaluated by a healthcare provider.

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. Hepatotoxicity RARE CASES OF SEVERE LIVER INJURY, INCLUDING CASES WITH FATAL OUTCOME, HAVE BEEN REPORTED DURING TREATMENT WITH LEFLUNOMIDE

Common side effects of Arava (leflunomide) include:

• Diarrhea
• Elevated liver enzymes (ALT and AST)
• Alopecia
• Rash
• Immunosuppression and bone marrow suppression: increased risk of infections, including opportunistic infections, and severe infections such as sepsis
• Hepatotoxicity: rare cases of severe liver injury, including fatal outcomes 2
• Pancytopenia, agranulocytosis, and thrombocytopenia have been reported in patients receiving leflunomide alone or in combination with other immunosuppressive agents 2
• Interstitial lung disease has been reported in patients taking leflunomide 2

From the Research

Arava Side Effects

• Commonly reported adverse effects of leflunomide, the active ingredient in Arava, include:
  • Diarrhea
  • Nausea
  • Hepatotoxicity
  • Hypertension
  • Transient global hair loss 3
• Additional side effects may be associated with the medication, including:
  • Reversible alopecia areata (AA), which is not listed as an adverse effect in the leflunomide product monograph, but has been reported in several cases 3
  • Liver injury, which can be severe and is more common in women, with a higher mortality rate in Indian patients compared to US patients 4
• The characteristics and outcomes of leflunomide-induced liver injury can vary depending on the population, with Indian patients more likely to experience severe cutaneous adverse reactions (SCAR) and a shorter drug latency compared to US patients 4

Specific Side Effects

• Alopecia areata: a rare case of reversible AA associated with the use of leflunomide has been reported, with a literature review of three published similar cases 3
• Liver injury: 17 patients with leflunomide/teriflunomide hepatotoxicity from two large drug-induced liver injury (DILI) registries have been described, with differences in characteristics and outcomes between Indian and US patients 4