From the Guidelines
Leflunomide can cause several side effects, including common adverse effects such as nausea, diarrhea, loss of appetite, weight loss, headache, and dizziness, as well as more severe but less common side effects like liver damage and bone marrow suppression. The most recent and highest quality study, published in 2020 1, provides guidance on the management of psoriasis with systemic nonbiologic therapies, including leflunomide. According to this study, the most common adverse effects of leflunomide include:
- Nausea
- Diarrhea
- Loss of appetite
- Weight loss
- Headache
- Dizziness More severe but less common side effects of leflunomide include:
- Severe liver injury, which may be fatal
- Pancytopenia, agranulocytosis, and thrombocytopenia, particularly in patients who have been treated with methotrexate or other immunosuppressive agents It is essential to monitor patients taking leflunomide regularly, with monthly complete blood counts and liver function tests for the first six months and every 6-8 weeks thereafter 1. Patients should also be advised to report any unusual symptoms promptly, particularly yellowing of the skin or eyes, unusual bleeding or bruising, persistent cough, or difficulty breathing. The medication has a very long half-life, so a cholestyramine washout procedure may be needed if serious side effects occur or if pregnancy is planned 1. Leflunomide carries a pregnancy category X rating, meaning it can cause birth defects and must be avoided during pregnancy 1.
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 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
- Commonly reported adverse effects of leflunomide 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
- Leflunomide-induced 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
- Characteristics of leflunomide-induced liver injury include:
- Hepatocellular injury
- Severe cutaneous adverse reaction (SCAR)
- Short drug latency
- Higher mortality rate, especially in women and younger patients 4