Leflunomide

What is Leflunomide?

Leflunomide is a disease-modifying antirheumatic drug (DMARD) that belongs to the class of immunomodulatory medications. It is primarily prescribed to treat rheumatoid arthritis and other autoimmune conditions by suppressing the overactive immune response that causes joint inflammation and damage. This oral medication works by targeting specific pathways in immune cell division and function.

Uses

• Rheumatoid arthritis: Primary indication for reducing joint pain, swelling, and preventing joint damage in adults with active disease
• Psoriatic arthritis: Used to control joint inflammation and skin symptoms in patients with this autoimmune condition
• Ankylosing spondylitis: May be prescribed for spinal inflammation when other treatments are inadequate
• Systemic lupus erythematosus: Sometimes used off-label as an alternative DMARD in certain cases
• Prevention of organ rejection: Occasionally used in transplant patients as an immunosuppressive agent

How it works

Leflunomide works by inhibiting dihydroorotate dehydrogenase, an enzyme essential for pyrimidine synthesis in rapidly dividing immune cells. By blocking this pathway, the drug prevents activated T-lymphocytes and other immune cells from multiplying and producing inflammatory substances that attack healthy joint tissue. This targeted approach helps reduce inflammation while allowing the immune system to maintain some protective functions.

Side effects

Common side effects:

• Diarrhea and nausea
• Hair loss or thinning
• Skin rash
• Headache
• Dizziness
• Elevated liver enzymes
• Weight loss
• Mouth ulcers

Serious side effects requiring immediate medical attention:

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• Severe liver damage or hepatitis
• Serious infections due to immune suppression
• Severe skin reactions including Stevens-Johnson syndrome
• Lung inflammation or scarring (interstitial pneumonitis)
• Severe peripheral neuropathy

Warnings and precautions

• Pregnancy and fertility: Leflunomide is contraindicated in pregnancy due to severe birth defect risks. Both men and women must use reliable contraception and may require drug elimination procedures before conception.
• Liver function monitoring: Regular liver function tests are essential as the drug can cause hepatotoxicity. Patients with pre-existing liver disease should avoid this medication.
• Infection risk: The immunosuppressive effects increase susceptibility to serious infections. Patients should be screened for tuberculosis and hepatitis before starting treatment.
• Blood pressure monitoring: Leflunomide can cause hypertension, requiring regular blood pressure checks and potential antihypertensive treatment.
• Vaccination considerations: Live vaccines should be avoided during treatment due to increased infection risk from immunosuppression.

Interactions

• Methotrexate: Increased risk of liver toxicity and bone marrow suppression when used together
• Warfarin: Leflunomide may enhance anticoagulant effects, requiring closer INR monitoring
• Rifampin: Can increase leflunomide blood levels, potentially leading to toxicity
• Cholestyramine: Dramatically reduces leflunomide levels and is used therapeutically for drug elimination
• Hepatotoxic medications: Alcohol and other liver-toxic drugs increase the risk of hepatotoxicity
• Live vaccines: Concurrent use may result in serious infections due to immune suppression
• Phenytoin: Leflunomide may increase phenytoin blood levels, requiring dose adjustments
• NSAIDs: May increase the risk of kidney problems when used long-term with leflunomide

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Dosage

For rheumatoid arthritis in adults, the typical starting dose is a loading dose of 100 mg once daily for three days, followed by a maintenance dose of 10-20 mg once daily. Some patients may start directly with the maintenance dose of 10-20 mg daily to reduce the risk of side effects. The exact dosage depends on individual patient factors including disease severity, tolerability, and response to treatment. Dosage adjustments may be necessary based on liver function tests and clinical response. All dosing decisions should be made by a qualified healthcare provider who can monitor for effectiveness and safety.

Sources: FDA DailyMed drug labels (public domain), BNF, WHO Essential Medicines List. This article is for informational purposes only and does not constitute medical advice. Always consult your healthcare provider before starting or stopping any medication.

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