Leflunomide Eg (Leflunomide)

Leflunomide is a disease‑modifying antirheumatic drug (DMARD) that interferes with the immune system to control chronic inflammatory joint disorders, providing long‑term disease control.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriatic arthritis: alleviates skin and joint symptoms and helps prevent structural damage.
• Juvenile idiopathic arthritis (age ≥ 2 years): helps control joint inflammation in pediatric patients.
• Adult onset Still’s disease: may improve systemic symptoms and joint involvement.
• Systemic lupus erythematosus (off‑label): occasionally used to manage refractory arthritis manifestations.

• Leflunomide is converted in the body to its active metabolite teriflunomide, which selectively inhibits the mitochondrial enzyme dihydroorotate dehydrogenase. This inhibition blocks de novo pyrimidine synthesis, limiting the proliferation of activated T‑ and B‑lymphocytes. The resulting reduction in lymphocyte expansion dampens the autoimmune response that drives joint inflammation in rheumatoid and psoriatic arthritis.

Leflunomide may cause a range of adverse reactions, varying from mild to severe.

Common Side Effects

• Diarrhea: mild to moderate gastrointestinal upset.
• Nausea: feeling of sickness or urge to vomit.
• Elevated liver enzymes: increased ALT/AST indicating hepatic stress.
• Headache: occasional mild to moderate head pain.

Serious or Rare Side Effects

• Severe liver injury: hepatitis or hepatic failure requiring monitoring.
• Bone marrow suppression: anemia, leukopenia, or thrombocytopenia.
• Pulmonary toxicity: interstitial lung disease or pneumonitis.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.

When prescribing Leflunomide, clinicians should consider several safety precautions to minimize risks.

• Pregnancy: avoid use; teratogenic risk requires effective contraception.
• Liver function: assess baseline enzymes and monitor regularly.
• Hematology: perform complete blood count before treatment and during therapy.
• Infections: screen for latent tuberculosis and monitor for opportunistic infections.
• Renal impairment: adjust use cautiously in severe renal dysfunction.
• Store at ambient temperature: keep below 25 °C, retain in original container, protect from moisture.

Leflunomide can interact with other medicines, altering its efficacy or increasing toxicity.

Major Interactions (Avoid)

• Warfarin: increased anticoagulant effect, may raise INR.
• Methotrexate: additive hepatotoxicity risk.
• Rifampin: induces metabolism, reducing Leflunomide levels.

Moderate Interactions (Monitor Closely)

• Azathioprine: combined bone marrow suppression.
• TNF‑α inhibitors: potential for enhanced immunosuppression.
• Simvastatin: may increase statin plasma concentrations.