Leflunomide Milpharm (Leflunomide)

Leflunomide is a disease‑modifying antirheumatic drug that acts on inflammatory pathways in autoimmune arthritis.

• Rheumatoid arthritis: reduces disease activity, slows joint damage, and improves functional ability.
• Psoriatic arthritis: alleviates joint inflammation and can improve associated skin lesions.
• Inadequate response to methotrexate: provides an alternative disease‑modifying option for patients who have not responded adequately to first‑line therapy.

• Leflunomide inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, which blocks de novo pyrimidine synthesis. This limits the proliferation of activated lymphocytes, thereby reducing the autoimmune inflammatory response that drives joint damage in rheumatoid and psoriatic arthritis.

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

Common Side Effects

• Diarrhoea: mild to moderate gastrointestinal upset.
• Nausea: occasional feeling of sickness.
• Alopecia: reversible hair thinning.
• Rash: skin irritation or erythema.
• Elevated liver enzymes: mild hepatic enzyme rise.
• Hypertension: increase in blood pressure.

Serious or Rare Side Effects

• Severe liver injury: potential hepatic failure.
• Stevens‑Johnson syndrome: rare severe skin reaction.
• Bone marrow suppression: pancytopenia or anemia.
• Interstitial lung disease: pulmonary inflammation.
• Severe infection: opportunistic infections due to immunosuppression.
• Teratogenicity: risk of fetal malformations.

Before initiating therapy, clinicians should assess baseline health and monitor patients regularly.

• Pregnancy: contraindicated (Category X); effective contraception required.
• Liver function: obtain baseline tests and monitor periodically.
• Hematology: perform regular complete blood counts to detect cytopenias.
• Infection risk: evaluate for active infections and avoid live vaccines.
• Store below 25°C: keep in the original pack, protect from moisture.

Leflunomide can interact with several medicines, requiring careful management.

Major Interactions (Avoid)

• Warfarin: may increase INR and bleeding risk.
• Strong CYP1A2 inhibitors (e.g., fluconazole): raise leflunomide plasma levels.
• Cholesterol‑binding resins (e.g., cholestyramine): markedly reduce drug exposure.

Moderate Interactions (Monitor Closely)

• Methotrexate: additive hepatotoxicity; monitor liver enzymes.
• NSAIDs: increased risk of liver injury.
• Statins: heightened chance of myopathy; observe muscle symptoms.