Leflugen (Leflunomide)

Leflunomide is a disease‑modifying antirheumatic drug (DMARD) used to treat inflammatory joint diseases.

• Rheumatoid arthritis: reduces joint damage, pain, and swelling, improving functional ability.
• Psoriatic arthritis: alleviates skin and joint symptoms, slowing disease progression.
• Inadequate response to other DMARDs: provides an alternative therapeutic option for patients whose disease remains active despite prior DMARD therapy.

• Leflunomide is rapidly converted to its active metabolite teriflunomide, which inhibits the mitochondrial enzyme dihydroorotate dehydrogenase. This blockade reduces de novo pyrimidine synthesis, limiting the proliferation of activated lymphocytes. By decreasing the supply of nucleotides required for DNA replication, the drug dampens the immune response that drives chronic inflammation in rheumatoid and psoriatic arthritis. The resulting immunomodulatory effect helps control disease activity and prevent structural joint damage.

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

Common Side Effects

• Diarrhea: loose stools or increased bowel movements.
• Nausea: feeling of sickness or urge to vomit.
• Headache: mild to moderate cranial pain.
• Hypertension: elevated blood pressure readings.
• Alopecia: thinning or loss of hair.
• Rash: skin redness or irritation.

Serious or Rare Side Effects

• Hepatotoxicity: elevated liver enzymes or liver injury.
• Severe infections: increased susceptibility to bacterial or viral infections.
• Pulmonary toxicity: interstitial lung disease or pneumonitis.
• Bone marrow suppression: anemia, leukopenia, or thrombocytopenia.
• Stevens‑Johnson syndrome: severe skin and mucous membrane reaction.
• Severe hypertension: hypertensive crisis requiring urgent care.

Before prescribing Leflunomide, clinicians should consider several precautionary measures to ensure patient safety.

• Liver function monitoring: assess baseline enzymes and repeat periodically.
• Blood pressure assessment: measure regularly, especially in patients with hypertension.
• Hepatic impairment avoidance: do not use in patients with severe liver disease.
• Pregnancy safety: avoid use during pregnancy due to potential fetal risk.
• Hematologic monitoring: perform complete blood counts to detect bone‑marrow suppression.
• Store at below 25°C: keep in the original packaging, protect from moisture and light.

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

Major Interactions (Avoid)

• Warfarin: may increase anticoagulant effect and INR.
• Methotrexate: combined use can heighten hepatotoxic risk.
• Teriflunomide (or other leflunomide‑related compounds): additive toxicity.

Moderate Interactions (Monitor Closely)

• Antihypertensives: leflunomide may reduce blood‑pressure‑lowering effect.
• Cholesterol‑binding resins (e.g., cholestyramine): can decrease teriflunomide exposure.
• Oral contraceptives: may reduce hormonal efficacy, requiring additional contraception.