Leflunomide Zentiva (Leflunomide)

Leflunomide is a disease‑modifying antirheumatic drug (DMARD) that targets inflammatory pathways in autoimmune arthritis.

• Rheumatoid arthritis: reduces joint inflammation, slows structural damage, and improves functional ability.
• Psoriatic arthritis: alleviates joint pain and skin lesions, decreasing disease severity.
• Active rheumatoid arthritis unresponsive to methotrexate: provides an alternative oral DMARD option.

• Leflunomide is rapidly converted to its active metabolite teriflunomide, which selectively inhibits the mitochondrial enzyme dihydroorotate dehydrogenase. This inhibition blocks de novo pyrimidine synthesis, limiting proliferation of activated T‑lymphocytes and other immune cells, thereby dampening the autoimmune inflammatory response that drives joint damage in rheumatoid and psoriatic arthritis.

Leflunomide may cause a range of adverse reactions, which are categorized by frequency and severity.

Common Side Effects

• Diarrhea: mild to moderate gastrointestinal upset.
• Nausea and vomiting: occasional stomach discomfort.
• Alopecia: reversible hair thinning.
• Rash or pruritus: skin irritation.
• Elevated liver enzymes: mild transaminase increase.
• Hypertension: new or worsening high blood pressure.

Serious or Rare Side Effects

• Severe liver injury: hepatitis or hepatic failure.
• Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Bone marrow suppression: anemia, leukopenia, thrombocytopenia.
• Interstitial lung disease: cough, dyspnea, pulmonary infiltrates.
• Serious infections: opportunistic or bacterial infections.
• Teratogenic effects: fetal malformations if exposure occurs during pregnancy.

When prescribing Leflunomide, clinicians should observe several precautionary measures to minimise risk.

• Liver monitoring: perform baseline and periodic liver function tests.
• Blood pressure: check and control hypertension before and during therapy.
• Pregnancy avoidance: contraindicated in pregnancy; ensure effective contraception.
• Teratogenic risk: advise women of child‑bearing potential to use two reliable contraceptive methods.
• Infection vigilance: assess for active infections and delay initiation if present.
• Store at room temperature: keep below 25 °C in the original packaging, protected from moisture.

Leflunomide interacts with several medicines; some require avoidance while others need close monitoring.

Major Interactions (Avoid)

• Warfarin: increased anticoagulant effect and INR elevation.
• Methotrexate: additive bone‑marrow and hepatic toxicity.
• Live vaccines: heightened risk of severe infection.
• Strong CYP1A2 inhibitors (e.g., fluoroquinolones): raise teriflunomide plasma levels.

Moderate Interactions (Monitor Closely)

• Statins: potential for increased muscle toxicity.
• Oral contraceptives: reduced efficacy, consider alternative contraception.
• Antihypertensives: possible blood pressure changes.
• NSAIDs: may augment liver enzyme elevations.