Leflunomide Ratiopharm (Leflunomide)

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

• Rheumatoid arthritis: reduces joint inflammation and slows radiographic progression.
• Psoriatic arthritis: improves skin and joint symptoms while limiting disease progression.
• Inadequate response to conventional DMARDs: offers an alternative mechanism of action for patients not achieving control with first‑line therapy.

• Leflunomide inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, which is essential for de novo pyrimidine synthesis. By blocking pyrimidine production, the drug reduces proliferation of activated lymphocytes, thereby dampening the autoimmune response that drives joint inflammation and tissue damage.

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

Common Side Effects

• Diarrhea: loose stools, often mild.
• Nausea: occasional stomach upset.
• Alopecia: thinning or loss of hair.
• Rash: skin irritation or erythema.
• Elevated liver enzymes: mild transaminase rise.
• Hypertension: increase in blood pressure.

Serious or Rare Side Effects

• Severe liver injury: hepatitis or hepatic failure.
• Stevens‑Johnson syndrome: severe skin and mucosal reaction.
• Bone marrow suppression: anemia, leukopenia, or thrombocytopenia.
• Pulmonary toxicity: interstitial lung disease.
• Serious infections: opportunistic or severe bacterial infections.
• Teratogenicity: risk of fetal malformations.

Before initiating therapy, several precautions should be considered.

• Liver function monitoring: check transaminases before start and regularly thereafter.
• Blood pressure assessment: monitor and manage hypertension during treatment.
• Pregnancy avoidance: use effective contraception; drug is contraindicated in pregnancy.
• Breastfeeding caution: avoid use while nursing due to unknown safety.
• Infection vigilance: screen for active infections and delay therapy if present.
• Renal impairment dose adjustment: consider reduced dose in moderate to severe renal dysfunction.
• Store at room temperature: keep in original packaging, protect from moisture and light.

Leflunomide can interact with other medicines, influencing efficacy or safety.

Major Interactions (Avoid)

• Warfarin: increased anticoagulant effect, risk of bleeding.
• Teriflunomide: additive toxicity, especially hepatic.
• Live vaccines: heightened risk of infection; avoid concurrent use.
• Azathioprine: combined bone marrow suppression.
• Strong CYP3A4 inducers (e.g., rifampin): may reduce leflunomide exposure.

Moderate Interactions (Monitor Closely)

• Methotrexate: potential additive hepatotoxicity.
• Statins: increased risk of myopathy.
• Antihypertensives: possible reduced efficacy.
• Oral contraceptives: decreased hormonal effectiveness.
• Allopurinol: may increase leflunomide plasma levels.