Leflunomide Ratiopharm (Leflunomide)

Leflunomide is a disease‑modifying antirheumatic drug used in the management of inflammatory arthritis conditions.

• Rheumatoid arthritis: reduces disease activity, joint swelling and slows structural damage.
• Psoriatic arthritis: improves joint pain and skin lesions associated with the disease.
• Adult patients with active disease: provides long‑term disease‑modifying benefits when conventional therapy is insufficient.

• Leflunomide inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, a key step in de novo pyrimidine synthesis. By limiting pyrimidine availability, it suppresses proliferation of activated lymphocytes, particularly T‑cells, thereby reducing the immune‑mediated inflammation that drives joint damage in rheumatoid and psoriatic arthritis. The drug’s active metabolite, teriflunomide, retains this enzymatic inhibition and contributes to the overall immunomodulatory effect, leading to decreased cytokine production and reduced synovial inflammation.

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: occasional feeling of sickness.
• Elevated liver enzymes: transient increase in hepatic transaminases.
• Headache: mild tension‑type headaches.
• Hypertension: modest rise in blood pressure.
• Rash: non‑specific skin eruptions.

Serious or Rare Side Effects

• Severe liver injury: hepatitis or hepatic failure requiring monitoring.
• Bone marrow suppression: neutropenia, anemia or thrombocytopenia.
• Pulmonary toxicity: interstitial lung disease or pneumonitis.
• Severe cutaneous reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.
• Infections: opportunistic infections due to immunosuppression.

Before initiating Leflunomide therapy, several safety considerations should be reviewed.

• Pregnancy: contraindicated; drug is classified as pregnancy category X.
• Liver function: assess baseline hepatic enzymes and monitor regularly.
• Hematology: obtain complete blood count before treatment and during therapy.
• Infections: screen for active infections and avoid initiating in immunocompromised patients.
• Vaccinations: administer required live vaccines prior to starting therapy.
• Store at ambient temperature: keep below 25 °C in the original packaging, protected from moisture and light.

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

Major Interactions (Avoid)

• Methotrexate: combined use may increase hepatotoxic risk.
• Strong CYP1A2 inhibitors (e.g., fluvoxamine): can raise leflunomide plasma levels.
• Warfarin: may enhance anticoagulant effect, requiring close INR monitoring.

Moderate Interactions (Monitor Closely)

• Azathioprine: additive bone marrow suppression potential.
• Live vaccines: reduced efficacy and increased infection risk.
• Cholesterol‑lowering agents (statins): possible increase in muscle toxicity.