Makindo Medical Notes

⚠️ Key safety point: Leflunomide is a potent immunomodulatory DMARD used in rheumatoid and psoriatic arthritis. It requires regular FBC, LFT, and blood pressure monitoring due to risks of hepatotoxicity, cytopenia, and hypertension. Women and men must use effective contraception — the drug is teratogenic and persists for months due to its long half-life.

📘 About: Always check the BNF link here

• Increasingly used as a second-line DMARD after methotrexate or as an alternative if methotrexate is contraindicated.
• Can be combined with other DMARDs (e.g. hydroxychloroquine, sulfasalazine) in “triple therapy.”
• Requires careful shared care monitoring between rheumatology and primary care.

⚙️ Mechanism of Action

• Inhibits the mitochondrial enzyme dihydroorotate dehydrogenase, blocking de novo pyrimidine synthesis.
• This selectively suppresses activated T-lymphocyte proliferation and downstream cytokine production.
• Results in reduced autoimmune joint inflammation and slowing of erosive disease progression in rheumatoid arthritis.

🎯 Indications

• Rheumatoid arthritis (RA) — for disease control and prevention of joint damage.
• Psoriatic arthritis (PsA) — specialist use where conventional DMARDs are inadequate.

💊 Dosing (Adults)

• Loading dose: Leflunomide 100 mg once daily for 3 days.
• Maintenance: Leflunomide 10–20 mg once daily PO.
• Psoriatic arthritis: same regimen (100 mg for 3 days → 20 mg OD), under specialist supervision.
• Omit loading dose in patients with hepatic impairment or intolerance — start directly at maintenance dose.

⚠️ Contraindications

• Pregnancy and lactation — teratogenic.
• Severe hepatic impairment or active liver disease.
• Significant immunodeficiency or serious infection.
• Severe hypoproteinaemia or renal impairment.
• Pre-existing bone marrow suppression (low WCC or platelets).
• Previous tuberculosis — ensure screening before initiation.

💥 Side Effects

• GI upset: nausea, diarrhoea, oral ulcers.
• Myelosuppression: falling WCC, anaemia, or thrombocytopenia → monitor FBC.
• Hepatotoxicity: elevated ALT/AST — check LFTs regularly.
• Hypertension: monitor blood pressure regularly.
• Infection risk: due to immunosuppression; hold drug during significant infection.
• Peripheral neuropathy (rare) and alopecia may occur.

📊 Monitoring

• FBC and LFTs every 2 weeks for first 6 months, then monthly (or per local protocol).
• Monitor BP regularly — treat or withhold if uncontrolled hypertension develops.
• Screen for hepatitis B/C and TB before starting.

⚕️ Pharmacokinetics

• Converted to active metabolite A77 1726 with a half-life of 2–3 weeks due to enterohepatic recycling.
• Cholestyramine 8 g TDS for 11 days can accelerate elimination in case of toxicity or planned pregnancy (“washout” regimen).

🧠 Teaching Point

Leflunomide represents a modern shift from broad immunosuppression to targeted inhibition of lymphocyte metabolism. By blocking pyrimidine synthesis, it halts clonal expansion of activated T cells — reducing inflammation while sparing resting cells. Its long half-life underpins both its convenient dosing and the need for careful planning before conception or switching therapy.

📚 References

• BNF: Leflunomide
• NICE CKS: Rheumatoid Arthritis
• NICE NG100: Rheumatoid Arthritis in Adults — Management