leflunomide: clinical use

Prescribing considerations

• Initiation and supervision should be by a specialist experienced in rheumatoid arthritis.
• Before treatment, assess infection and tuberculosis risk, vaccination status, blood pressure, liver and marrow function, renal function, weight and pregnancy potential.
• Use a specialist-directed washout when rapid elimination is clinically required.
• Promptly review new pulmonary symptoms, peripheral neuropathy, persistent diarrhoea, skin ulceration or impaired wound healing.

Contraindications and cautions

• Hypersensitivity to leflunomide, teriflunomide or an excipient, including previous severe cutaneous reactions
• Hepatic impairment
• Severe immunodeficiency or serious infection
• Significant bone-marrow dysfunction or relevant cytopenias unrelated to rheumatoid arthritis
• Moderate-to-severe renal insufficiency
• Severe hypoproteinaemia
• Pregnancy, inadequate contraception where pregnancy is possible, or breastfeeding

Monitoring

• At baseline and regularly thereafter: full blood count with differential and platelets, liver tests including transaminases and albumin, blood pressure, renal function and weight.
• Increase monitoring when toxicity risk is higher or interacting hepatotoxic or haematotoxic treatment is used.
• Assess trends and individual abnormal results; discuss clinically significant changes with the specialist.

Clinical pharmacology

Leflunomide is rapidly converted to A771726, also called teriflunomide. This active, highly protein-bound metabolite inhibits dihydroorotate dehydrogenase and has a prolonged half-life because of slow clearance and enterohepatic recycling.

Formulation and product differences

• The selected product is a white, round, film-coated tablet containing lactose.
• Its score line assists breaking for swallowing but does not divide it into equal amounts.
• It may be supplied in blisters or bottles containing a desiccant; do not swallow the desiccant.

Tablet

Route: Oral

Strengths: 10 mg, 15 mg, 20 mg