LEFLUNOMIDE-WGR

What it is

LEFLUNOMIDE-WGR contains leflunomide 10 mg or 20 mg as the active ingredient per tablet. The 10 mg tablets are white and round, whilst the 20 mg tablets are yellow, round, with a scoreline on one side. Leflunomide is an isoxazole immunomodulatory agent that is rapidly metabolised to A771726, the active form, which has immunomodulating and immunosuppressive characteristics, acts as an anti-proliferative agent and displays weak anti-inflammatory properties.

Approved indications

— Active rheumatoid arthritis. — Active psoriatic arthritis.

Dosing overview

Leflunomide therapy is started with a loading dose of 100 mg once daily for three days. The recommended maintenance dose for rheumatoid arthritis is leflunomide 20 mg once daily. The recommended maintenance dose for psoriatic arthritis is 20 mg once daily. If dosing at 20 mg per day is not well tolerated, the dose may be decreased to 10 mg daily. An improvement in the patient's rheumatoid condition may begin as early as four weeks after starting therapy with leflunomide, however, there may be further improvement in the condition after four to six months of treatment.

Key safety warnings

Pancytopenia is a rare event which has been reported with leflunomide, with a fatal outcome in isolated cases, most frequently in cases of recent, concomitant or subsequent use of potentially myelotoxic agents such as methotrexate. A complete blood cell count should be performed in all patients before the start of leflunomide treatment and monthly for the first 6 months, followed by 6–8 weeks thereafter; if used with concomitant methotrexate or other potential immunosuppressives, chronic monitoring should be monthly. Very rare cases of severe liver injury, with fatal outcome in isolated cases, have been reported during treatment with leflunomide, with most cases occurring within the first 6 months of treatment. ALT and AST must be checked before the start of leflunomide treatment and monitored at monthly or more frequent intervals for at least the first 6 months and then, if stable, every 6–8 weeks thereafter; if leflunomide and methotrexate are given concomitantly, ALT, AST and serum albumin testing must be performed monthly. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and symptoms have been reported in patients treated with leflunomide; if a patient develops any of these skin conditions, therapy should be stopped and washout procedures should be initiated immediately. Interstitial lung disease has been reported rarely during treatment with leflunomide, with increased risk in patients with a history of interstitial lung disease; it is a potentially fatal disorder which may occur acutely, and new onset or worsening pulmonary symptoms such as cough and dyspnoea may be a reason for further investigation.

Contraindications

Patients with hypersensitivity to leflunomide, teriflunomide or to any of the excipients in the tablets; patients with severe immunodeficiency states, such as AIDS; patients with significantly impaired bone marrow function or significant anaemia, leukopenia or thrombocytopenia due to causes other than rheumatoid arthritis or psoriatic arthritis; patients with severe, uncontrolled infections; patients with impairment of liver function; pregnant women; women of childbearing potential who are not using reliable contraception during treatment with leflunomide and for a certain period of time thereafter, as long as the plasma levels of the active metabolite are above 0.02 mg/L, unless undergoing washout treatment; women who are breast-feeding; patients with severe hypoproteinaemia; and patients who have or have had Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme.

Regulatory history

LEFLUNOMIDE-WGR 10 mg and 20 mg tablets were first listed on the ARTG on 30 May 2024.