APO-LEFLUNOMIDE

What it is

APO-LEFLUNOMIDE is a tablet containing 10 mg or 20 mg of leflunomide as the active ingredient.

Approved indications —

Active Rheumatoid Arthritis — Active Psoriatic Arthritis

Dosing overview

APO-LEFLUNOMIDE therapy is started with a loading dose of 100 mg (five 20 mg tablets or ten 10 mg tablets) once daily for three days. Avoiding a loading dose may decrease the risk of adverse events if leflunomide is used in combination with methotrexate, particularly for patients at increased risk of haematological or hepatic toxicity. An improvement in the patient's rheumatoid condition may begin as early as four weeks after starting therapy with APO-LEFLUNOMIDE, however, there may be further improvement in the condition after four to six months of treatment.

Key safety warnings

APO-LEFLUNOMIDE treatment was associated with elevations of liver function tests, primarily ALT and AST. These effects were generally reversible. Most transaminase elevations were mild (≤ 2 × upper limit of normal) and usually resolved while continuing treatment. Very rare cases of severe liver injury, with fatal outcome in isolated cases, have been reported during treatment with APO-LEFLUNOMIDE. Most of the cases occurred within the first 6 months of treatment. ALT and AST must be checked before the start of APO-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. Pancytopenia is a rare event, which has been reported with APO-LEFLUNOMIDE, with a fatal outcome in isolated cases. These events have been reported most frequently in cases of recent, concomitant or subsequent use of potentially myelotoxic/haematotoxic agents, such as methotrexate. A complete blood cell count (including differential white blood cell count and platelets) should be performed in all patients before the start of APO-LEFLUNOMIDE treatment and monthly for the first 6 months, followed by 6–8 weeks thereafter. If used with concomitant methotrexate and/or other potential immunosuppressives, chronic monitoring should be monthly. Cases of Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and symptoms (DRESS) have been reported in patients treated with APO-LEFLUNOMIDE. If a patient taking APO-LEFLUNOMIDE 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 APO-LEFLUNOMIDE. The risk of its occurrence is increased in patients with a history of interstitial lung disease. New onset or worsening pulmonary symptoms, such as cough and dyspnoea, with or without associated fever, may be a reason for further investigation. Patients should be informed about the early warning signs of interstitial lung disease and asked to contact their physician as soon as possible if these symptoms appear or worsen during therapy.

Contraindications

APO-LEFLUNOMIDE is contraindicated in patients with hypersensitivity to leflunomide, teriflunomide or to any of the excipients in the tablets; patients with severe immunodeficiency states, for example 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 APO-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.

PBS listing

No source document contains information about PBS listing status or pricing for APO-LEFLUNOMIDE.

Regulatory history

APO-LEFLUNOMIDE was first listed on the ARTG on 22 December 2015, with two registered variants: leflunomide 10 mg tablets (ARTG 251992) and leflunomide 20 mg tablets (ARTG 251993).