ARAVA

What it is

ARAVA contains leflunomide , an active ingredient supplied as 10 mg or 20 mg tablets . Leflunomide is an isoxazole immunomodulatory agent that is rapidly metabolized in the body 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

ARAVA therapy is started with a loading dose of 100 mg once daily for three days . The recommended maintenance dose for rheumatoid arthritis is 20 mg once daily . The recommended maintenance dose for psoriatic arthritis is 20 mg once daily . Doses higher than 20 mg per day are not recommended . If dosing at 20 mg per day is not well tolerated, the dose may be decreased to 10 mg daily .

Key safety warnings

Pancytopenia is a rare event reported with leflunomide, with fatal outcomes in isolated cases, occurring most frequently with concomitant or recent use of potentially myelotoxic agents such as methotrexate . If evidence of pancytopenia appears on routine haematological monitoring, ARAVA should be stopped, a washout procedure should commence, and close haematological monitoring should continue until confirmed resolution . Very rare cases of severe liver injury with fatal outcome in isolated cases have been reported during treatment with leflunomide, occurring most frequently within the first 6 months of treatment . ALT and AST must be checked before starting ARAVA and monitored at monthly or more frequent intervals for at least the first 6 months, then 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 (DRESS) have been reported in patients treated with leflunomide; if a patient develops any of these skin conditions, therapy should be stopped and washout procedures initiated immediately .

Contraindications

ARAVA has multiple contraindications: hypersensitivity to leflunomide, teriflunomide or to any of the excipients ; severe immunodeficiency states, such as AIDS ; significantly impaired bone marrow function or significant anaemia, leukopenia or thrombocytopenia due to causes other than rheumatoid arthritis or psoriatic arthritis ; severe, uncontrolled infections ; impairment of liver function ; pregnancy ; women of childbearing potential not using reliable contraception during treatment and for a certain period of time thereafter ; breast-feeding ; severe hypoproteinaemia ; and prior history of Stevens-Johnson syndrome, toxic epidermal necrolysis or erythema multiforme .

PBS listing

ARAVA 10 mg tablets and 20 mg tablets are listed on the PBS with restriction and ex-manufacturer prices of A$10.15 and A$15.45 respectively .

Regulatory history

ARAVA was first registered on the ARTG on 11 October 1999, with both 10 mg and 20 mg tablet formulations listed in licence category RE . In September 2022, the PBAC recommended a change to the PBS restriction for severe active psoriatic arthritis and severe active rheumatoid arthritis, with the restriction type changing from Authority Required (Streamlined) to Restricted Benefit .