• Home
  • A-B index
  • Pharmacological Index
  • Drug Classes
  • Active Ingredients
  • Companies
  • News
  • Arava
    / Sanofi

    Active Ingredient
    Leflunomide 10 mg, 20 mg

    Status in Israel

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    30 X 10 mg

    partial basket chart 27276 1649

    Film Coated Tablets

    30 X 20 mg

    partial basket chart 27277 1650

    Related information


    The treatment should be initiated and supervised by specialists experienced in the treatment of rheumatoid arthritis and psoriatic arthritis.
    Alanine aminotransferase (ALT) or serum glutamopyruvate transferase (SGPT) and a complete blood cell count, including a differential white blood cell count and a platelet count, must be checked simultaneously and with the same frequency:
    • before initiation of leflunomide,
    • every two weeks during the first six months of treatment, and
    • every 8 weeks thereafter (see section 4.4).
    In rheumatoid arthritis: leflunomide therapy is usually started with a loading dose of 100 mg once daily for 3 days. Omission of the loading dose may decrease the risk of adverse events. The recommended maintenance dose is leflunomide 10 mg to 20 mg once daily depending on the severity (activity) of the disease.
    In psoriatic arthritis: leflunomide therapy is started with a loading dose of 100 mg once daily for 3 days. The recommended maintenance dose is leflunomide 20 mg once daily.
    The therapeutic effect usually starts after 4 to 6 weeks and may further improve up to 4 to 6 months.
    There is no dose adjustment recommended in patients with mild renal insufficiency.
    No dose adjustment is required in patients above 65 years of age.
    Paediatric population: Arava is not recommended for use in patients below 18 years since efficacy and safety in juvenile rheumatoid arthritis (JRA) have not been established.
    Method of administration: Arava tablets are for oral use. The tablets should be swallowed whole with sufficient amounts of liquid. The extent of leflunomide absorption is not affected if it is taken with food.


    Arava is indicated in adults for the treatment of active rheumatoid arthritis (RA):
    1. to reduce signs and symptoms
    2. to inhibit structural damage as evidenced by X-ray erosions and joint space narrowing
    3. to improve physical function.
    Arava is indicated for the treatment of adult patients with active psoriatic arthritis.


    – Hypersensitivity (especially previous Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme) to the active substance, to the principal active metabolite teriflunomide or to any of the excipients.
    – Patients with impairment of liver function.
    – Patients with severe immunodeficiency states, e.g. AIDS.
    – Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia due to causes other than rheumatoid or psoriatic arthritis.
    – Patients with serious infections.
    – Patients with moderate to severe renal insufficiency, because insufficient clinical experience is available in this patient group.
    – Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.
    – Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with leflunomide and thereafter as long as the plasma levels of the active metabolite are above 0.02 mg/L. Pregnancy must be excluded before start of treatment with leflunomide.
    – Breast-feeding women.

    Special Precautions

    Concomitant administration of hepatotoxic or haematotoxic DMARDs “disease-modifying antirheumatic drug” (e.g. methotrexate) is not advisable.
    The active metabolite of leflunomide, A771726, has a long half-life, usually 1 to 4 weeks. Serious undesirable effects might occur (e.g. hepatotoxicity, haematotoxicity or allergic reactions), even if the treatment with leflunomide has been stopped. Therefore, when such toxicities occur or if for any other reason A771726 needs to be cleared rapidly from the body, the washout procedure has to be followed. The procedure may be repeated as clinically necessary.
    Liver reactions: Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide. Most of the cases occurred within the first 6 months of treatment. Cotreatment with other hepatotoxic medicinal products was frequently present. It is considered essential that monitoring recommendations are strictly adhered to.
    Haematological reactions: Together with ALT, a complete blood cell count, including differential white blood cell count and platelets, must be performed before start of leflunomide treatment as well as every 2 weeks for the first 6 months of treatment and every 8 weeks thereafter.
    Combinations with other treatments.
    Switching to other treatments.
    Skin reactions: In case of ulcerative stomatitis, leflunomide administration should be discontinued.
    Infections: It is known that medicinal products with immunosuppressive properties – like leflunomide – may cause patients to be more susceptible to infections, including opportunistic infections. Infections may be more severe in nature and may, therefore, require early and vigorous treatment. In the event that severe, uncontrolled infections occur, it may be necessary to interrupt leflunomide treatment and administer a washout procedure as described in the prescribing information.
    Lactose: Arava contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
    See prescribing information for full details.

    Side Effects

    The most frequently reported adverse effects with leflunomide are: mild increase in blood pressure, leucopenia, paraesthesia, headache, dizziness, diarrhoea, nausea, vomiting, oral mucosal disorders (e.g. aphthous stomatitis, mouth ulceration), abdominal pain, increased hair loss, eczema, rash (including maculo-papular rash), pruritus, dry skin, tenosynovitis, CPK increased, anorexia, weight loss (usually insignificant), asthenia, mild allergic reactions and elevation of liver parameters (transaminases (especially ALT), less often gamma-GT, alkaline phosphatise, bilirubin)).
    See prescribing information for full details.

    Drug interactions

    Increased side effects may occur in case of recent or concomitant use of hepatotoxic or haematotoxic medicinal products or when leflunomide treatment is followed by such medicinal products without a washout period.
    Therefore, closer monitoring of liver enzymes and haematological parameters is recommended in the initial phase after switching.
    See prescribing information for full details.

    Pregnancy and Lactation

    Pregnancy: The active metabolite of leflunomide, A771726 is suspected to cause serious birth defects when administered during pregnancy. Arava is contraindicated in pregnancy.
    Women of childbearing potential have to use effective contraception during and up to 2 years after treatment or up to 11 days after treatment.
    The patient must be advised that if there is any delay in onset of menses or any other reason to suspect pregnancy, they must notify the physician immediately for pregnancy testing, and if positive, the physician and patient must discuss the risk to the pregnancy. It is possible that rapidly lowering the blood level of the active metabolite, by instituting the drug elimination procedure described below, at the first delay of menses may decrease the risk to the foetus from leflunomide.
    Breast-feeding: Animal studies indicate that leflunomide or its metabolites pass into breast milk. Breast-feeding women must, therefore, not receive leflunomide.
    See prescribing information for full details.


    Symptoms: There have been reports of chronic overdose in patients taking Arava at daily doses up to five times the recommended daily dose, and reports of acute overdose in adults and children. There were no adverse events reported in the majority of case reports of overdose. Adverse events consistent with the safety profile for leflunomide were: abdominal pain, nausea, diarrhoea, elevated liver enzymes, anaemia, leucopenia, pruritus and rash.
    Management: In the event of an overdose or toxicity, colestyramine or charcoal is recommended to accelerate elimination. Colestyramine given orally at a dose of 8 g three times a day for 24 hours to three healthy volunteers decreased plasma levels of A771726 by approximately 40% in 24 hours and by 49% to 65% in 48 hours.
    Administration of activated charcoal (powder made into a suspension) orally or via nasogastric tube (50 g every 6 hours for 24 hours) has been shown to reduce plasma concentrations of the active metabolite A771726 by 37% in 24 hours and by 48% in 48 hours.
    These washout procedures may be repeated if clinically necessary.
    Studies with both hemodialysis and CAPD (chronic ambulatory peritoneal dialysis) indicate that A771726, the primary metabolite of leflunomide, is not dialysable.

    Sanofi Winthrop Industrie, France