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Oral formulations of leflunomide

Drugs List

  • ARAVA 10mg tablets
  • ARAVA 20mg tablets
  • leflunomide 10mg tablets
  • leflunomide 15mg tablets
  • leflunomide 20mg tablets
  • Therapeutic Indications


    Active psoriatic arthritis
    Rheumatoid arthritis



    Therapy is 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 for patients with rheumatoid arthritis is 10 mg to 20 mg once daily, with the dose guided by disease severity.

    The recommended maintenance dose for patients with psoriatic arthritis is 20 mg once daily.

    Therapeutic effects should be expected after 4 to 6 weeks and continued improvements may occur up to 4 to 6 months.


    (See Dosage; Adult)

    Additional Dosage Information

    Washout procedure following leflunomide toxicity or when switching DMARD.

    One of the following washout procedures is recommended with duration being modified depending on clinical and laboratory results:

    1) cholestyramine 8 g given 3 times daily for 11 days.
    2) 50 g activated charcoal powder given 4 times daily for a period of 11 days.

    Washout procedure due to intended or confirmed pregnancy, males and females.

    After stopping treatment, one of the following washout procedures is recommended:

    1) cholestyramine 8 g given 3 times daily for 11 days.
    2) 50 g activated charcoal powder given 4 times daily for a period of 11 days.


    Children under 18 years
    Uncontrolled systemic infection
    Hepatic impairment
    Immunodeficiency syndromes
    Moderate renal impairment
    Severe anaemia
    Severe myelosuppression

    Precautions and Warnings

    Glucose-galactose malabsorption syndrome
    Interstitial lung disease
    Lactose intolerance
    Latent or healed tuberculosis

    Administration of live vaccines is not recommended
    Advise ability to drive/operate machinery may be affected by side effects
    Not all available strengths are licensed for all indications
    Treatment to be prescribed under the supervision of a specialist
    Contains lactose
    Some products may contain soya or soya derivative
    Exclude pregnancy prior to initiation of treatment
    Monitor blood pressure pre-treatment and periodically thereafter
    Monitor full blood count and differential WBC before and during therapy
    Monitor serum transaminases (including ALT) before and during therapy
    If no bleed at about monthly intervals,stop treatment. Exclude pregnancy
    Monitor patients with tuberculin reactivity
    Monitor regularly for frequency or severity of adverse events
    Refer women considering pregnancy for specialist advice and monitoring
    Consider colitis if patient presents with chronic diarrhoea
    Consider stopping treatment if severe uncontrolled infections occur
    Immunosuppressive drugs may increase risk of malignancy
    Long half life.Drug interactions possible weeks after treatment has stopped
    Serious adverse effects possible weeks after treatment stopped.
    May give falsely decreased values of ionised calcium
    Follow wash out procedure when switching between DMARDs eg methotrexate
    Pregnancy confirmed: Strongly consider washout procedure
    Consider discontinuing if pulmonary function becomes impaired
    Discontinue if ALT level exceeds 3 times the upper limit of normal
    Discontinue if severe haematological reactions including pancytopenia occur
    Discontinue if severe skin reaction occurs
    Discontinue if ulcerative stomatitis occurs
    Reduce dose or discontinue if a significant rise in hepatic enzymes occurs
    Advise patient to moderate alcohol intake during treatment
    Female: Contraception required during and for 2 years after treatment
    Male & female: Adequate contraception until metabolite level <0.02mg/litre
    Male: Contraception required during and for 3 months after treatment

    The active metabolite of leflunomide (A771726) has a long half life, usually 1 to 4 weeks and serious adverse effects may occur even after treatment withdrawal, such as hepatoxicity, haematotoxicity or allergic reactions. If such toxicities occur or when switching to another DMARD (e.g. methotrexate) a washout procedure should be performed.

    Women of child bearing potential must use effective contraception during and for up to 2 years after treatment cessation to allow the metabolite concentration to fall below 0.02 mg/litre. Although, a washout procedure may be instigated.

    Animal studies to evaluate the specific risk have not been conducted and there is no specific data on the risk of male-mediated foetal toxicity. However, to minimise any possible risk men wishing to father children should consider stopping leflunomide, undergoing the washout procedure and obtaining two separate plasma samples at least 14 days apart showing levels below 0.02 mg/litre and then waiting a further 3 months to ensure the risk of foetal toxicity is minimised.

    In patients with hypoproteinaemia the plasma level of the active metabolite (A771726) is expected to be increased as may for example occur in nephrotic syndrome.

    Ionised calcium levels may appear falsely decreased. Consider determining the total albumin adjusted serum calcium concentration.

    There are reported cases of severe liver injury, some with fatal outcome, usually during the first 6 months treatment with leflunomide. Concurrent hepatotoxic drugs were frequently involved and such combinations are not advised. In particular, hepatotoxic DMARDs (e.g. methotrexate) either concurrently or recently increase the risk of serious adverse hepatic reaction. It is, therefore, strictly essential that the monitoring recommendations are adhered to.

    Alanine aminotransferase (ALT) or serum glutamopyruvate transferase (SGPT) and a complete blood cell count, including differential white blood cell count and platelets, must be performed before the start of treatment, every 2 weekly intervals during the first six months of treatment and every 8 weeks thereafter. For ALT elevations between 2- and 3-fold the upper limit of normal, dose reduction to 10 mg may be considered with weekly monitoring required. Discontinue if ALT level persists at more than 2-fold the upper limit of normal or exceeds 3-fold the upper limit of normal. Wash-out procedures must then be initiated. Monitor hepatic enzymes after discontinuation of leflunomide until levels have normalised.

    Together with the hepatic monitoring carry out FBC, differential WBC and platelet monitoring before starting treatment, every 2 weeks for the first 6 months then every 8 weeks thereafter.

    In patients with pre-existing anaemia, leucopenia, and/or thrombocytopenia as well as in patients with impaired bone marrow function or at risk of bone marrow suppression, the risk of haematological reactions is increased. If such disorders occur, a washout to reduce plasma levels of the active metabolite (A771726) should be considered.

    Skin reactions:
    Very rare cases of Stevens-Johnson syndrome or toxic epidermal necrolysis have occurred, therefore, discontinue if severe skin reaction occurs. A complete washout is essential in these cases. A re-exposure to leflunomide is contraindicated.

    Switching treatment
    As leflunomide has a long persistence in the body, drug interactions and serious side effects are possible weeks after treatment has stopped if a washout procedure has not been performed.

    Recent or concurrent treatment with hepatotoxic or haemotoxic disease modifying antirheumatic drugs (e.g. methotrexate) may result in an increased risk of serious side-effects. Therefore the risks of treatment must be weighed against therapeutic benefit. If leflunomide is changed for another disease-modifying antirheumatic drug the washout procedure must be followed to reduce risks of serious side-effects. Concurrent therapy with disease-modifying antirheumatic drugs is not recommended.

    Peripheral neuropathy
    Patients aged older than 60 years, diabetes and concurrent neurotoxic medications may increase the risk for peripheral neuropathy.

    Pregnancy and Lactation


    Leflunomide is contraindicated during pregnancy.

    Leflunomide and its active metabolite are eliminated from the body very slowly and may take less than or equal to 2 years to reach active metabolite levels (less than 0.02 micrograms/ml) that are thought to have minimal risk based on animal data.

    Consult manufacturers information for details of washout procedures prior to planned pregnancy.

    Leflunomide has exhibited dose-related teratogenicity and embryo-foetal toxicity in animals at doses that resulted in systemic exposures at or below those obtained in humans.

    It is not known if leflunomide crosses the human placenta. the molecular weight (about 270) is low enough but the very low plasma concentrations suggest that exposure of embryo-foetus to leflunomide is minimal (Briggs, 2011).

    Treatment with leflunomide does not justify termination of pregnancy or any invasive diagnostic procedures. A detailed foetal ultrasound should be considered after treatment (Schaefer, 2007 ).

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( ) or if this is unavailable at the backup site ( ).


    Leflunomide is contraindicated during breastfeeding.

    The molecular weight of leflunomide of about 270 is low and its excretion into milk should be expected. There is positive evidence of risk to a breastfed infant or to breast milk production, but the actual effects of this drug on the nursing infant are unknown. Because of the potential for serious adverse effects to the nursing infant women taking this drug should not breastfeed (Briggs, 2011).

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at

    Side Effects

    Abdominal pain
    Acute hepatic necrosis (sometimes fatal)
    Allergic reaction
    Anaphylactic reaction
    Anaphylactoid reaction
    Aphthous stomatitis
    Cholestatic jaundice
    Collagenous colitis
    Creatine kinase increased
    Dry skin
    Erythema multiforme
    Hair loss
    Hepatic failure
    Increase in ALT level
    Increased susceptibility and severity of infections
    Increases in hepatic enzymes
    Interstitial lung disease
    Interstitial pneumonitis
    Lymphocytic colitis
    Maculopapular rash
    Microscopic colitis
    Mouth ulcers
    Peripheral neuropathy
    Progressive multifocal leukoencephalopathy (PML)
    Renal failure
    Spermatogenesis suppression
    Stevens-Johnson syndrome
    Taste disturbances
    Tendon rupture
    Toxic epidermal necrolysis
    Weight loss


    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( ) or if this is unavailable at the backup site ( ).

    Further Information

    Last Full Review Date: April 2014

    Reference Sources

    Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

    Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

    Martindale: The Complete Drug Reference, 37th edition (2011) ed. Sweetman, S. Pharmaceutical Press, London.

    Medications and Mothers' Milk, 14th Edition (2010) Hale, T. Hale Publishing, Amarillo, Texas.

    Summary of Product Characteristics: Arava 10 mg Tablets. Sanofi-Aventis. Revised November 2013.
    Summary of Product Characteristics: Arava 20mg Tablets. Sanofi-Aventis. Revised November 2013.
    Summary of Product Characteristics: Arava 100mg Tablets. Sanofi-Aventis. Revised November 2013.

    Summary of Product Characteristics: Leflunomide 10mg film-coated Tablets. Aspire Pharma Ltd. Revised June 2017.
    Summary of Product Characteristics: Leflunomide 20mg film-coated Tablets. Aspire Pharma Ltd. Revised June 2017.

    Summary of Product Characteristics: Leflunomide medac 10mg Tablets. Medac Gmbh. Revised July 2013.
    Summary of Product Characteristics: Leflunomide medac 15mg Tablets. Medac Gmbh. Revised July 2013.
    Summary of Product Characteristics: Leflunomide medac 20mg Tablets. Medac Gmbh. Revised July 2013.

    The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.

    NICE Evidence Services Available at: Last accessed: 13 July 2017

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