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Leflunomide

The information on this page is specific to the rheumatology indications for leflunomide and how it is used by Dr Suppiah in the New Zealand context

What is Leflunomide?

Leflunomide is an immunosuppressive Disease Modifying Anti Rheumatic Drug (DMARD). Leflunomide is used in the treatment of rheumatoid arthritis, psoriatic arthritis, peripheral joint problems in ankylosing spondylitis, granulomatosis with polyangiitis, giant cell arteritis, polymyalgia rheumatica and occasionally in SLE.  

The active metabolite is teriflunomide.  It normally takes 1-2 months to notice the benefit from leflunomide, but the peak effect my take up to 6 months.

Benefits of leflunomide

Leflunomide improves joint pain, joint swelling, and reduces joint damage in rheumatoid arthritis and psoriatic arthritis.   Its efficacy in reducing symptoms and signs of arthritis and preventing joint damage (based on x-ray scores) is similar to methotrexate when used on its own to treat rheumatoid arthritis.

Leflunomide is also effective at treating lots of other inflammatory conditions including certain forms of vasculitis.  It is a newer medication than methotrexate, and was historically more expensive so generally used as second line treatment.

In rheumatoid arthritis, leflunomide it is often added to methotrexate as combination therapy to improve the signs and symptoms of arthritis.  In combination the effect is better than either medication alone.  

How to take leflunomide

The standard dose is 10-20mg per day.   It can be taken with or without food.

Side effects

Up to 25% of patients get loose bowel motions or diarrhoea with this medication and is often the limiting factor. Reflux and nausea can occur in about 10%. Raised blood pressure can occur in up to 10%. Liver test abnormalities occur in a similar number.

Other serious side effects are rare but include peripheral neuropathy (numbness or pins and needles in the hands and feet), bone marrow suppression and lung inflammation. The risk of liver toxicity, bone marrow suppression and lung inflammation is increased when taken with methotrexate.

Leflunomide stays in the body for a long time - so side effects if they do occur may take several months to improve even if the medication is stopped. If the side effect is serious or disabling, then leflunomide can be washed out of the body using a bile acid sequestrant called cholestyramine.  

Alcohol

Alcohol increases the liver toxicity of leflunomide.

If you have no underlying liver problems, you can drink a maximum of 14 units of alcohol per week.  You should drink no more than 3 units in any one day (which is equivalent to about 2 small glasses of wine).  Ideally have 2-3 alcohol free days per week.

Monitoring

Blood tests to check kidney function, liver function and full blood count are needed every month for the first few months. If stable the frequency of testing can be extended to every 2-3 months.

Response to treatment is usually assessed every 2-3 months.

Pregnancy

You should not get pregnant or breastfeed if you are on leflunomide.  Women of child bearing age should have appropriate contraception in place prior to starting leflunomide.

If women on leflunomide want to become pregnant, they will need to stop the medication for 2 year prior to trying to conceive or will need to have it washed out with cholestyramine.   

It is unclear whether it is safe for males to father children whilst on leflunomide, but the standard advice is to have it washed out prior to trying to father children.  

Vaccination

Our recommendations for vaccines if you are on leflunomide are:

1. Influenza vaccine (yearly)
2. Vaccination against pneumococcal disease (Prevenar 13 and Pneumovax 23 - every 5 years)
3. Vaccination against haemophilus influenza b (Hiberix)
4. Vaccination against meningococcal disease (Menectra)

You should not have live vaccines whilst on leflunomide  (e.g.  MMR, yellow fever, typhoid).

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