Leflunomide

What is leflunomide?

Leflunomide (brand names: Arabloc®, Arava®, Lunava®) is a medicine used to treat rheumatoid arthritis and psoriatic arthritis.

It is an immunosuppressive medicine, which means that it works by reducing the activity of the immune system.

In rheumatoid and psoriatic arthritis this action helps to reduce inflammation and thus reduces pain and swelling in the joints. It also limits damage to the joints and helps to prevent disability in the long term.

Because leflunomide acts to reduce the damage to the joints, rather than just relieve the pain, it belongs to the group of medicines called disease modifying antirheumatic drugs (DMARDs).

What benefit can you expect from your treatment?

Over 70% of people treated with leflunomide experience improvement of their rheumatoid arthritis. Some achieve remission, where the arthritis virtually disappears. As with many medicines used to treat rheumatoid arthritis, some people experience no benefit from leflunomide treatment.

Leflunomide does not work straight away. It usually takes 4 to 8 weeks for symptoms to start to improve. The full effect may take up to 26 weeks.

Other medicines may be given to improve your symptoms while waiting for the leflunomide to work.

How is leflunomide taken?

Leflunomide is taken by mouth in tablet form. The usual dose is 10mg or 20mg once daily. Sometimes a higher dose may be given to begin with, but side effects are more common with this approach.

The tablets should be swallowed whole, not chewed or broken. They can be taken with or without food.

Leflunomide may be used with other arthritis medicines including:

  • other DMARDs such as methotrexate
  • biological DMARDs (a newer type of DMARD, which act on natural substances in the body that contribute to inflammation and joint damage)
  • steroid medicines such as prednisolone or cortisone injections into the joint
  • anti-inflammatory medicines (NSAIDs) such as naproxen (Naprosyn) or ibuprofen (Brufen, Nurofen)
  • simple pain medicines such as paracetamol.

How long is the treatment continued?

Treatment with leflunomide can be continued for more than 10 years as long as it is effective and no serious side effects occur.

If leflunomide treatment is stopped for more than a few weeks there is a risk that your condition will worsen. Continue with your treatment unless advised by your doctor or unless side effects develop.

Are there any side effects?

You might experience side effects with your treatment. Tell your doctor if you are concerned about possible side effects.

If you do experience side effects, a reduction in dose may minimise these so that you can continue to take the medicine. Your doctor will advise on any dose changes that are necessary.

Most common possible side effects

  • Leflunomide may cause a dry mouth or mouth ulcers
  • Up to 20% of people experience stomach and bowel side effects when taking leflunomide. These effects can include excessive wind, bowel discomfort, loss of appetite, nausea (feeling sick) and diarrhoea. They often lessen after a few weeks of treatment; they may be reduced by drinking plenty of water.
  • Up to 10% of people may have other common side effects such as skin rashreversible thinning of hair, increase in blood pressure or dizziness. These side effects are not usually serious and may lessen with continued treatment.

Less common or rare possible side effects

There are some rare but potentially serious side effects with leflunomide. These are more likely if leflunomide is being taken with methotrexate.

  • Blood counts: Leflunomide can cause a drop in the number of white blood cells, which are needed to fight infection. It can also cause a drop in the number of platelets, which help to stop bleeding. Regular blood tests aim to pick these problems up early when they occur. However, if you develop a sore mouth, mouth ulcers, easy bruising, nosebleeds, bleeding gums, breathlessness, infection or fever, tell your doctor straight away.
  • Infections: There is an increased risk of developing some infections, especially herpes zoster (chicken pox and shingles). You should try to avoid contact with people who have these infections. If you have an infection, persistent fever or symptoms of COVID-19, tell your doctor straight away.
  • Liver tests: Leflunomide can cause liver tests to rise. These changes are usually mild and improve when the medicine is stopped or reduced. The effects on the liver do not usually cause symptoms unless they are severe so regular blood tests are important. If you develop symptoms such as yellow discolouration of the whites of your eyes or yellow skin, tell your doctor straight away.
  • There have been rare reports of numbness (neuropathy) in patients taking leflunomide.
  • There have been rare reports of lung inflammation in patients taking leflunomide.

What precautions are necessary?

Blood tests

  • As leflunomide may affect liver and blood cells, you must have regular blood tests during your treatment. This is very important as you may not get symptoms with some of these problems.
  • Blood tests are particularly important during the first few months of treatment and when leflunomide is taken with methotrexate.
  • As well as monitoring for side effects, blood tests help to monitor your condition to determine if the treatment is effective.
  • You will need to have full blood counts and liver function tests every 2 to 4 weeks for the first few months of treatment and then every 1 to 3 months after that.
  • Your general practitioner (GP) will be informed about the monitoring schedule. It is important to see your GP if you have been asked to do so as they have an important role to play in monitoring your condition.

Use with other medicines

  • Leflunomide can interact with other medicines. You should tell your doctor (including your general practitioner, rheumatologist and others) about all medicines you are taking or plan to take. This includes over the counter or herbal/naturopathic medicines. You should also mention your treatment when you see other health professionals.
  • In particular, leflunomide can interfere with phenytoin (for epilepsy), warfarin (a blood thinning medicine).
  • If you are taking leflunomide, it is recommended you should not be immunised with ‘live’ vaccines such as MMR (measles, mumps and rubella), BCG (Bacillus Calmette Guerin), OPV (oral polio vaccine), Zostavax (Herpes Zoster) or yellow fever. Talk with your rheumatologist before receiving any vaccines.

Use with alcohol

  • Because leflunomide can affect your liver, you should avoid heavy alcohol use while taking it.
  • It is not known precisely what level of drinking is safe when on leflunomide. However, there is general agreement that 1 to 2 standard drinks taken once or twice a week is unlikely to cause a problem.
  • Drinking more than 4 standard drinks on one occasion, even if infrequently, is strongly discouraged.

Surgery

  • Your surgeon will discuss with you if you should stop leflunomide before or after surgery.

Use in pregnancy and breastfeeding

  • Leflunomide should not be taken during pregnancy or when breastfeeding.
  • If you are a woman of childbearing age you should use effective contraception while taking leflunomide.
  • Because the medicine stays in the body for a long time, you should not conceive for 2 years after stopping treatment. If a couple wishes to conceive, in certain circumstances leflunomide can be ‘washed out’ from the body using other medication.
  • It is not known if it is safe for men wanting to father a child to take leflunomide. Some experts advise leflunomide be ceased and ‘washed out’ in this circumstance.
  • More detailed information is available here.

How to store leflunomide? 

  • Store leflunomide in a cool, dry place, away from direct heat and light (e.g. not in the bathroom).
  • Keep all medicines out of reach of children.

Important things to remember

  • While taking leflunomide you must see your rheumatologist regularly to make sure the treatment is working and to minimise any possible side effects.
  • If you are worried about any possible side effects you should contact your rheumatologist as soon as possible.
  • It is important to have regular blood tests as directed by your doctor.
  • If you are taking leflunomide and plan to become pregnant you must discuss the timing with your doctor.

For more information see the Leflunomide – printable information sheet.

This Information Sheet has been prepared using materials obtained from various sources which have been reviewed by the Australian Rheumatology Association (ARA). It contains general information only and does not contain a complete or definitive statement of all possible uses, actions, precautions, side effects or interactions of the medicines referenced. This information is not intended as medical advice for individual conditions nor for making an individual assessment of the risks and benefits of taking a particular medicine. Decisions regarding the assessment and treatment of patients are the sole responsibility of the treating medical professional, exercising their own clinical judgment and taking into account all of the circumstances and the medical history of the individual patient. ARA has used all reasonable endeavours to ensure the information on which this Information Sheet is based is accurate and up to date. However, the ARA accepts no responsibility or liability for the accuracy, currency, reliability and/or completeness of the information contained in this Information Sheet.  To the maximum extent permitted by law, the ARA expressly disclaims any liability for any injury, loss, harm or damage arising from or in connection with use of and reliance on the information contained in this Information Sheet. This information sheet is copyright and may be reproduced in its entirety but may not be altered without prior written permission from the ARA.Page updated October 2023