What is Leflunomide

Leflunomide, sold under the brand name Arava among others, is an immunosuppressive disease-modifying antirheumatic drug, used in active moderate-to-severe rheumatoid arthritis and psoriatic arthritis. It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Dr. Rajwinder Dhillon

Dr. Rajwinder Dhillon

Niagara Falls, ON
Dr. Saeed Shaikh

Dr. Saeed Shaikh

St Catharines, ON
Dr. John Dickson

Dr. John Dickson

St Catharines, ON

Dr. John Wade, MD, FRCPC, Rheumatologist, talks about the treatment Leflunomide for rheumatoid arthritis and psoriatic arthritis.

Quiz: Do You Understand Leflunomide?

Test your knowledge by answering the following questions:


Leflunomide comes in a 20 milligram or a 40 milligram pill.

Leflunomide comes in a 10 milligram or a 20 milligram pill. Your rheumatologist may start you at a lower dose of around 10 milligrams a day, and if you tolerate it well, he or she may increase your dosage to 20 milligrams a day.

You can develop sores in the nose and mouth as a side effect of taking leflunomide.

Leflunomide is commonly associated with side effects such as diarrhea, hair loss, sores in the nose and mouth, headaches, high blood pressure and cough or shortness of breath.

Getting pregnant while you're taking leflunomide is safe.

Leflunomide is an absolute contraindication for pregnancy or consideration of pregnancy, so your specialist will recommend that you don’t go on leflunomide if you’re of childbearing age. If for some reason you are of childbearing age and you are on leflunomide, it’s very important that you let your specialist know well in advance, because leflunomide stays in your body for months to even years.

Leflunomide is often prescribed for psoriatic arthritis.

Leflunomide is a medication that is commonly used for rheumatoid arthritis and certain types of inflammatory arthritis, such as psoriatic arthritis.

You won't notice the results of leflunomide overnight.

Leflunomide can take several weeks or months to be effective, so you need to be patient.
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Dr. John Wade, MD, FRCPC, Rheumatologist, talks about the treatment Leflunomide for rheumatoid arthritis and psoriatic arthritis.

Dr. John Wade, MD, FRCPC, Rheumatologist, talks about the treatment Leflunomide for rheumatoid arthritis and psoriatic arthritis.

When to Call a Doctor

Patients should call their doctor if they feel sick and want to stop, or they are concerned about any side effects.

Other reasons to call a doctor while taking Arava include:

  • Diarrhea
  • Severe weight loss
  • Shortness of breath
  • Developing a rash
  • Becoming pregnant or planning pregnancy
  • Before having surgery

Dr. John Wade, MD, FRCPC, Rheumatologist, talks about the treatment Leflunomide in women of child bearing age and in pregnancy.

Risk in Pregnancy

Arava can harm an unborn child. Patients who may become sexually active during treatment with this medication are advised to use reliable birth control.

Who Should NOT Take Arava

Patients who should NOT be taking Arava (Leflunomide) include:

  • Patients who have had a previous serious reaction to Arava.
  • Women who are pregnant, planning on becoming pregnant, or currently breast feeding.
  • Men who are planning pregnancy with their partner.
  • Patients with diseases of the liver, kidney, or blood disorders.
  • Patients with active infections.

Patients who are about to have surgery should discuss stopping Arava with their doctor. Patients who become pregnant while taking Arava should notify their doctor immediately.

Taking Arava -Leflunomide

Arava is available as oral tablets in 10 mg, 20 mg, and 100 mg doses.

A dose of 10 mg or 20 mg is usually taken once a day as a single tablet. In some cases, it may be prescribed every other day.

Rheumatologists used to start Arava with three loading doses of 100 mg per day. This is not usually done any more because there is a greater risk of side effects at this dose.

Arava Takes 6 to 8 Weeks to Start Working

It usually takes 6 to 8 weeks for Arava to start working, and it can take up to 6 months to feel the maximum effect.

It is important for patients starting this medicine to keep taking it as prescribed. If the dose is changed, it can take another 6 to 8 weeks to start feeling the effects of the change.

How to Take Arava After Missing a Dose

If a patient forgets to take Arava at their usual time but remembers later on the same day, the missed dose should be taken immediately.

If yesterday’s dose is forgotten, it should be skipped, and the patient should only take their usual dose for the day.

Important Tests and Risks

Regular Blood Tests

Patients taking Arava should have their blood tested every month. It is important to make sure that this medicine isn’t harming the liver or blood counts.

Risk of Combination with Alcohol

Drinking while taking Arava can harm the liver. Patients taking this medicine are advised to stop drinking and avoid alcohol, or at the very least, significantly reduce their consumption of alcohol.

Risk of Infection

Arava can make it a bit harder for people to fight off infections. People taking this medicine should call their doctor they have a fever, think they have an infection, or have been prescribed antibiotics to treat an infection.

Patients taking Arava should coordinate with their doctor to potentially stop treatment around surgery. It can be re-started once things have healed and there’s no sign of infection.


The most common side effect of Arava is nausea and diarrhea.

Monthly blood tests are important to ensure that Arava does not harm the liver or blood counts.

Patients should stop drinking alcohol while taking Arava to reduce the chances of liver side effects.

Arava may cause birth defects and result in miscarriage. Anyone who becomes pregnant while taking this medicine should notify a doctor immediately.

Patients considering pregnancy should consider using a different medication because Arava can stay in the body for up to two years.

MORE COMMON side-effects include:

  • Nausea and diarrhea
  • Skin rash
  • Hair thinning or loss which is reversible when the medication is stopped

RARE side-effects include:

  • Blood Pressure – Arava can rarely cause an increase in blood pressure. Patients starting Arava should tell their doctor if they have high blood pressure.
  • Liver – Arava may irritate the liver. This does not usually cause symptoms but may be found on blood tests. Liver side effects are rare and are usually reversible when caught early through regular monthly blood tests.
  • Bone Marrow – Arava can cause a drop in the numbers of white blood cells (which help fight infection) and platelets (which help to stop bleeding). With monthly blood tests, it is unusual for this to be a serious problem.
  • Infection – Any infections or fevers should be taken seriously and reviewed by a doctor.
  • Tingling in the Hands and Feet – Arava can rarely cause a “pins and needles” feeling, or tingling in the hands and feet.
  • Trouble Breathing – Arava can very rarely cause an allergic reaction in the lungs. Patients should call a doctor if they develop a cough that won’t go away, or develop shortness of breath.

How to minimize the side-effects of Arava:

  • Patients should get regular blood tests as requested by their doctor (usually monthly) to monitor for side effects, and remember to attend their appointments
  • In cases where side effects are a problem, reducing the dose or taking the medicine every other day can often help reduce them. This should only be done with guidance from a doctor.


How Arava – Leflunomide Works

Arava works by suppressing the immune system. It does this by inhibiting an enzyme called dihydroorotate dehydrogenase.

The dihydroorotate dehydrogenase enzyme is associated with a number of functions in the body including the synthesis, or creation, of pyrimidines. This effect makes Arava a member of a class of medications called pyrimidine synthesis inhibitors.

Some of the most important building blocks of DNA and RNA that encode genetic information are derived from pyrimidines: cytosine (C) which is found in both DNA and RNA, thymine (T) which is found in DNA, and uracil (U) which is found in RNA.

The exact mechanisms of how Arava suppresses the immune system is not fully understood.

Many researchers think that Arava suppresses the immune system by depleting the pyrimidine supply used by T-cells, a type of white blood cell in the immune system. It is thought that T-cells need a good supply of pyrimidines to divide and rapidly create more copies of themselves.

Researchers also suspect that other more complex cellular signalling pathways might be involved too.

More research will help to better understand how the immune system becomes suppressed in those who take Arava.

In many types of arthritis, the immune system is not functioning correctly and attacks the body by mistake. By suppressing the immune system, Arava helps stop this attack.

In people with arthritis, this medicine can help reduce pain and swelling (inflammation) in the joints, improve day to day function, and prevent long-term damage caused by joint inflammation.

The suppression of the immune system can also make it a bit harder for the body to fight infections, so people taking Arava should report any fevers or infections to their doctor.

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