Leflunomide (Arava)
Arava (Leflunomide) is a Disease Modifying Anti-Rheumatic Drug (DMARD) that suppresses the immune system to treat rheumatoid arthritis, psoriatic arthritis, and other types of arthritis.
Leflunomide belongs to a class of medications known as pyrimidine synthesis inhibitors.
Taking Leflunomide
Leflunomide 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 Leflunomide 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.
It usually takes 6 to 8 weeks for Leflunomide 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.
If a patient forgets to take Leflunomide 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
Patients taking Leflunomide should have their blood tested every month. It is important to make sure that this medicine isn’t harming the liver or blood counts.
Drinking while taking Leflunomide 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.
Leflunomide 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 Leflunomide 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.
Leflunomide can harm an unborn child. Patients who may become sexually active during treatment with this medication are advised to use reliable birth control.
Science
Leflunomide 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 Leflunomide 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 Leflunomide suppresses the immune system is not fully understood.
Many researchers think that Leflunomide 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 Leflunomide.
In many types of arthritis, the immune system is not functioning correctly and attacks the body by mistake. By suppressing the immune system, Leflunomide 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 Leflunomide should report any fevers or infections to their doctor.
Safety
The most common side effect of Leflunomide is nausea and diarrhea.
Monthly blood tests are important to ensure that Leflunomide does not harm the liver or blood counts.
Patients should stop drinking alcohol while taking Leflunomide to reduce the chances of liver side effects.
Leflunomide 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 Leflunomide 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 – Leflunomide can rarely cause an increase in blood pressure. Patients starting Leflunomide should tell their doctor if they have high blood pressure.
- Liver – Leflunomide 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 – Leflunomide 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 – Leflunomide can rarely cause a “pins and needles” feeling, or tingling in the hands and feet.
- Trouble Breathing – Leflunomide 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 Leflunomide:
- 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.
Patients who should NOT be taking Leflunomide include:
- Patients who have had a previous serious reaction to Leflunomide.
- 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 Leflunomide with their doctor. Patients who become pregnant while taking Leflunomide should notify their doctor immediately.
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 Leflunomide include:
- Diarrhea
- Severe weight loss
- Shortness of breath
- Developing a rash
- Becoming pregnant or planning pregnancy
- Before having surgery
Video
Watch rheumatologist Dr. Andy Thompson introduce Leflunomide in a short 3-minute video: