Leflunomide (Arava) – Medications for Rheumatoid Arthritis (RA)

Leflunomide (Arava) is the newest of the commonly used DMARDs.  Its effectiveness is similar to Methotrexate and Sulfasalazine, but in practice it is usually used as a second line treatment, if the response to methotrexate hasn’t been good.  It is usually prescribed on its own, but sometimes it is prescribed in conjunction with methotrexate.  This increases the risk of liver damage though, which is the major side effect of concern.

How does Leflunomide work?

From Australian prescriber – “Leflunomide primarily inhibits replication of activated lymphocytes by blocking the de novo synthesis of pyrimidines and hence DNA. It also has a weak anti-inflammatory action.”

What does that mean?  In RA, an increased number of lymphocytes move into the joints and produce substances that cause inflammation and attack the joints, causing pain and swelling.  Leflunomide reduces these lymphocytes, thereby reducing inflammation and damage.

Leflunomide dose

The standard dose is 20 mg/day, however if the patient experiences side effects, it can be started at 10 mg/day.  Sometimes a loading dose is given, 100mg/day for the first three days.  This results in benefits being seen from the drug quicker, but also results in increased side effects, mostly gastrointestinal adverse effects.

Side effects

The most common side effects are nausea and diarrhoea, but this often settles over time.  A very itchy skin rash is less common, as is hair loss.  The most serious side effect is liver toxicity, and therefore alcohol should be avoided while taking leflunomide.  Rarer side effects include bone marrow suppression and infections.

For a complete list of side effects, click here.

Monitoring recommended

Patients need to have their liver function monitored while on leflunomide, usually tested monthly for the first six months.  After that liver function is sometimes checked 2 monthly, but some rheumatologists prefer monthly blood tests.  Blood tests are essential to detect any damage before it is irreversible.

Contraindications

As with methotrexate, leflunomide should not be given to patients with severe immunodeficiency, impaired bone marrow function, or severe uncontrolled infections. As mentioned,  excessive alcohol consumption should be avoided.

Advice in pregnancy/breastfeeding

Leflunomide is not safe in pregnancy or breastfeeding.  Because leflunomide stays in the body for several months, women should not fall pregnant for at least a year after stopping leflunomide.  Men wishing to father a child should discontinue leflunomide and have the drug ‘washed out’ of their system.