What is leflunomide?

Leflunomide (brand name Arava) is a disease-modifying antirheumatic drug (DMARD) used to treat rheumatoid arthritis and psoriatic arthritis. It works by blocking an enzyme called dihydroorotate dehydrogenase, which rapidly dividing immune cells need to reproduce. By slowing down these overactive immune cells, leflunomide reduces the inflammation that causes joint pain, swelling, and damage.

Leflunomide is taken as a daily pill and is often used as an alternative to methotrexate, or sometimes alongside it under close monitoring.

How to take it

Usual dose: 20 mg once daily. Some patients start at 10 mg if there are concerns about tolerability.
Can be taken with or without food, at any time of day — just be consistent.
Older prescribing protocols used a loading dose (100 mg daily for 3 days), but this is rarely done anymore because it increases side effects without much added benefit.

Critical warning: Leflunomide causes severe birth defects and must not be taken during pregnancy. It stays in your body for a very long time — up to 2 years after stopping — unless a special washout procedure is performed. See “Things to avoid” below.

What to expect when starting

Leflunomide typically begins working within 4–8 weeks, though full benefit may take a few months.

When first starting, some patients notice:

Diarrhea — this is the most common side effect and usually improves within the first few weeks
Mild nausea
Hair thinning — generally modest, and hair usually recovers over time or with dose reduction

These effects often settle as your body adjusts. Let us know if they persist — a dose reduction to 10 mg often helps.

Lab monitoring

Leflunomide requires regular monitoring to ensure safety:

Liver function tests (LFTs) — leflunomide can elevate liver enzymes
Complete blood count (CBC) — to check blood cell levels
Blood pressure — leflunomide can raise blood pressure in some patients

We check labs monthly when starting and for the first several months, then every 2–3 months once stable. We’ll also monitor your blood pressure at office visits. If you check your blood pressure at home, let us know if readings are consistently elevated.

Side effects to watch for

Persistent diarrhea that doesn’t improve after the first few weeks
Significant hair loss beyond mild thinning
Nausea, loss of appetite, or abdominal pain (could indicate a liver issue)
Yellowing of the skin or eyes
New or worsening high blood pressure
Unusual bruising or bleeding
Numbness or tingling in hands or feet (rare peripheral neuropathy)

Things to avoid

Pregnancy — this is the most important precaution. Leflunomide is highly teratogenic (causes birth defects). Both women and men of reproductive potential must use reliable contraception while taking this medication. Because leflunomide has a very long half-life and stays in the body for up to 2 years after stopping, a cholestyramine washout procedure is required before attempting conception. If you’re thinking about starting a family, talk to us well in advance.
Alcohol — both leflunomide and alcohol are processed by the liver. Minimize or avoid alcohol to reduce the risk of liver toxicity.
Liver disease — leflunomide may not be appropriate if you have pre-existing liver problems.
Live vaccines — avoid live vaccines while on leflunomide. Inactivated vaccines (flu shot, COVID, Shingrix) are safe and recommended.

If you discover you’re pregnant while on leflunomide, contact us immediately. We will start the cholestyramine washout right away.

Leflunomide with methotrexate

Some patients take leflunomide and methotrexate together for more effective disease control. This combination is effective but carries an increased risk of liver toxicity, so we monitor liver labs more frequently (typically monthly) when both are used. This combination is only appropriate with careful oversight.

Frequently asked questions

What is the cholestyramine washout? Cholestyramine is a medication that binds leflunomide’s active metabolite in the gut and speeds its elimination from the body. The standard washout is cholestyramine 8 grams three times daily for 11 days. Without it, leflunomide can remain at detectable levels for roughly 2 years. We use this procedure when stopping leflunomide for pregnancy planning or if we need to rapidly clear it due to side effects.

Will my hair grow back? Hair thinning with leflunomide is usually mild and often improves with dose reduction or after stopping the medication. It rarely causes significant hair loss.

Can I drink any alcohol at all? We generally recommend minimizing alcohol. An occasional drink may be acceptable for some patients, but discuss this with your doctor — especially if your liver enzymes have ever been elevated.

What if I miss a dose? Take it as soon as you remember. If it’s close to your next dose, skip the missed one. Don’t double up. Because leflunomide stays in the body for a long time, missing a single dose won’t cause a flare.

How long will I need to take it? This varies by patient. Many people take leflunomide for years if it’s working well and being tolerated. We’ll revisit your treatment plan regularly to make sure it’s still the best option for you.

This handout is provided for educational purposes and does not replace individualized medical advice. Always follow the specific instructions given by your rheumatologist.

Leflunomide: What You Need to Know