What to Know About Arava (Leflunomide)

Arava (leflunomide) is a once-daily disease-modifying anti-rheumatic drug (DMARD) used to reduce pain, stiffness, and inflammation, and slow disease progression in moderate to severe rheumatoid arthritis (RA) cases. An immune modulator, Arava works to decrease joint damage and prevent disability. It is often prescribed when other DMARDs, such as methotrexate, cannot be tolerated or fail to control RA symptoms. 

Before prescribing Arava, your healthcare provider will weigh the potential benefits against the risks. First approved by the U.S. Food and Drug Administration (FDA) in 1998, the drug now carries black-box warnings from the FDA for potential life-threatening liver disease and fetal harm. 

Uses

Arava is used for moderate to severe cases of RA to tamp down inflammation associated with the disease.

An isoxazole immunomodulatory agent, Arava inhibits dihydroorotate dehydrogenase, an enzyme involved in the excessive immune response that spurs inflammation in RA.

Arava blocks the formation of DNA needed for developing cells, such as those of the immune system. The drug's antiproliferative activity (meaning, its ability to prevent the spread of cells) suppresses the immune system, and, subsequently, halts arthritis progression.

Before Taking

If you've been diagnosed with rheumatoid arthritis, your healthcare provider will likely prescribe methotrexate as a first-line treatment. If you do not have adequate results with methotrexate, your practitioner may prescribe Arava or another DMARD either in addition to or instead of methotrexate.

Prior to taking Arava, your healthcare provider will order blood work to check your baseline liver function, a complete blood count, a tuberculosis test, and a pregnancy test (for women of childbearing age). Your practitioner will also check your blood pressure.

Before starting treatment with Arava, you may need to update your vaccinations, as certain vaccines should be avoided while taking Arava. Vaccines you may need include:

• Pneumonia
• Hepatitis B
• Tetanus booster
• Shingles

Precautions and Contraindications

Due to potentially dangerous side effects, some people may not be good candidates for treatment with Arava. If any of the following apply, Arava is not right for you:

• Severe immunodeficiency
• Bone marrow dysplasia
• Severe or uncontrolled infections
• Pre-existing liver diseases, such as hepatitis or cirrhosis
• A hypersensitivity to leflunomide or any inactive ingredients in Arava tablets
• Pregnancy (or the possibility of pregnancy and no contraception use)
• Breastfeeding

As with all drugs, Arava does pose the risk of certain medication interactions.

Dosage

Arava is available in 10 milligrams (mg) and 20 mg film-coated tablets (30 count bottles). Arava is also available in a 100 mg three-count blister pack.

Arava is typically started in a larger dose, known as a loading dose, of 100 mg for the first three days, then reduced to a daily dose of 20 mg.

Check your prescription and talk to your healthcare provider to make sure you are taking the right dose for you.

It can take several weeks before there is a noticeable improvement in joint pain or joint swelling. Full benefits may not be realized until six to 12 weeks after starting Arava.

Modifications

People who are at an increased risk of liver damage typically skip the loading dose.

If you experience uncomfortable side effects, your healthcare provider may reduce your dose to 10 mg a day.

How to Take and Store

Arava should be taken once daily at or around the same time. If you miss your daily dose, call your practitioner or pharmacist for guidance.

Alcohol should be avoided when taking Arava as it may increase the risk of liver damage. Discuss your alcohol use with your healthcare provider.

Side Effects

The most common side effect of Arava, affecting about 20% of users, is diarrhea. This usually improves with time and can be managed with over-the-counter anti-diarrhea medication. In some cases, the dose of Arava may need to be decreased to address loose stools.

Other common side effects include:

• Nausea
• Headache
• Respiratory infection
• Elevated liver enzymes (ALT and AST)
• Hair loss
• Rash

The elevation of liver enzymes usually affects less than 10% of people taking Arava. But because it can cause liver injury, especially with alcohol use or with certain other drugs, regular blood tests should be performed to monitor the liver.

Likewise, your healthcare provider may want to monitor your blood pressure closely while you are taking Arava, as the drug may cause hypertension.

Serious Side Effects

In rare cases, lung problems, including cough or shortness of breath, can occur in people taking Arava. If you experience any of these side effects, seek immediate medical treatment:

• Rash with or without a fever
• Hives
• Blisters or peeling of skin
• Mouth sores
• Itching
• Difficulty breathing
• New or worsening cough
• Chest pain
• Pale skin

Warnings and Interactions

Arava carries an FDA black-box warning—the strongest warning issued—for embryo-fetal toxicity and hepatoxicity (liver failure).

Severe liver injury, including fatal liver failure, has been reported in some patients who were treated with Arava. Rare reports of pancytopenia, agranulocytosis, and thrombocytopenia have been reported. Blood counts should be performed routinely to watch for abnormalities.

Rare cases of Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptom (DRESS) have been reported in patients treated with Arava. If any of these occur, Arava should be stopped and a drug-elimination procedure may be started.

Peripheral neuropathy has been reported in some patients taking Arava. While in most cases, symptoms subsided with discontinuation of Arava, some patients had persistent symptoms.

Those who are taking teriflunomide or other hepatoxic drugs should not take Arava. Medications that can affect the liver should be used with caution. In addition, the following drugs may interfere with Arava:

• Prevalite (cholestyramine)
• Rifadin or Rimactane (rifampin)