What You Should Know About Arava

Often Prescribed If Methotrexate Is Unsatisfactory

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Arava (leflunomide) is classified as a disease-modifying anti-rheumatic drug (DMARD). The drug, which was approved by the U.S. FDA on September 11, 1998, is used to treat moderate to severely active rheumatoid arthritis in adults. It is used to reduce the signs and symptoms of rheumatoid arthritis, to inhibit structural damage (e.g., x-ray evidence of erosions and joint space narrowing), and to improve physical function. Arava is often prescribed when other DMARDs, especially methotrexate, cannot be tolerated or produce an inadequate response (i.e., fail to control symptoms).

Availability and Dosing

Arava is available in 10 mg and 20 mg film-coated tablets (30 count bottles). Arava is also available in a 100 mg 3-count blister pack. Because of the long half-life of Arava in rheumatoid arthritis patients and the recommended interval of 24 hours for dosing, it is recommended that Arava be started with a loading dose of one 100 mg tablet per day for 3 days. After the loading dose is complete, a daily dose of 20 mg Arava is recommended for the treatment of rheumatoid arthritis. The 10 mg tablet is available for patients requiring a lower dose because of side effects experienced with the higher dose. It can take several weeks before there is noticeable improvement in joint pain or joint swelling. Full benefits may not be realized until 6 to 12 weeks after Arava was started.

How It Works

Arava is an isoxazole immunomodulatory agent which inhibits dihydroorotate dehydrogenase, an enzyme involved in pyrimidine synthesis. Pyrimidines are building blocks of nucleic acid. Arava is associated with antiproliferative activity (meaning, it prevents the spread of cells) and in trials, it has shown anti-inflammatory effects. It blocks the formation of DNA which is needed for developing cells, such as immune system cells. By doing so, it suppresses the immune system. How it specifically works to control rheumatoid arthritis is not fully understood.

Side Effects and Adverse Reactions

The most common adverse reactions associated with Arava include diarrhea, nausea, headache, respiratory infection, elevated liver enzymes (ALT and AST), alopecia, and rash. The elevation of liver enzymes usually affects less than 10% of patients 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.

An array of adverse events were reported to affect 1% to less than 3% of rheumatoid arthritis patients who participated in clinical trials for Arava. Lung problems, including cough or shortness of breath, are considered rare side effects. Patients should be made aware of the early symptoms of interstitial lung disease and report those symptoms if experienced.

Diarrhea, the most common side effect, affects about 20% of patients treated with Arava. Diarrhea due to Arava use usually improves with time or by taking a medication to prevent diarrhea. In some cases, the dose of Arava may need to be decreased.

Warnings and Contraindications

Arava should not be used by pregnant women or by women who can become pregnant and are not using contraception. Pregnancy must be avoided during treatment with Arava as well as prior to completion of the drug elimination procedure after treatment with Arava.

Severe liver injury, including fatal liver failure, has been reported in some patients who were treated with Arava. Patients with pre-existing acute or chronic liver disease should not be treated with Arava.

Arava is not recommended for patients with severe immunodeficiency, bone marrow dysplasia, or severe or uncontrolled infections. Rare reports of pancytopenia, agranulocytosis, and thrombocytoplenia have been reported. Blood counts should be performed routinely to watch for abnormalities.

Rare cases of Stevens-Johnson syndrome and toxic epidermal necrolysis, and DRESS (drug reaction with eosinophilia and systemic symptoms) have been reported in patients treated with Arava. If this occurs, Arava should be stopped and the 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.

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  1. Arava Tablets. Prescribing Information. Sanofi-Aventis U.S. Revised November 2014.

  2. Leflunomide (Arava). American College of Rheumatology. Updated May 2015.