Arava (Leflunomide) for Psoriasis and Psoriatic Arthritis

Arava (leflunomide) is an oral drug that can be used to treat psoriatic arthritis and moderate to severe psoriasis. Approved for use by the U.S. Food and Drug Administration (FDA) in 1998, Arava is classified as a disease-modifying anti-rheumatic drug (DMARD) which works by tempering the immune response. While clinical studies have shown that Arava is just as effective as methotrexate in treating autoimmune disorders like, it is not as commonly used due in large part to the risk of side effects.

In addition to the original brand name drug, Arava is widely available in generic form under its chemical name leflunomide.

Arava is one of the older DMARDs used to treat psoriatic arthritis and moderate to severe psoriasis. This places it in a group of drugs, like methotrexate and Sandimmune (cyclosporine), that treat autoimmune diseases by suppressing the immune response as a whole. Newer biologic drugs like Humira (adalimumab) and Cimzia (certolizumab pegol) only suppress specific portions of the immune system and, as a result, tend to be more effective with fewer systemic side effects.

For its part, Arava works by blocking the synthesis of pyrimidine, an organic compound that immune cells, namely T-cells, need to function. By removing the "fuel" that T-cells need to survive, the overall immune response is reduced as well as the chronic inflammation inherent to autoimmune diseases.

The FDA originally approved for the treatment of rheumatoid arthritis (a.k.a. autoimmune arthritis). Technically speaking, Arava has never been approved by the FDA to treat either psoriasis or psoriatic arthritis. However, because they share similar disease pathways to rheumatoid arthritis, Arava is often prescribed "off label" to when methotrexate and other drugs fail to provide relief. It is almost never used in first-line therapy or for people with mild to moderate psoriasis.

Arava is approved for use in adults only. The safety and effectiveness of Arava have not been established in children, who will likely have better and safer treatment options than Arava.

Arava is available as an oral pill in 10-milligram (mg), 20-mg, and 100-mg doses. It is taken by the mouth with food and generally prescribed as follows:

• Start by taking 100 mg for three days as a "loading dose."
• Thereafter, take 20 mg daily as a "maintenance dose."

If the 20-mg dose is not well tolerated, it can be reduced to 10 mg daily.

Side effects are common with Arava, some of which may persistent or intolerable. Those affecting at least 1 percent of users include (by order of frequency):

• Diarrhea
• Respiratory tract infections
• Hair loss
• High blood pressure
• Rash
• Nausea
• Bronchitis
• Headache
• Abdominal pain
• Back pain
• Indigestion
• Urinary tract infection
• Dizziness
• Other infections
• Joint pain and inflammation
• Itchiness
• Weight loss
• Loss of appetite
• Cough
• Gastroenteritis ("stomach flu")
• Sore throat
• Mouth sore
• Vomiting
• Weakness
• Allergic reaction
• Chest pain
• Eczema
• Paresthesia (abnormal skin sensations)
• Pneumonitis (lung inflammation)
• Runny nose
• Gallstones
• Shortness of breath

Other immunosuppressive drugs should not be used with Arava as the cumulative effect may cause severe and even life-threatening infections or complications. The concurrent use of methotrexate, in particular, may lead to severe or even fatal liver damage.

Similarly, live attenuated vaccines (those made living but disabled viruses) should not be used while taking Arava as they can cause the very illness they were trying to prevent due to the lack of an immune response. If you need vaccination for any reason, either get vaccinated before Arava is started or ask your doctor if an inactivated (dead) vaccine is available.

Arava can also interact with drugs that use an enzyme called cytochrome (CYP) for metabolization. Arava also relies on CYP and may end up competing for the enzyme if taken together with these drugs. In some cases, this may cause a drug concentration to rise (increasing the risk toxicity and side effects) or drop (reducing the drug efficacy).

The drugs most prone to interaction with Arava include:

• Cephalosporin antibiotics like Ceclor (cefaclor)
• H2 blockers like Tagamet (cimetidine) and Zantac (ranitidine)
• Prandin (repaglinide), used to treat diabetes
• Rifampin used to treat tuberculosis
• Statin drugs like Crestor (rosuvastatin) and Lipitor (atorvastatin)
• St. John's Wort

The FDA has issued two black box warnings about Arava. The warnings highlight potentially devastating risks in two specific populations in whom Arava is contraindicated:

• Pregnant women need to avoid Arava due to the high risk of birth defects, including severe organ malformations, hydrocephalus, and miscarriage. Arava is classified as a Pregnancy X drug, indicating that it should never be used during pregnancy. Breastfeeding should also be avoided.
• People with pre-existing liver disease (including those with cirrhosis or chronic hepatitis C or whose ALT liver enzymes are below 2) need to avoid Arava as well. Severe liver injuries, including fatal liver failure, have occurred as a result of Arava use.

To reduce the risk, women of reproductive age should undergo pregnancy testing prior to starting Arava and use contraception during treatment and up to two years after treatment until all traces of the drug metabolite (teriflunomide) has been eliminated from the body.

To prevent liver injury, a screening for liver disease or dysfunction should be performed prior to the start of treatment. Even in people with no indication of liver problems, liver enzymes should be routinely monitored every month for the first six months of treatment and every six to eight weeks thereafter.

Arava should also be avoided in anyone with a known hypersensitivity to leflunomide or any of the other ingredients in the drug. This also includes people allergic to the drug Aubagio (teriflunomide) used to treat multiple sclerosis.