leflunomide (Arava)

Leflunomide is an oral, disease-modifying drug that is used in the treatment of rheumatoid arthritis. Leflunomide reduces inflammation in the joints that is responsible for both the symptoms of rheumatoid arthritis and the destruction of joints. This reduces symptoms as well as the progressive deformities of the joints caused by the arthritis. Leflunomide reduces inflammation by suppressing the activity of immune cells responsible for the inflammation. Leflunomide suppresses immune cells by inhibiting dihydroorotate dehydrogenase, an enzyme that is necessary for the production of DNA and RNA. Without DNA and RNA the immune cells (and most other types of cells) cannot multiply or function (or exist). Because of its unique and different mechanism of action, leflunomide is of value when added to other medications used for treating rheumatoid arthritis. Leflunomide was approved by the FDA in September 1998.

What brand names are available for leflunomide?

Arava

Is leflunomide available as a generic drug?

No

Do I need a prescription for leflunomide?

Yes

The most frequently reported side effects are:

• diarrhea,
• nausea,
• headache,
• rash,
• itching,
• loss or thinning of hair, and
• weight loss.

Other important side effects of leflunomide include:

• high blood pressure,
• chest pain, and
• abnormal heartbeats.

Since leflunomide suppresses the immune system, it may increase the risk to patients of infections. The most frequently reported infections involve the respiratory tract. Leflunomide may cause fatal liver failure. More often it causes abnormal liver tests in the blood, suggesting damage to the liver. The liver tests usually return to normal with continued treatment. The dose of leflunomide should be reduced if liver tests are persistently greater than twice the upper limit of normal, and leflunomide should be discontinued if the levels remain above three times the upper limit of normal despite a reduction in dose. Leflunomide should not be administered to individuals with liver problems.

The usual dose is 100 mg daily for the first 3 days, followed by 20 mg daily. Doctors may reduce the dose to 10 mg daily if side effects appear. It may require up to four weeks of therapy before improvement of the arthritis are seen. It is not known if ingestion of food or alcohol affects the absorption or action of leflunomide.

Cholestyramine (Questran, Questran Light) and charcoal decrease the concentration of the active form of leflunomide in the blood probably by preventing absorption. Rifampin increases the blood concentration of the active form of leflunomide by 40% probably by increasing the conversion of leflunomide to its active form. This may increase the side effects of leflunomide. Increased activity of warfarin (Coumadin) by leflunomide has been reported rarely. Leflunomide also may increase the blood concentration of tolbutamide.

Leflunomide is harmful to the developing fetus and should not be used during pregnancy.

It is unknown whether leflunomide accumulates in breast milk. Since leflunomide could cause harm to the infant, women taking leflunomide probably should refrain from breastfeeding.

What preparations of leflunomide are available?

10 and 20 mg tablets

How should I keep leflunomide stored?

Leflunomide should be stored at room temperature 15 C - 30 C (59 F - 86 F).