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Leflunomide is an anti-rheumatic drug used to treat adult patients with active rheumatoid arthritis or with active psoriatic arthritis.
 BRAND NAMES
- International: Arava
- Australia: Arabloc
- Europe: Arava EPAR summary for the public, Prescribing Information
- Italy: Arava
- U.S.: Arava PI
 MECHANISM OF ACTION
Leflunomide, is an immunosuppressive disease-modifying antirheumatic drug (DMARD). It reduces inflammation by reducing the production of immune cells called lymphocytes, which are responsible for inflammation.
Leflunomide does this by blocking an enzyme called dihydroorotate dehydrogenase (an enzyme involved in de novo pyrimidine synthesis), which is necessary for the lymphocytes to multiply. With fewer lymphocytes, there is less inflammation, helping to control the symptoms of arthritis.
Leflunomide is used to treat adults with active rheumatoid arthritis (an immune system disease causing inflammation of the joints) or active psoriatic arthritis (a disease causing red, scaly patches on the skin and inflammation of the joints).
Leflunomide is not recommended for use in children and adolescents below 18 years of age.
Adults: Treatment usually starts with a loading dose of 100 mg once a day for three days, followed by a maintenance dose. The recommended maintenance dose is 10 to 20 mg once a day in patients with rheumatoid arthritis, and 20 mg once a day in patients with psoriatic arthritis. The medicine usually starts to have an effect after four to six weeks. Its effect may improve further for up to six months.
Hematology parameters and liver enzymes should be monitored: Alanine aminotransferase (ALT) or serum glutamopyruvate transferase (SGPT) and a complete blood cell count, including a differential white blood cell count and a platelet count, must be checked simultaneously and with the same frequency:
- before initiation of leflunomide
- every two weeks during the first six months of treatment, and
- every 8 weeks thereafter
- Known hypersensitivity to leflunomide or to any of the other ingredients.
- Liver disease
- Moderate to severe kidney problems
- Severe immunodeficiency states, such as acquired immune deficiency syndrome (AIDS)
- Poor bone marrow function or low blood cell counts (red cells, white cells or platelets) caused by conditions other than rheumatoid or psoriatic arthritis
- Patients with serious infections
- Women who are or may become pregnant, or during breastfeeding.
 WARNINGS AND PRECAUTIONS
- Hepatotoxicity: Doctors prescribing Leflunomide need to be aware of the risk of liver problems associated with the medicine; Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide. Patients with pre-existing acute or chronic liver disease, or those with serum alanine aminotransferase (ALT) >2×ULN before initiating treatment, should not be treated with Leflunomide. Use caution when Leflunomide is given with other potentially hepatotoxic drugs.
Monitoring of ALT levels is recommended at least monthly for six months after starting treatment, and thereafter every 6-8 weeks. If ALT elevation > 3 fold ULN occurs, interrupt therapy while investigating the probable cause of the ALT elevation by close observation and additional tests. If likely leflunomide-induced, start washout and monitor liver tests weekly until normalized.
Washout procedure: Colestyramine 8 g is administered 3 times daily. Alternatively, 50 g of activated powdered charcoal is administered 4 times daily. Duration of a complete washout is usually 11 days. The duration may be modified depending on clinical or laboratory variables.
- Alcohol: Due to a potential for additive hepatotoxic effects, alcohol consumption should be avoided during treatment with leflunomide.
- Methotrexate: co-administration increases risk of hepatotoxicity. Seventy-five percent of all cases of severe liver damage reported until early 2001 were seen under combined drug therapy leflunomide plus methotrexate
 PREGNANCY AND LACTATION
- Pregnancy: Pregnancy must be excluded before starting treatment. Leflunomide is contraindicated in pregnant women, or women of childbearing potential who are not using reliable contraception. Pregnancy must be avoided during Leflunomide treatment or prior to the completion of the drug elimination procedure after Leflunomide treatment.
 SIDE EFFECTS
The most common side effects (seen in 1-10% of patients) are leucopenia (low white blood cell counts), mild allergic reactions, increased creatine phosphokinase levels (a marker of muscle damage), paraesthesia (abnormal sensations like pins and needles), headache, dizziness, mild increases in blood pressure, diarrhea, nausea, vomiting, inflammation of the mouth such as mouth ulcers, abdominal pain, increased liver enzyme levels, hair loss, eczema, rash, pruritus, dry skin, tenosynovitis (inflammation of the sheath surrounding the tendons), loss of appetite, weight loss and asthenia (weakness).
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