The Rheumatoid Arthritis drug, Arava (leflunomide) produces severe liver reactions, including death, in some patients, according to the European Medicines Evaluation Agency (EMEA).
On March 13, 2001, the EMEA issued a public statement, which reported a total of 296 adverse liver reactions in patients. Of these 129 cases were considered serious, including 2 cases of liver cirrhosis and 15 cases of liver failure, 9 with a fatal outcome. The hepatic reactions occurred within six months of using Arava.
Arava is indicated for the treatment of adult patients with active rheumatoid arthritis as a “disease-modifying antirheumatic drug’ (DMARD). Rheumatoid arthritis is an autoimmune disease affecting the joints.
The statement went on to say that, “in view of the seriousness of these reactions, the EMEA wishes to draw attention to the following”:
* Leflunomide is contraindicated in patients with impairment of liver function.
* Rare cases of severe liver injury, including cases with fatal outcome, have been reported during treatment with leflunomide. Most of the cases occurred within 6 months of initiation of treatment. Although confounding factors were present in many cases, a causal relationship to leflunomide cannot be excluded. It is considered essential that monitoring recommendations are strictly adhered to.
* Concomitant treatment with methotrexate and/or other hepatotoxic medications is associated with increased risk of serious hepatic reactions and is not advisable.
* Prescribers are reminded that Arava should only be prescribed by specialists experienced in the treatment of rheumatoid disease.
The EMEA’s statement does clearly emphasize that 78% of the patients experiencing serious reactions were also taking other medications known to be toxic to the liver. “In addition, in 33 of these serious cases (27%) other risk factors were reported, including a history of alcohol abuse and liver function disturbance.”
Additionally, the EMEA suggests that liver enzyme function should be checked before commencing use of Arava. These checks should continue monthly during the first six months of treatment, and then every eight weeks thereafter.
According to Aventis, the drug’s manufacturer, 200,000 patients have used the drug since it was launched in the US in September 1998 and September 1999.