Leflunomide Charcoal, activated

Leflunomide selectively inhibits pyrimidine synthesis and prevents T-cell proliferation, which is thought to be important in the pathogenesis of rheumatoid arthritis. The onset of action is faster than other DMARDs, providing clinical benefit in 4-6 weeks. As the drug is retained in the body for 2 years, elimination therapy with either cholestyramine or activated charcoal may be necessary if a change to another DMARD is planned. 

Usually, overdosage and adverse events can be managed by dosage reduction, the addition of colestyramine, and symptomatic therapy (36). However, in one study in patients with rheumatoid arthritis, leflunomide 10 mg/ day compared with 20 mg/day was associated with less efficacy and more adverse events leading to treatment withdrawal (24). Colestyramine 3x8 g/day for 11 days is recommended to wash out leflunomide, if A77 1726 plasma concentrations do not fall to 0.02 mg/1 or less, additional colestyramine is advised. Without this washout procedure, it can take up to 2 years to reach A77 1726 plasma concentrations of 0.02 mg/1. Oral activated charcoal 50 g every 6 hours for 24 hours also reduced plasma A77 1726 concentrations (80). 

The serum levels of the active metabolite of leflunomide are reduced by activated charcoal, and colestyramine. The manufacturers advise against the concurrent use of alcohol because of the potential for hepatotoxicity. Methotrexate may also increase leflunomide hepatotoxicity, so in general the combination is not recommended. A case of fatal fulminant hepatic failure has been reported in a patient taking leflunomide and itraconazole. A case of peripheral neuropathy has been reported in a patient taking leflunomide and tegafiir/uraciL The manufacturers predict interactions between leflunomide and phenytoin or tolbutamide, and advise caution with rifampicin as it may increase leflunomide metabolite levels. No clinically relevant interaction occurs with cime-tidine, corticosteroids or NSAIDs. 

The manufacturers say that the concurrent use of leflunomide and other DMARDs (they list azathioprine, chloroquine, hydroxychloroquine, intramuscular or oral gold and penicillamine) has not yet been studied but they say that combined use is not advisable because of the increased risk of serious adverse reactions (haemo- or hepatotoxicity). As the active metabolite of leflunomide has a long half life of 1 to 4 weeks the manufacturers say that a washout of colestyramine or activated charcoal should be given if patients are to be started on other DMARDs. See also Methotrexate, below. 

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