Methotrexate Colestyramine

ANION EXCHANGE RESINS METHOTREXATE Parenteral methotrexate levels may be l by colestyramine Colestyramine interrupts the enterohepatic circulation of methotrexate Avoid co-administration... 

Clinically important, potentially hazardous interactions with amphotericin B, chlorotrianisene, colestyramine, diuretics, estrogens, furosemide, insulin, live vaccines, methotrexate, oral contraceptives, pancuronium, phenobarbital, rifampicin... 

The serum methotrexate levels of three patients given methotrexate by infusion were markedly reduced by colestyramine. 

An 11-year-old girl with osteosarcoma who developed colitis when treated with high-dose intravenous methotrexate, was subsequently given colestyramine 2 g every 6 hours from 6 to 48 hours after the methotrexate. Serum methotrexate levels at 24 hours were approximately halved. A marked fall in serum methotrexate levels was seen in another patient similarly treated. Colestyramine similarly reduced methotrexate levels in cases of toxicity in another two patients. ... 

Methotrexate undergoes enterohepatic recirculation, that is to say it is excreted into the gut in the bile and re-absorbed further along the gut. If colestyramine is given orally, it can bind strongly to the methotrexate in the gut, thereby preventing its reabsorption and, as a result, the serum levels fall. ... 

The documentation seems to be limited. In the cases cited " the colestyramine was deliberately used to reduce serum methotrexate levels. However, in some circumstances it might represent an unwanted interaction. Since methotrexate is excreted into the gut in the bile, separating the oral dosages of the colestyramine and methotrexate may not necessarily prevent their coming into contact and interacting together. Monitor concurrent use. 

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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