Sulfasalazine Mercaptopurine

Azathioprine, chloramphenicol, colchicine, cyclophosphamide, cytarabine, 5-fluorodeoxyuridine, 5-fluorouracil, hydroxyurea, mercaptopurine, metformin, methotrexate, phenobarbital, phenytoin, primidone, proton pump inhibitors, pyrimethamine, sulfasalazine, and vinblastine... 

In addition to being cleared by xanthine oxidase (see sec. III.D), 6-mercaptopurine is cleared by S-methylation catalyzed by the genetically polymorphic thiopurine methyltransferase (134). This enzyme is inhibited by the chug sulfasalazine, leading to bone marrow suppression as a result of increased 6-mercaptopurine concentrations (135,136). 

Mercaptopurine Methotrexate Oral contraceptives p-Ami nosalicylate Phenobarbital Phenyloin Primidone Pyrimethamine Sulfasalazine Tetracycline Vinblastine... 

Thiopurines are metabolized by thiopurine methyltransferase, whose activity is controlled by a common genetic polymorphism in the short arm of chromosome 6. Patients with low or intermediate activity who take azathioprine or 6-mercaptopurine are at risk of myelosup-pression caused by excess accumulation of the active thiopurine metabolite 6-thioguanine nucleotide. Benzoic acid derivatives, such as mesalazine and its precursors, and prodrugs (sulfasalazine, olsalazine, and balsalazide) inhibit thiopurine methyltransferase activity in vitro. This action could explain the increase in whole blood concentrations of 6-thioguanine nucleotide, leading to leukopenia. 

Drug intolerance often limits the usefulness of agents used to treat IBD. Many patients receiving sulfasalazine, mesalamine, corticosteroids, metronidazole, azathioprine, mercaptopurine, or infliximab experience some undesired effects. In some cases, these adverse effects can be significant and require discontinuation of the therapy. Knowledge of the common or important adverse reactions will assist in avoiding or minimizing their effects. 

Traditional medical therapies for Crohn s disease include sulfasalazine and corticosteroids. These are pluripotent, reducing the production of inflammatory mediators and cytokines, although the complex and multiple mechanisms remain incompletely understood. Novel therapies related to newer aminosalicylate preparations such as balsalazide (colazide) or olsalazine (dipentum) newer corticosteroids such as budesonide immunomodulators such as azathioprine, 6-mercaptopurine, or methotrexate and antibiotics such as metronidazole are aimed at more specific delivery of active compounds to the site of disease, reduction of systemic absorption and side effects, and modulation of more focal targets within the immune response and the action of specific proinflammatory cytokines. 

The haematological toxicity of azathioprine and mercaptopurine may be increased by mesalazine, olsalazine or sulfasalazine. Bal-salazide may be less likely to interact but this requires confirmation. 

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