Other Immunosuppressants

Mycophenolate mofetil (CellCept) and azathioprine (Imuran) are antimetabolite immunosuppressants used to prevent organ transplant rejection and manage autoimmune conditions. Both target lymphocyte proliferation but through different pathways. Azathioprine is a purine analog converted to 6-mercaptopurine (6-MP), which is inactivated by xanthine oxidase and thiopurine methyltransferase (TPMT). Allopurinol inhibits xanthine oxidase, so concurrent use causes 6-MP to accumulate to dangerous levels — triggering severe pancytopenia. TPMT genetic testing should be done before starting azathioprine; patients with low TPMT activity are at high risk for myelosuppression even at standard doses. Mycophenolate inhibits inosine monophosphate dehydrogenase, selectively blocking de novo purine synthesis in lymphocytes. It is a known teratogen (FDA pregnancy category X equivalent); two forms of contraception are required, and a negative pregnancy test is needed before initiation. Both drugs cause dose-dependent bone marrow suppression, requiring regular CBC monitoring — typically weekly initially, then monthly. GI effects (nausea, diarrhea, abdominal pain) are especially prominent with mycophenolate. Both increase infection risk and long-term malignancy risk, particularly skin cancers and lymphoma.