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Methotrexate is an antimetabolite chemotherapy drug.

This drug is rarely used alone and is used in treatment of lymphoma in combination with L-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone[1].

The main side-effects of this drug are vomiting, diarrhea and bone marrow suppression[2], and in some dogs, a protein-losing enteropathy may ensue, requiring special attention[3].

High-doses of folic acid are usually administered to accelerate methotrexate elimination to avoid acute renal injury[4].


  1. Simon D et al (2008) Efficacy of a continuous, multiagent chemotherapeutic protocol versus a short-term single-agent protocol in dogs with lymphoma. J Am Vet Med Assoc 232(6):879-885
  2. Yu C et al (2000) Cytotoxic T lymphocyte antigen 4-immunoglobulin fusion protein combined with methotrexate/cyclosporine as graft-versus-host disease prevention in a canine dog leukocyte antigen-nonidentical marrow transplant model. Transplantation 69(3):450-454
  3. Yuki M et al (2006) A case of protein-losing enteropathy treated with methotrexate in a dog. J Vet Med Sci 68(4):397-399
  4. Takeuchi A et al (2001) Role of kidney-specific organic anion transporters in the urinary excretion of methotrexate. Kidney Int 60(3):1058-1068