From Dog

Methotrexate is an antimetabolite chemotherapy drug.

This drug competitively inhibits dihydrofolic acid reductase, which is normally reduced to tetrahydrofolates in purine nucleotide and thymidine synthesis. Thus, methotrexate interferes with DNA synthesis, repair, and cellular replication.

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] characterized by leucopenia, and in some dogs, a protein-losing enteropathy may ensue, requiring special attention[3].

High-doses of folic acid or calcium folinate (leucovorin)[4] are usually administered to accelerate methotrexate elimination to avoid acute renal injury[5].

Recommended dose is 2.5 mg/m2 orally once daily or 5.0 mg/m2 orally on days 1 and 5 of a biweekly maintenance schedule.


  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. Lewis DH et al (2010) Use of calcium folinate in the management of accidental methotrexate ingestion in two dogs. J Am Vet Med Assoc 237(12):1450-1454
  5. Takeuchi A et al (2001) Role of kidney-specific organic anion transporters in the urinary excretion of methotrexate. Kidney Int 60(3):1058-1068