Gastrointestinal side effects are most prevalent such as diarrhea, nausea, and vomiting.

Despite the fact that it is well tolerated by animals, in some cases, side effects such as anorexia, gingivitis, leukopenia, vomiting, pharyngitis, pancreatitis, or abdominal distress do occur. Skin related side effects like erythematous rashes, pruritus, urticaria, and photosensitivity can also happen. Be watchful against the incidents of serious side effects like pericarditis, pericardial effusion or hypotension

Be cautious while administering Methotrexate in animals with confirmed hypersensitivity to the medicine, or in those with conditions like bone marrow suppression, hepatic or renal failures etc. Abstain from administering this medication in pregnant animals. Do not use Methotrexate along with NSAIDs and drugs containing compounds of salicylates, phenylbutazone etc, which could dislodge methotrexate from albumin binding sites, thereby increasing its toxicity. Discuss with the vet the medications the pet is taking as many a medicine such as folic acid or Penicillins could increase the toxicity of Methotrexate, apart from bringing out increased bone marrow suppression and other complications. Conduct regular blood tests to ensure a healthy blood count and if at any point of time, the white blood cell count falls below 4000/mm3 or platelets fall below 100,000/mm3, stop the treatment forthwith and bring the matter to the attention of the veterinarian