Methotrexate

Methotrexate In Dogs & Cats: Uses, Dosage and Side Effects

Overview

• This compound is an antimetabolite antineoplastic agent that specifically targets the S-phase of the cell cycle.
• It competitively inhibits the enzyme folic acid reductase, which plays a crucial role in purine synthesis, DNA synthesis, and cellular replication.
• Consequently, this leads to the suppression of DNA synthesis and functionality.

Uses of Methotrexate

• Treatment of lymphoma, although its use in animals is often limited by toxicity.
• Also reports of use in canine atopic dermatitis.

Dose of Methotrexate in Dogs and Cats

Dogs:

• All uses: 2.5–5 mg/m2 p.o. twice weekly.
• Adjust the frequency of dosing according to toxic effects.

Cats:

• All uses: 2.5 mg/m2 p.o. twice weekly.
• Adjust the frequency of dosing according to toxic effects.

Side Effects of Methotrexate in Dogs and Cats

• The administration of high dosages of this substance has been associated with several adverse effects, including gastrointestinal ulcers, mucositis, hepatotoxicity, nephrotoxicity, alopecia, depigmentation, pulmonary infiltrates, and haemopoietic toxicity.
• Hypotension and cutaneous manifestations are observed in the human population.
• Anaphylaxis is an infrequent occurrence.

Contraindications of Methotrexate in Dogs and Cats

• Pre-existing myelosuppression, severe hepatic or renal insufficiency, or hypersensitivity to the drug.

Some Notes:

• Methotrexate exhibits a strong affinity for serum albumin, leading to its high degree of binding.
• Consequently, the presence of phenylbutazone, phenytoin, salicylates, sulphonamides, and tetracycline may displace methotrexate from its binding sites.
• This displacement might result in elevated levels of methotrexate in the bloodstream, potentially leading to higher toxicity.
• The administration of folic acid supplements has been found to potentially impede the efficacy of methotrexate treatment, although it should be noted that a lack in folate can actually exacerbate the toxicity associated with methotrexate.
• The use of methotrexate has been shown to enhance the cytotoxic effects of cytarabine. The cellular absorption is observed to be reduced by hydrocortisone, methylprednisolone, and penicillins, while it is enhanced by vincristine.
• The simultaneous utilisation of nonsteroidal anti-inflammatory drugs (NSAIDs) has been found to elevate the likelihood of experiencing adverse effects related to blood, kidney, and liver toxicity.