Is Methotrexate safe for dogs and cats?
High risk for petsMethotrexate is used in veterinary oncology for treatment of certain lymphomas, mast cell tumors, and other neoplasias in dogs, typically as part of multi-agent chemotherapy protocols (e.g., CHOP-based lymphoma protocols). Therapeutic use requires veterinary oncologist supervision and careful dose monitoring. Dogs are susceptible to the same toxicity spectrum as humans: myelosuppression (neutropenia is the primary dose-limiting toxicity — CBC monitoring required), GI toxicity (mucositis, diarrhea), and hepatotoxicity. Dogs do not undergo leucovorin rescue as routinely as human patients but supportive care (fluid therapy, antibiotics for febrile neutropenia, antiemetics) is standard. Accidental ingestion of methotrexate tablets (from human prescriptions) by dogs is a veterinary emergency — even a single tablet (2.5 mg human tablet in a small dog at 0.1–0.5 mg/kg) can produce significant myelosuppression and GI toxicity. Leucovorin rescue should be initiated promptly following accidental exposure.
What is methotrexate?
The IUPAC name is (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid.
Also known as: (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid, Rheumatrex, Amethopterin, Metatrexan.
- IUPAC name
- (2S)-2-[[4-[(2,4-diaminopteridin-6-yl)methyl-methylamino]benzoyl]amino]pentanedioic acid
- CAS number
- 59-05-2
- Molecular formula
- C20H22N8O5
- Molecular weight
- 454.4 g/mol
- SMILES
- CN(CC1=CN=C2C(=N1)C(=NC(=N2)N)N)C3=CC=C(C=C3)C(=O)NC(CCC(=O)O)C(=O)O
- PubChem CID
- 126941
Risk for dogs
High riskMethotrexate is used in veterinary oncology for treatment of certain lymphomas, mast cell tumors, and other neoplasias in dogs, typically as part of multi-agent chemotherapy protocols (e.g., CHOP-based lymphoma protocols). Therapeutic use requires veterinary oncologist supervision and careful dose monitoring. Dogs are susceptible to the same toxicity spectrum as humans: myelosuppression (neutropenia is the primary dose-limiting toxicity — CBC monitoring required), GI toxicity (mucositis, diarrhea), and hepatotoxicity. Dogs do not undergo leucovorin rescue as routinely as human patients but supportive care (fluid therapy, antibiotics for febrile neutropenia, antiemetics) is standard. Accidental ingestion of methotrexate tablets (from human prescriptions) by dogs is a veterinary emergency — even a single tablet (2.5 mg human tablet in a small dog at 0.1–0.5 mg/kg) can produce significant myelosuppression and GI toxicity. Leucovorin rescue should be initiated promptly following accidental exposure.
Risk for cats
High riskCats are used rarely in veterinary oncology with methotrexate due to greater sensitivity to its toxicity profile. Methotrexate has been used in some feline lymphoma protocols but is generally less favored than chlorambucil or other agents due to pronounced GI toxicity and myelosuppression in this species. Accidental ingestion by cats — of human oral methotrexate tablets — is a veterinary emergency. Clinical signs of acute methotrexate toxicity in cats include severe myelosuppression (pancytopenia within 3–7 days), bloody diarrhea, vomiting, oral ulceration, and prostration. Leucovorin administration should begin as soon as possible following known ingestion to competitively rescue normal tissues from DHFR inhibition.
Regulatory consensus
4 regulatory and scientific bodies have classified Methotrexate. The classifications differ — that's the data.
| Agency | Year | Classification | Notes |
|---|---|---|---|
| IARC | 2012 | Group 1 | IARC Group 1 classification for methotrexate based on sufficient evidence of carcinogenicity in humans — specifically, immunosuppression-related lymphomas (including non-Hodgkin lymphoma) associated with long-term immunosuppressive therapy. Methotrexate at low doses used in autoimmune disease (rheumatoid arthritis, psoriasis) is associated with increased lymphoma risk primarily through immunosuppression-mediated mechanisms; some lymphomas regress on drug withdrawal. At higher doses used in oncology, the carcinogenic risk must be weighed against the therapeutic benefit for life-threatening malignancies. |
| EPA CTX / IARC | — | Group 3 - Not classifiable as to its carcinogenicity to humans | |
| EPA CTX / Genetox | — | Genotoxicity: positive (Ames: positive, 16 positive / 3 negative reports) | |
| EPA CTX / Genetox | — | Genotoxicity: positive (Ames: positive, 16 positive / 3 negative reports) |
Regulators apply different standards of evidence — animal-data weighting, exposure-pattern assumptions, epidemiological power thresholds — which is why two scientific bodies can review the same data and reach different conclusions. The disagreement is the data.
Where pets encounter methotrexate
- Industrial Facilities — Manufacturing plants, Chemical storage areas, Waste treatment sites
- Occupational Environments — Factories, Warehouses, Transportation vehicles
Safer alternatives
Lower-risk approaches that achieve a similar outcome to Methotrexate:
-
Alternative drug class; Non-pharmacological therapy; Lowest effective dose
Trade-offs: Direct chemical substitution requires verification that the replacement does not introduce new hazards (regrettable substitution). Conduct full hazard assessment of proposed alternative before adoption.Relative cost: 1.2-2×
Frequently asked questions
Is methotrexate safe for pets?
Methotrexate is used in veterinary oncology for treatment of certain lymphomas, mast cell tumors, and other neoplasias in dogs, typically as part of multi-agent chemotherapy protocols (e.g., CHOP-based lymphoma protocols). Therapeutic use requires veterinary oncologist supervision and careful dose monitoring. Dogs are susceptible to the same toxicity spectrum as humans: myelosuppression (neutropenia is the primary dose-limiting toxicity — CBC monitoring required), GI toxicity (mucositis, diarrhea), and hepatotoxicity. Dogs do not undergo leucovorin rescue as routinely as human patients but supportive care (fluid therapy, antibiotics for febrile neutropenia, antiemetics) is standard. Accidental ingestion of methotrexate tablets (from human prescriptions) by dogs is a veterinary emergency — even a single tablet (2.5 mg human tablet in a small dog at 0.1–0.5 mg/kg) can produce significant myelosuppression and GI toxicity. Leucovorin rescue should be initiated promptly following accidental exposure.
What products contain methotrexate?
Methotrexate appears in: Manufacturing plants (Industrial facilities); Chemical storage areas (Industrial facilities); Factories (Occupational environments); Warehouses (Occupational environments).
Why do regulators disagree about methotrexate?
Methotrexate has been classified by 4 agencies including IARC, EPA CTX / IARC, EPA CTX / Genetox, EPA CTX / Genetox, with differing conclusions. Regulators apply different standards of evidence (animal data weighting, exposure-pattern assumptions, epidemiological power thresholds), which is why two scientific bodies can review the same data and reach different conclusions. See the regulatory consensus table on this page for the full picture.
See Methotrexate in the pets app
Look up products containing methotrexate, compare to alternatives, and explore the full data record.
Open in pets View raw API dataSources (5)
- IARC Monographs Volume 100A: Pharmaceuticals — Methotrexate, Group 1 Classification (Immunosuppression-Associated Lymphomas) (2012) — regulatory
- US FDA: Methotrexate Prescribing Information — Indications, Dosing, Black Box Warnings (Myelosuppression, Hepatotoxicity, Pulmonary Toxicity, Teratogenicity), and Leucovorin Rescue (2022) — regulatory
- ASPCA Animal Poison Control Center: Methotrexate Toxicosis in Dogs and Cats — Emergency Management and Leucovorin Rescue Protocol (2023) — veterinary
- Plumb's Veterinary Drug Handbook (10th ed.) — Methotrexate: Veterinary Oncology Use and Toxicity Management (2023) — veterinary
- NIOSH: Safe Handling of Hazardous Drugs — Antineoplastic Agents, PPE Requirements, Engineering Controls, and Pharmaceutical Waste Disposal (2016) — regulatory
Reference data, not professional advice. Aggregates publicly available regulatory and scientific data; not a substitute for veterinary, medical, legal, or regulatory advice. Why we built ALETHEIA →