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Methotrexate

Prescription
Antimetabolite — antineoplastic / Immunosuppressant
Last reviewed 19 Apr 2026 · PetCare.AI Editorial Team
Species
Dog, Cat
Brands
3 available
Interactions
3 documented
Formulations
2

Mechanism of action

Inhibits dihydrofolate reductase, blocking conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting purine and thymidylate synthesis in rapidly dividing cells

At a glance

Class
Antimetabolite — antineoplastic / Immunosuppressant
Schedule
Prescription
Storage
Store below 25°C, protect from light; handle with gloves (cytotoxic)

Dosing

🐕

Dog

Lymphoma (rescue protocol) / Immune-mediated polyarthritis
Dose
2.5 mg/m²
Route
PO, IV
Frequency
2–3× per week (PO for immunosuppression); high-dose IV per oncology protocol
Max dose
15 mg
Duration: Per protocol; leucovorin rescue with high-dose protocols
🐈

Cat

Lymphoma (rescue protocol)
Dose
2.5 mg/m²
Route
PO, IV
Frequency
2–3× per week
Max dose
5 mg
Duration: Per oncology protocol

Formulations

💊

Tablet — 1

Strength
2.5mg
Available in India
💉

Injection — 1

Strength
25mg/mL
Available in India

Storage

Store below 25°C, protect from light; handle with gloves (cytotoxic)

Safety

Absolute contraindications — do not use

  • Renal insufficiency
    Renally excreted; nephrotoxic at high doses
  • Pre-existing bone marrow suppression

Use with caution

  • Concurrent NSAIDs
    Reduced renal clearance of methotrexate

Adverse effects

Common
GI upset
Myelosuppression
Serious
Severe leukopenia
Hepatotoxicity
Nephrotoxicity
GI ulceration

Monitoring parameters

CBC weeklyBUN/CreatinineHepatic enzymes

Interactions

Contraindicated — 1

Trimethoprim-Sulfamethoxazole
contraindicated
Both are folate antagonists; combined use causes severe bone marrow suppression
Management: Do not combine. If antibiotic needed during methotrexate therapy, use non-folate antagonist.

Major — 2

Meloxicam
major
NSAIDs reduce renal clearance of methotrexate, increasing methotrexate toxicity risk
Management: Avoid NSAIDs during methotrexate therapy. If pain management needed, use opioids.
Metamizole (Dipyrone)
major
Metamizole may reduce renal clearance of methotrexate and both cause bone marrow suppression
Management: Avoid concurrent use during methotrexate therapy. Use opioids for analgesia.

Brands

International

Rheumatrex
Stada

India

Folitrax
IPCA Labs
Biotrexate
Biochem Pharma

FAQs

Frequently asked questions

›What is Methotrexate?
Methotrexate is a antimetabolite — antineoplastic / immunosuppressant used in pets. Inhibits dihydrofolate reductase, blocking conversion of dihydrofolate to tetrahydrofolate, thereby inhibiting purine and thymidylate synthesis in rapidly dividing cells
›What is Methotrexate used for in pets?
Methotrexate is used in veterinary medicine for: Lymphoma (rescue protocol) / Immune-mediated polyarthritis; Lymphoma (rescue protocol).
›What is the Methotrexate dose for dogs?
For dogs, Methotrexate is typically dosed as follows — Lymphoma (rescue protocol) / Immune-mediated polyarthritis: 2.5 mg/m² PO/IV 2–3× per week (PO for immunosuppression); high-dose IV per oncology protocol. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.
›What is the Methotrexate dose for cats?
For cats, Methotrexate is typically dosed as follows — Lymphoma (rescue protocol): 2.5 mg/m² PO/IV 2–3× per week. Always consult your veterinarian for a dose tailored to your pet's weight, age, and condition.
›What are the side effects of Methotrexate?
Common: GI upset, Myelosuppression. Serious (call your vet immediately): Severe leukopenia, Hepatotoxicity, Nephrotoxicity, GI ulceration.
›Does Methotrexate need a prescription?
Yes. Methotrexate is a prescription medication and should only be administered under veterinary supervision.
›When should Methotrexate not be used?
Do not use Methotrexate if: Renal insufficiency; Pre-existing bone marrow suppression.

References

References

Textbooks & handbooks

  • Plumb, D.C. Plumb's Veterinary Drug Handbook. 10th ed., Wiley-Blackwell, 2023.
  • Vail, D.M., Thamm, D.H., & Liptak, J.M. (eds.). Withrow & MacEwen's Small Animal Clinical Oncology. 6th ed., Saunders/Elsevier, 2020.
  • Riviere, J.E., & Papich, M.G. (eds.). Veterinary Pharmacology and Therapeutics. 10th ed., Wiley-Blackwell, 2018.
  • National Research Council. Nutrient Requirements of Dogs and Cats. National Academies Press, Washington DC, 2006.
  • The Merck Veterinary Manual. Merck & Co., Online edition. https://www.merckvetmanual.com/

Clinical guidelines & consensus

  • Fletcher, D.J., Boller, M., Brainard, B.M., et al. "RECOVER Evidence and Knowledge Gap Analysis on Veterinary CPR." Journal of Veterinary Emergency and Critical Care, 2012;22(S1):S102–S131.
  • American Animal Hospital Association. 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. AAHA Press.

Journals & peer-reviewed studies

  • Hogan, D.F., Fox, P.R., Jacob, K., et al. "Secondary prevention of cardiogenic arterial thromboembolism in the cat: The FAT CAT study." Journal of Veterinary Cardiology, 2015;17(Suppl 1):S306–S317.
  • Boswood, A., Häggström, J., Gordon, S.G., et al. "Effect of Pimobendan in Dogs with Preclinical Myxomatous Mitral Valve Disease and Cardiomegaly: The EPIC Study — A Randomized Clinical Trial." Journal of Veterinary Internal Medicine, 2016;30(6):1765–1779.
  • ASPCA Animal Poison Control Center. Toxicology and Poison Management Guidelines. American Society for the Prevention of Cruelty to Animals. https://www.aspca.org/pet-care/animal-poison-control

Regulatory & approvals

  • Central Drugs Standard Control Organisation (CDSCO), Government of India. Veterinary Drug Approval Registry, 1969–2026. Directorate General of Health Services. https://cdsco.gov.in/

Databases

  • Washington State University, College of Veterinary Medicine. Veterinary Clinical Pharmacology Laboratory (VCPL) — MDR1 Multidrug Sensitivity Database. https://vcpl.vetmed.wsu.edu/
Educational reference only
This information is provided for educational purposes and is not a substitute for professional veterinary advice, diagnosis, or treatment. Always consult a qualified veterinarian before administering any medication to your pet. Find a vet near you →

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