Methotrexate (MTX)

What is this medication for?

• Lymphomas (multi-drug protocols, incl. LMP maintenance) and some solid tumors; low-dose rescue for feline lymphocytic cholangitis refractory to prednisolone/chlorambucil

How is it given?

Give exactly as your veterinarian prescribed — never change the dose or stop on your own unless your veterinarian has told you to.

• Never with NSAIDs — the classic community-pharmacy interaction (human RA patients), directly transferable to veterinary analgesic co-prescribing.

What if I miss a dose?

• Give it as soon as you remember — unless it is almost time for the next dose (then skip the missed one; never double up).
• Call your clinic if you miss more than one dose in a row.

Side effects — what should I watch for?

Effects listed as common in this handout

• stomach/intestinal (diarrhea, nausea, vomiting) (Common)

Worth a phone call to your veterinarian

• High-dose: mouth sores/mucosal sloughing, stomach/intestinal ulcers, marrow nadir day 4–6 (Dose-limiting)

⚠️ Contact your veterinarian or an emergency clinic IMMEDIATELY if you notice

• Renal tubular tissue death (precipitation) (High-dose/insufficient hydration)
• Hepatopathy, pulmonary infiltrates/fibrosis, alopecia, depigmentation, rare anaphylaxis (Cumulative/idiosyncratic)

Before starting (or refilling), tell your veterinarian if your pet:

• has or has had: Preexisting marrow depression, severe renal or hepatic insufficiency, hypersensitivity
• has or has had: Accurate dosing essential — small doses, narrow margins; NSAIDs/penicillins reduce renal clearance

• is pregnant, nursing, or used for breeding
• is taking any other medications, supplements, or flea/tick products, including:
  • NSAIDs, salicylates, sulfonamides, penicillins
  • Folic acid supplements
  • Leucovorin
  • Other myelosuppressives
  • Asparaginase

Storage and handling

Reconstituted 10 mg/mL stable 6 weeks refrigerated; human-exposure hazard (teratogen) — pregnant staff must not handle.

Good to know

• The leucovorin-rescue pair is the exam core: MTX blocks DHFR; leucovorin (folinic acid, activated past the block) rescues normal cells — give within the first hour (by 48 h) at 25–200 mg/m² every 6 hours until levels <10⁻⁸ M. Dog lethal dose 10 mg/kg WITHOUT rescue.
• Overdose protocol trio: gut emptying + oral neomycin (blocks enterohepatic reabsorption) + alkaline diuresis (urine pH 7.5–8 with NaHCO₃) to keep MTX soluble and prevent tubular precipitation.
• Never with NSAIDs — the classic community-pharmacy interaction (human RA patients), directly transferable to veterinary analgesic co-prescribing.
• No CSF penetration systemically — CNS disease needs intrathecal dosing or another agent (cytarabine is the CSF-friendlier partner).