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One selection filters the source overview, clinical facts, reports and dose calculator. Literature references are not species-filtered.
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Source overview
Recorded excerpts for one species. Each dose remains a separate source entry; no regimen is selected.
Choose one species to view its source overview. All-species evidence remains available below.
View full clinical evidence and sources ↓Clinical evidence
Pending clinical review (PROPOSED)Rule-based (RULE_BASED)— applies to the facts and dose entries in this species selection; individual source records retain their own status.
Indications2
Lymphomas (multi-drug protocols, incl. LMP maintenance) and some solid tumors; low-dose rescue for feline lymphocytic cholangitis refractory to prednisolone/chlorambucil
DogCatExtra-label (EXTRA_LABEL)2 source records · View provenance
- Dog · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Indications table · Not applicable · Extra-label (EXTRA_LABEL) · Pending clinical review (PROPOSED) · Rule-based
Original excerpt: Lymphomas (multi-drug protocols, incl. LMP maintenance) and some solid tumors; low-dose rescue for feline lymphocytic cholangitis refractory to prednisolone/chlorambucil — Extra-label (human drug)
- Cat · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Indications table · Not applicable · Extra-label (EXTRA_LABEL) · Pending clinical review (PROPOSED) · Rule-based
Original excerpt: Lymphomas (multi-drug protocols, incl. LMP maintenance) and some solid tumors; low-dose rescue for feline lymphocytic cholangitis refractory to prednisolone/chlorambucil — Extra-label (human drug)
- Dog · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Indications table · Not applicable · Extra-label (EXTRA_LABEL) · Pending clinical review (PROPOSED) · Rule-based
Dose regimens3
This calculator performs arithmetic only on the sourced dosing field shown for each result — it does not verify the field's accuracy, does not select which field to use for a patient, and does not replace a veterinarian's order. Not for clinical use. Confirm every result against the primary source before dispensing.
Choose one species above to view its dose calculator.
Adverse effects4
GI (diarrhea, nausea, vomiting) — Common
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Side Effects / Adverse Effects table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
High-dose: stomatitis/mucosal sloughing, GI ulcers, marrow nadir day 4–6 — Dose-limiting
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Side Effects / Adverse Effects table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Renal tubular necrosis (precipitation) — High-dose/insufficient hydration
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Side Effects / Adverse Effects table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Hepatopathy, pulmonary infiltrates/fibrosis, alopecia, depigmentation, rare anaphylaxis — Cumulative/idiosyncratic
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Side Effects / Adverse Effects table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Monitoring1
CBC (nadir day 4–6), renal values, serial liver enzymes, pulmonary signs; leucovorin levels-driven rescue if overdose
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Monitoring Parameters · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Contraindications1
Preexisting marrow depression, severe renal or hepatic insufficiency, hypersensitivity
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Contraindications & Warnings table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Precautions5
Accurate dosing essential — small doses, narrow margins; NSAIDs/penicillins reduce renal clearance
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Contraindications & Warnings table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
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 q6h until levels <10⁻⁸ M. Dog lethal dose 10 mg/kg WITHOUT rescue.
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Clinical pearl · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
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.
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Clinical pearl · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Never with NSAIDs — the classic community-pharmacy interaction (human RA patients), directly transferable to veterinary analgesic co-prescribing.
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Clinical pearl · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
No CSF penetration systemically — CNS disease needs intrathecal dosing or another agent (cytarabine is the CSF-friendlier partner).
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Clinical pearl · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Interactions5
NSAIDs, salicylates, sulfonamides, penicillins — ↓ renal clearance / protein displacement → toxicity
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Drug Interactions table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Folic acid supplements — Antagonize effect
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Drug Interactions table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Leucovorin — The rescue antidote (by design)
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Drug Interactions table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Other myelosuppressives — Additive
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Drug Interactions table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Asparaginase — May reduce MTX efficacy (sequencing)
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Drug Interactions table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Pharmacokinetics4
Mechanism — Competitive inhibition of dihydrofolate reductase (DHFR) → blocks THF → no purines/pyrimidines → S-phase kill
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Pharmacokinetics table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Absorption — Oral <30 mg/m² ~60% bioavailability
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Pharmacokinetics table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Distribution — Kidney/spleen/gallbladder/liver/skin; no therapeutic CSF levels unless intrathecal
Other speciesNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Other species · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Pharmacokinetics table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Excretion — Renal — precipitates in tubules at high concentrations (alkaline urine prevents)
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Pharmacokinetics table · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Pregnancy / lactation considerations1
Teratogenic; affects spermatogenesis — avoid.
Species not recordedNot applicable (NOT_APPLICABLE)1 source record · View provenance
- Species not recorded · Plumb's Veterinary Drug Handbook, 7th ed., p. 808–810 — Pregnancy & Lactation · Not applicable · Not applicable (NOT_APPLICABLE) · Pending clinical review (PROPOSED) · Rule-based
Literature references18
References are linked to this drug. Species applicability is not recorded here, so the species filter does not narrow this list. Imported dates do not retain their original precision; confirm dates in the original citation.
- Dexpanthenol Attenuates Methotrexate-Induced Nephrotoxicity Through Modulation of NF-κB-Mediated Inflammation and SIRT1/PGC-1α-NRF2/HO-1-Associated Oxidative Stress Pathways.
Study summary not available in the imported record. Open the original citation to review the study.
- Methotrexate Neurological Toxicities: Current State-of-the-Art.
Study summary not available in the imported record. Open the original citation to review the study.
- Advances in Sarcoidosis.
Study summary not available in the imported record. Open the original citation to review the study.
- Histological effect of methotrexate on submandibular salivary glands in albino rats ( Rattus norvegicus ).
Study summary not available in the imported record. Open the original citation to review the study.
- Renal protective effect of coenzyme Q10 against methotrexate-induced nephrotoxicity in rats.
Study summary not available in the imported record. Open the original citation to review the study.
Sources: PubMed, National Library of Medicine; Plumb DC. Plumb's Veterinary Drug Handbook. 7th ed. PharmaVet Inc; 2011.
Owner information handout
Plain-language medication information to review with the owner. Open the handout to print it or download a PDF.