Metotrexato
Methotrexate
Methotrexate sodium
También conocido como: Rheumatrex · Trexall · Methotrexate LPF · MTX · Amethopterin · 4-Amino-4-deoxy-10-methylpteroyl-L-glutamic acid · 4-Amino-10-methylfolic acid · CL-14377 · alpha-methopterin · methotrexatum · metotrexato · NSC-740 · WR-19039
Revisado por el equipo veterinario de VetSheetActualizado 5 abr 2026Referencia veterinaria basada en la evidencia
Esta dosis se basa en la superficie corporal (mg/m²). Convierta el peso en superficie corporal antes de administrarla.
Las dosis son una referencia clínica para profesionales veterinarios autorizados. Confirme siempre con el prospecto actual y cada paciente individual.
Dosis por especie
🌎 NA — North America🌍 EU — Europe
Perros
| Indicación | Dosis | Vía | Frecuencia | Duración | Región |
|---|---|---|---|---|---|
| As part of the LMP protocol for maintenance of canine lymphoma | 2.5-5 mg/m2 PO twice a week | PO | twice a week | — | 🌎 NA |
| In combination with other antineoplastics (per protocol) | 5 mg/m2 PO twice weekly or 0.8 mg/kg IV every 21 days; alternatively 2.5 mg/m2 PO daily | PO/IV | twice weekly, every 21 days, or daily | — | 🌎 NA |
- As part of the LMP protocol for maintenance of canine lymphoma: Given with Chlorambucil 20 mg/m2 PO every 15 days and Prednisone 20 mg/m2 PO every other day. When Vincristine is added it is at a dose of 0.5-0.7 mg/m2 and is given every 15 days alternating weeks with the chlorambucil.
Gatos
| Indicación | Dosis | Vía | Frecuencia | Duración | Región |
|---|---|---|---|---|---|
| For susceptible neoplastic diseases (usually as part of a multi-drug protocol) | 2.5 mg/m2 PO 2-3 times weekly; 0.3-0.8 mg/m2 IV every 7 days | PO/IV | 2-3 times weekly (PO) or every 7 days (IV) | — | 🌎 NA |
| For non-suppurative cholangitis/cholangiohepatitis (CCHC) syndrome with fibrosis | A total dose of 0.4 mg per cat total dose given on one day in three divided doses: 0.26 mg at hour zero, 0.13 mg at the 12 and 24 hour dosing. Repeat every 7-10 days. | PO | Divided over 24 hours, repeated every 7-10 days | — | 🌎 NA |
- For non-suppurative cholangitis/cholangiohepatitis (CCHC) syndrome with fibrosis: Use in conjunction with ursodeoxycholic acid (15 mg/kg PO q24h) and folate (0.25 mg/kg PO q24h).
Las dosis son una referencia clínica para profesionales veterinarios autorizados. Confirme siempre con el prospecto actual y cada paciente individual.
Resumen
El metotrexato (MTX) es un potente antagonista del ácido fólico utilizado en oncología veterinaria principalmente para el tratamiento de trastornos linfoproliferativos (como el linfoma) y ciertos tumores sólidos en perros y gatos.
Más allá de sus propiedades antineoplásicas, posee capacidades inmunosupresoras significativas, lo que lo convierte en una opción valiosa para afecciones inmunomediadas refractarias, como la colangitis/colangiohepatitis felina no supurativa que no ha respondido a la terapia estándar con prednisolona o clorambucilo.
Perla clínica: Debido a que el MTX tiene un índice terapéutico muy estrecho y depende en gran medida de la eliminación renal, la hidratación del paciente y la función renal son primordiales para prevenir una toxicidad grave. Es altamente tóxico para las células que se dividen rápidamente, lo que significa que el epitelio gastrointestinal y la médula ósea son particularmente susceptibles a daños colaterales.
Mecanismo de acción
Methotrexate is an S-phase specific antimetabolite. It acts by competitively and irreversibly inhibiting the enzyme dihydrofolate reductase (DHFR).
- Folic acid → (via DHFR) → Dihydrofolate → (via DHFR) → Tetrahydrofolate (active form).
- By blocking DHFR, MTX prevents the reduction of dihydrofolate to tetrahydrofolate.
- Tetrahydrofolate is an essential cofactor for the synthesis of purines and pyrimidines (specifically thymidylate).
- The depletion of these precursors halts DNA, RNA, and protein synthesis, ultimately leading to apoptosis in rapidly proliferating cells (e.g., neoplasms, bone marrow, GI tract epithelium).
Note: DHFR has a much greater affinity for MTX than for folic acid. Therefore, coadministration of folic acid will not reverse MTX toxicity. Leucovorin calcium (a derivative of tetrahydrofolic acid that bypasses the blocked enzyme) is required as a rescue agent.
Seguridad y advertencias
Contraindicaciones
- Preexisting bone marrow depression
- Severe hepatic insufficiency
- Severe renal insufficiency
- Hypersensitivity to the drug
- Pregnancy (Teratogenic/Embryotoxic - FDA Category X)
- Nursing mothers
- Pre-existing severe bone marrow suppression
- Severe renal impairment
- Severe hepatic impairment
- Pregnancy and lactation (teratogenic and embryotoxic)
- Patients with significant third-space fluid accumulations (e.g., ascites, pleural effusion)
Efectos adversos
- Nausea
- Inappetence (especially in cats)
- GI toxicity (ulcers, mucosal sloughing, stomatitis)
- Hematopoietic toxicity / Myelosuppression (nadir at 4-6 days)
- Hepatopathy
- Renal tubular necrosis
- Depigmentation
- Pulmonary infiltrates and fibrosis
- CNS toxicity (encephalopathy) if given intrathecally
- Anaphylaxis (rare)
- Myelosuppression (neutropenia, thrombocytopenia, anemia)
- Gastrointestinal toxicity (anorexia, vomiting, diarrhea, stomatitis)
- Hepatotoxicity (elevated liver enzymes)
- Nephrotoxicity (especially at high doses due to tubular precipitation)
- Alopecia (rare in most animals, but possible in continuously growing coats)
Precauciones
Use with extreme caution in patients susceptible to or with preexisting clinical signs of MTX adverse reactions. Handling Precautions: Wear gloves or immediately wash hands after handling. Gloves are particularly important if handling split, broken, or crushed tablets. Preparation of intravenous solutions should ideally be performed in a vertical laminar flow hood to avoid human exposure. Teratogenic and may affect spermatogenesis.
Interacciones farmacológicas
Prolonged PO administration (>2 weeks) may inhibit MTX metabolism
Given concomitantly with MTX may decrease MTX efficacy
Potential for increased risk for hepatic toxicity
May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation
May have synergistic action with MTX, but alter the renal elimination of MTX
May increase MTX levels
May reduce MTX efficacy, but folate deficiency increases MTX toxicity
May decrease the absorption of oral methotrexate if given concomitantly
Severe hematologic and GI toxicity risk; use caution in dogs also on MTX
May decrease MTX renal elimination
May inhibit the tubular secretion of MTX and increase its half-life
A similar folic acid antagonist; may increase MTX toxicity and should not be given to patients receiving MTX
Potential for increased risk for hepatic toxicity
Potential for increased risk for hepatic toxicity
May displace MTX from plasma proteins increasing risk for toxicity
May displace MTX from plasma proteins increasing risk for toxicity, but also may reduce MTX absorption and enterohepatic recirculation
MTX may reduce theophylline elimination
Rarely, may increase myelosuppression of MTX
Live virus vaccines should be used with caution, if at all during therapy
Decreased renal clearance of methotrexate, leading to increased serum levels and severe toxicity.
Additive antifolate effects, significantly increasing the risk of severe bone marrow suppression.
May delay the elimination of methotrexate.
Monitorización
- Efficacy of treatment
- Clinical signs of GI irritation and ulceration
- Complete blood counts (with platelets) weekly early in therapy, then every 4-6 weeks (Discontinue if WBC <4000/mm3 or platelets <100,000/mm3)
- Baseline and ongoing renal function tests
- Baseline and ongoing hepatic function tests (liver enzymes)
- Complete Blood Count (CBC) - baseline and prior to each dose (monitor for nadir)
- Renal function panel (BUN, Creatinine, Urinalysis)
- Hepatic enzymes (ALT, AST, ALP, Bilirubin)
- Clinical signs of gastrointestinal toxicity (vomiting, diarrhea, anorexia)
- Hydration status
Farmacocinética
Vida media
Absorción
Well absorbed from the GI tract after oral administration of dosages <30 mg/m2 with a bioavailability of about 60%. Peak levels occur within 4 hours after oral dosing, and between 30 minutes and 2 hours after IM injection.
Distribución
Widely distributed in the body and actively transported across cell membranes. Highest concentrations in kidneys, spleen, gallbladder, liver, and skin. Does not reach therapeutic levels in CSF unless given intrathecally. About 50% bound to plasma proteins and crosses the placenta.
Metabolismo
Minimal hepatic metabolism is noted; primarily excreted unchanged.
Eliminación
Excreted almost entirely by the kidneys via both glomerular filtration and active transport.
Sobredosis
Acute overdosage in dogs is associated with severe exacerbations of adverse effects, particularly myelosuppression and acute renal failure. Acute tubular necrosis occurs secondary to drug precipitation in the renal tubules.
- Toxicity Thresholds: In dogs, the maximally tolerated dose is reported to be 0.12 mg/kg q24h for 5 days. A dose of 10 mg/kg is considered lethal if leucovorin rescue is not performed.
- Decontamination: Empty the gut and prevent absorption using standard protocols if ingestion is recent. Oral neomycin has been suggested to help prevent intestinal absorption.
- Renal Protection: Forced alkaline diuresis should be considered to minimize renal damage. Maintain urine pH between 7.5-8 by adding 0.5-1 mEq/kg of sodium bicarbonate per 500 mL of IV fluid.
- Antidote: Leucovorin calcium is the specific therapy for MTX overdoses. It must be given as soon as possible (preferably within the first hour, definitely within 48 hours). Dogs treated with leucovorin at 15 mg/m2 every 3 hours IV for 8 doses, then IM q6h for 8 doses were able to tolerate very high MTX doses.
Productos disponibles
Formulaciones
- Tablets
- Injection solution
- Powder for injection
- 2.5 mg oral tablet
- 10 mg oral tablet
Etiquetado para humanos
- Methotrexate Sodium Tablets (plain & scored): 2.5 mg, 5 mg, 7.5 mg, 10 mg & 15 mg
- Methotrexate Sodium Injection: 25 mg/mL (as base) in various vial sizes
- Methotrexate Powder for Injection, lyophilized: 1 gram preservative free in single-use vials
- Matrex 2.5 mg tablets
- Methotrexate 2.5 mg tablets
- Methotrexate 10 mg tablets
Estado regulador
Human authorized products often used off-label under the cascade.
Prescription Only Medicine. Handled under cascade regulations.
Sin datos reguladores para: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Almacenamiento y estabilidad
Methotrexate sodium tablets should be stored at room temperature (15-30°C) in well-closed containers and protected from light. The injection and powder for injection should be stored at room temperature (15-30°C) and protected from light.
Información para el cliente
ADVERTENCIA: AGENTE DE QUIMIOTERAPIA Este medicamento es altamente tóxico y puede ser peligroso para los humanos si se manipula de forma inadecuada.
- Seguridad en la manipulación: Use siempre guantes desechables al administrar las tabletas, especialmente si están trituradas o divididas. Si no se utilizan guantes, lávese bien las manos inmediatamente después de manipular el medicamento. Las mujeres embarazadas o las personas inmunocomprometidas deben evitar manipular este fármaco.
- Riesgos de toxicidad: Debe ser consciente de las posibilidades de que se desarrolle una toxicidad grave por este medicamento, incluida la mortalidad relacionada con el fármaco.
- Cuándo llamar al veterinario: Comuníquese con su veterinario inmediatamente si su mascota presenta signos clínicos de depresión profunda, letargo, sangrado anormal (incluyendo diarrea con sangre, heces negras y alquitranadas), hematomas, vómitos o pérdida de apetito.
- Lactancia: No permita que las mascotas que reciben este medicamento amamanten a sus crías; cambie a un sustituto de leche.
La referencia de medicamentos de VetSheet está destinada a profesionales veterinarios autorizados como ayuda para la toma de decisiones clínicas, no como sustituto del criterio profesional ni del prospecto actual del fabricante.