Leflunomida

Leflunomide

N-(4'-trifluoromethylphenyl)-5-methylisoxazole-4-carboxamide

Agente inmunomoduladorPOPerrosGatos

También conocido como: Arava · HW A 486 · RS 34821 · SU 101

Revisado por el equipo veterinario de VetSheetActualizado 5 abr 2026Referencia veterinaria basada en la evidencia

4-6 mg/kg PO q24h and then to maintain trough plasma levels of 20 micrograms/mLPO· q24h

Peso corporal— 🐕

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
Immunosuppressive as part of a protocol (with cyclosporine) following organ transplant	4-6 mg/kg PO q24h and then to maintain trough plasma levels of 20 micrograms/mL	PO	q24h	—	🌎 NA
Adjunctive immunosuppressive for immune-mediated hemolytic anemia	4 mg/kg PO q24h	PO	q24h	—	🌎 NA
Treatment of systemic and cutaneous reactive histiocytosis	2-4 mg/kg PO once daily to attain trough levels of 20 micrograms/mL	PO	q24h	—	🌎 NA
Treatment of Evans' Syndrome in a diabetic dog	2 mg/kg PO q12h	PO	q12h	Decreased by 25% every 4 weeks for first 4 months, then every 8 weeks	🌎 NA

Treatment of Evans' Syndrome in a diabetic dog: In combination with human intravenous immunoglobulin (hIVIg). Target trough level approx 20 micrograms/mL.

Gatos

Indicación	Dosis	Vía	Frecuencia	Duración	Región
Rheumatoid arthritis	Initially, leflunomide at 10 mg (total dose) PO once daily and methotrexate at 2.5 mg (total dose) PO three times on one day per week. When significant improvement occurs, reduce doses of leflunomide to 10 mg PO twice weekly and methotrexate to 2.5 mg PO once weekly.	PO	q24h initially, then twice weekly	—	🌎 NA

Rheumatoid arthritis: Used in combination with methotrexate.

Las dosis son una referencia clínica para profesionales veterinarios autorizados. Confirme siempre con el prospecto actual y cada paciente individual.

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Resumen

La leflunomida es un fármaco antirreumático modificador de la enfermedad (FAME) utilizado fuera de indicación (off-label) en medicina veterinaria como un potente inmunosupresor ahorrador de esteroides.

Usos clínicos: Se utiliza principalmente en perros para afecciones inmunomediadas refractarias como la anemia hemolítica inmunomediada (AHIM), la poliartritis inmunomediada (PIM), la histiocitosis reactiva sistémica y cutánea, y la meningoencefalitis granulomatosa (MEG). También se utiliza en protocolos de rechazo de trasplantes.
Uso en felinos: Se utiliza ocasionalmente en combinación con metotrexato para la artritis reumatoide felina.
Perla clínica: Debido a que la leflunomida se dirige a la síntesis de novo de pirimidinas (de la cual dependen en gran medida los linfocitos activados), proporciona un efecto inmunosupresor dirigido. Sin embargo, su metabolito activo tiene una vida media excepcionalmente larga, lo que significa que la toxicidad puede persistir mucho después de suspender el fármaco.

Mecanismo de acción

Leflunomide is a prodrug that is rapidly converted in the intestinal mucosa and liver to its active metabolite, teriflunomide (A77 1726 or M1).

Mechanism: Teriflunomide reversibly inhibits the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH).
Pathway: Inhibition of DHODH → prevents the formation of ribonucleotide uridine monophosphate (rUMP) → decreases de novo pyrimidine synthesis → decreases DNA and RNA synthesis.
Result: This induces G1 cell cycle arrest, profoundly inhibiting the proliferation of rapidly dividing autoimmune T-cells and the production of autoantibodies by B-cells.

Seguridad y advertencias

Contraindicaciones

Pregnancy (Category X teratogen)
Hypersensitivity to leflunomide
Pre-existing immunodeficiency
Significant renal impairment
Pregnancy and lactation
Pre-existing severe bone marrow suppression
Severe hepatic impairment
Active severe infections

Efectos adversos

Decreased appetite
Lethargy
Lymphopenia
Alopecia
Rash
Hepatotoxicity
Severe dermatologic reactions (Toxic Epidermal Necrolysis, Stevens-Johnson syndrome - reported in humans)
Gastrointestinal upset (vomiting, diarrhea, anorexia)
Bone marrow suppression (leukopenia, anemia, thrombocytopenia)
Unexplained bleeding

Precauciones

Teratogenicity Warning: Leflunomide is an FDA Category X teratogen. It must not be used in pregnant animals, and pregnant women should not handle this medication.

Prolonged Half-Life: The active metabolite (A77 1726) can persist in the body for up to 2 years after discontinuation. If severe toxicity occurs, a washout procedure using cholestyramine or activated charcoal is required.

Use with extreme caution in patients with hepatic disease, renal impairment, or pre-existing immunodeficiency.

Interacciones farmacológicas

Charcoal, Activated

Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.

Cholestyramine

Can increase elimination and decrease A77 1726 drug concentrations; used for rapid washout.

Hepatotoxic Agents

Increased risk for hepatotoxicity when used concurrently.

Methotrexate

Increased risk of adverse effects and elevated ALT.

Phenytoin

Leflunomide can increase phenytoin levels.

Rifampin

Can increase A77 1726 peak levels.

Vaccines, Live Virus

Should be used with extreme caution, if at all, due to immunosuppression.

Warfarin

Leflunomide may increase INR.

Other immunosuppressants (e.g., cyclosporine, azathioprine)Major

Increased risk of severe immunosuppression and bone marrow toxicity

Live vaccinesMajor

Risk of disseminated infection due to immunosuppression

Monitorización

Complete Blood Count (CBC) for hematologic toxicity (lymphopenia, anemia)
Liver enzymes (ALT, AST, ALP) for hepatotoxicity
Trough levels of A77 1726 (Target is 20 micrograms/mL)
Clinical signs of secondary infections
Gastrointestinal tolerance

Farmacocinética

Vida media

GatosUnknown (Human data: ~15 days for active metabolite)PerrosUnknown (Human data: ~15 days for active metabolite)

Absorción

Rapidly converted to active metabolite A77 1726 (M1) in the GI mucosa and liver. Peak levels occur 6-12 hours post-dose. Food does not affect bioavailability.

Distribución

Highly bound to albumin (>99%).

Metabolismo

Converted to A77 1726 in GI mucosa/liver. Further degraded in the liver as glucuronides and an oxalinic acid compound. Conversion to toxic metabolites is reported to be slower in cats than in dogs.

Eliminación

Excreted in the urine and bile. The active metabolite can be detectable up to 2 years after discontinuation.

Sobredosis

Acute toxicologic studies in mice and rats demonstrate minimally toxic doses of 200 mg/kg and 100 mg/kg, respectively.

Washout Protocol: Because of the extremely long half-life of the active metabolite, cholestyramine or activated charcoal administration is highly recommended to accelerate elimination in cases of overdose or severe toxicity. Contact an animal poison control center for specific washout protocols.

Productos disponibles

Formulaciones

Tablets
10 mg tablet
15 mg tablet
20 mg tablet
100 mg tablet

Etiquetado para humanos

Leflunomide Tablets: 10 mg & 20 mg (Arava®, generic)
Arava 10 mg tablets
Arava 15 mg tablets
Arava 20 mg tablets
Arava 100 mg tablets

Estado regulador

European Union✓ AprobadoMedicamento de prescripciónEMA

POM (Prescription Only Medicine)

United Kingdom✓ AprobadoMedicamento de prescripciónVMD