Mitotano
Mitotane
o,p'-DDD (1-chloro-2-[2,2-dichloro-1-(4-chlorophenyl)ethyl]benzene)
También conocido como: Lysodren · o,p'-DDD · CB-313 · NSC-38721 · WR13045 · Lisodren
Revisado por el equipo veterinario de VetSheetActualizado 5 abr 2026Referencia veterinaria basada en la evidencia
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 |
|---|---|---|---|---|---|
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol A) | 25 mg/kg twice a day, PO with food | PO | q12h | Until clinical endpoints occur (usually 4-9 days) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A) | 25-50 mg/kg per week | PO | Divided in as many doses as possible weekly | Long-term | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol B) | 30-50 mg/kg/day PO with a meal once daily or divided q12h | PO | q24h or q12h | 7-10 days | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol B) | 35-50 mg/kg per week in 2-3 divided doses | PO | Divided weekly | Long-term | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction - Protocol C) | 50 mg/kg divided q12h | PO | q12h | Until water consumption decreases to <100 mL/kg/day or adverse signs observed (usually 3-7 days) | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C) | 50 mg/kg every 7-10 days | PO | Every 7-10 days | Long-term | 🌎 NA |
| Total adrenal ablation (Alternative Protocol D) | 75-100 mg/kg per day for 25 consecutive days, given in 3-4 doses per day with food | PO | Divided q6-8h | 25 days | 🌎 NA |
| Total adrenal ablation (Alternative Protocol E) | 100 mg/kg/day divided twice daily for 30 days | PO | q12h | 30 days | 🌎 NA |
| Palliative medical treatment of adrenal carcinomas or adenomas | 50-75 mg/kg PO in daily divided doses | PO | Divided daily | 10-14 days initially | 🌎 NA |
| Pituitary-dependent hyperadrenocorticism (Induction) | 30-50 mg/kg | PO | q24h | to effect (generally 3-10 days) | 🌍 EU |
| Pituitary-dependent hyperadrenocorticism (Maintenance) | 50 mg/kg | PO | q7-14 days | Ongoing | 🌍 EU |
| Adrenal carcinomas | 50-150 mg/kg | PO | q24h | Ongoing | 🌍 EU |
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol A): Reduce food by 1/3 the day before. Stop therapy if water consumption approaches 60 mL/kg/day, appetite reduces, vomiting, listlessness, or diarrhea occurs.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol A): Adjust based on ACTH stimulation test results.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol B): Goal is basal and post-ACTH cortisol between 1-5 micrograms/dL.
- Pituitary-dependent hyperadrenocorticism (Induction - Protocol C): Max 5-7 days prior to ACTH stim test if water consumption cannot be monitored.
- Pituitary-dependent hyperadrenocorticism (Maintenance - Protocol C): Dose is highly variable (26-330 mg/kg/week).
- Total adrenal ablation (Alternative Protocol D): Requires lifelong prednisone and mineralocorticoid therapy.
- Total adrenal ablation (Alternative Protocol E): Requires cortisone acetate and fludrocortisone acetate supplementation.
- Palliative medical treatment of adrenal carcinomas or adenomas: May increase to 100 mg/kg/day based on ACTH response. Maintenance is 100-200 mg/kg/week.
- Pituitary-dependent hyperadrenocorticism (Induction): Give with/after food high in fat/oil to improve absorption.
- Pituitary-dependent hyperadrenocorticism (Maintenance): Given in 2-3 divided doses as required. Give with/after food high in fat/oil.
- Adrenal carcinomas: Higher doses may become necessary. Give with/after food high in fat/oil.
Gatos
| Indicación | Dosis | Vía | Frecuencia | Duración | Región |
|---|---|---|---|---|---|
| Hyperadrenocorticism | 30-50 mg/kg | PO | q24h | to effect | 🌍 EU |
- Hyperadrenocorticism: Efficacy in cats is very variable, with many showing no response at non-toxic levels. Not recommended.
Hurones
| Indicación | Dosis | Vía | Frecuencia | Duración | Región |
|---|---|---|---|---|---|
| Medical treatment of hyperadrenocorticism | 50 mg per ferret PO once daily for one week, then 50 mg PO 2-3 times per week | PO | q24h then 2-3 times/week | Long-term | 🌎 NA |
- Medical treatment of hyperadrenocorticism: Have a compounding pharmacy make 50 mg capsules. Can be coated with Nutrical.
Las dosis son una referencia clínica para profesionales veterinarios autorizados. Confirme siempre con el prospecto actual y cada paciente individual.
Resumen
El mitotano (también conocido como o,p'-DDD) es un agente citotóxico adrenal utilizado principalmente en medicina veterinaria para el manejo médico del hiperadrenocorticismo dependiente de la hipófisis (PDH) (enfermedad de Cushing), principalmente en perros. Está relacionado estructuralmente con el insecticida DDT (clorofenotano).
Debido a que causa necrosis dirigida de la corteza adrenal, reduce eficazmente la producción excesiva de cortisol. También se utiliza para el tratamiento paliativo del carcinoma adrenal en humanos y perros.
Perla clínica: El tratamiento se divide típicamente en dos fases distintas: una fase de inducción (dosificación diaria para destruir rápidamente el tejido adrenal hiperplásico hasta alcanzar los objetivos clínicos) y una fase de mantenimiento (dosificación semanal o quincenal para prevenir el recrecimiento de la corteza adrenal). Es obligatorio un seguimiento estrecho, ya que un tratamiento excesivo puede conducir a un hipoadrenocorticismo iatrogénico (enfermedad de Addison).
Mecanismo de acción
Mitotane acts as a targeted adrenocortical cytotoxic agent.
- It causes severe, progressive necrosis and atrophy of the zona fasciculata and zona reticularis of the adrenal gland → drastically reducing the synthesis of glucocorticoids (cortisol).
- It relatively spares the zona glomerulosa, meaning mineralocorticoid (aldosterone) synthesis is usually unaffected, though clinically significant effects on aldosterone production can occasionally occur.
- The exact intracellular mechanism of cytotoxicity is not fully understood, but it is believed to involve metabolic activation within the adrenal mitochondria, leading to irreversible binding to cellular macromolecules and subsequent cell death.
Seguridad y advertencias
Contraindicaciones
- Known hypersensitivity to mitotane
- Pregnancy (FDA Category C in humans; Class D in veterinary medicine - embryotoxic/teratogenic)
- Patients that are not eating well (should never be administered to anorexic animals)
- Not recommended in cats (trilostane is more effective and mitotane efficacy is highly variable)
Efectos adversos
- Lethargy
- Ataxia
- Weakness
- Anorexia (loss of appetite)
- Vomiting
- Diarrhea
- Neurologic signs (uncommon)
- Liver changes (congestion, centrolobular atrophy, fatty degeneration)
- Iatrogenic hypoadrenocorticism (requiring long-term glucocorticoid/mineralocorticoid replacement in ~5% of dogs)
- Diarrhoea
- Acute-onset neurological signs (2-3 weeks post-initiation)
Precauciones
Warning: Mitotane should never be administered to animals that are not eating well.
- Diabetes Mellitus: Concurrent diabetes requires close monitoring as insulin requirements may rapidly decrease during initial treatment.
- Organ Dysfunction: Dogs with preexisting renal or hepatic disease should receive the drug with extreme caution and intense monitoring.
- Stress Supplementation: All dogs receiving mitotane therapy must receive additional glucocorticoid supplementation if undergoing physiological stress (e.g., surgery, trauma, acute illness).
- Human Safety: Mitotane is a cytotoxic drug. Caregivers should avoid direct skin contact (wear gloves) and wash hands after administration.
Interacciones farmacológicas
Additive depressant effects may be seen if used concomitantly.
Diabetic dogs receiving insulin may have their insulin requirements rapidly decreased when mitotane therapy is instituted.
Can induce enzymes and reduce the efficacy of mitotane; conversely, mitotane can induce hepatic microsomal enzymes and increase the metabolism of phenobarbital.
Has been demonstrated to block the action of mitotane in dogs; an alternate diuretic is recommended.
Increases the hepatic metabolism of mitotane
Increases the hepatic metabolism of mitotane
Monitorización
- Physical exam and history (especially water consumption, food consumption, and weight)
- ACTH response test (crucial for dose adjustment)
- Serum electrolytes (Na+/K+)
- BUN
- CBC
- Liver enzymes
- Appetite (daily during induction)
- ACTH stimulation test (to monitor treatment efficacy)
- Blood glucose (in diabetic patients)
- Clinical signs of weakness, vomiting, or neurological changes
Farmacocinética
Absorción
Systemic bioavailability in dogs is poor. Oral absorption is significantly enhanced by giving the drug with food (especially food high in oil/fat content). In humans, ~40% is absorbed with peak serum levels at 3-5 hours.
Distribución
Distributes to virtually all tissues in the body. It is highly lipophilic, stored in fat, and does not accumulate in the adrenal glands. A small amount may enter the CSF.
Metabolismo
Metabolized in the liver.
Eliminación
Excreted as metabolites in the urine (10%) and bile (15%) within 24 hours of dosing.
Sobredosis
Because of the drug's toxicity and very long half-life, acute overdosage should be managed aggressively.
- Decontamination: Emptying the stomach and administering activated charcoal and a cathartic should be considered after a recent ingestion.
- Monitoring & Treatment: The patient must be closely monitored. Administer systemic glucocorticoids (e.g., dexamethasone or prednisone) and IV fluids if signs of acute hypoadrenocorticism (Addisonian crisis) develop.
Productos disponibles
Formulaciones
- Tablets
- 500 mg tablet
- 500 mg capsule
Etiquetado para humanos
- Mitotane Tablets (scored): 500 mg (Lysodren)
- Lysodren 500 mg tablet
Estado regulador
Available from Europe for animals that have failed trilostane therapy. POM.
POM (Prescription Only Medicine). Used under the cascade.
Sin datos reguladores para: 🇺🇸 US · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Almacenamiento y estabilidad
Store at room temperature (15-30°C), in tight, light-resistant containers.
Información para el cliente
- Administrar con comida: Siempre administre este medicamento inmediatamente después de una comida (preferiblemente una que contenga algo de grasa o aceite) para asegurar una absorción adecuada.
- Vigile los efectos secundarios: El objetivo de este fármaco es reducir los niveles de cortisol, pero a veces puede reducirlos demasiado. Observe a su mascota de cerca para detectar signos de una "crisis addisoniana", que incluyen letargo, debilidad, vómitos, diarrea o una pérdida repentina del apetito.
- Suspenda si hay enfermedad: Si su mascota deja de comer o muestra cualquiera de los signos anteriores, suspenda la administración del medicamento inmediatamente y contacte a su veterinario. Es posible que se le indique administrar una dosis de rescate de un esteroide (como prednisona).
- Precauciones de seguridad: El mitotano es un fármaco citotóxico potente. Use guantes al manipular las tabletas o lávese bien las manos después. Mantenga el medicamento estrictamente fuera del alcance de niños y otras mascotas.
- Estrés: Su mascota puede necesitar medicación esteroidea adicional durante momentos de estrés, como cirugías, estancias en guarderías o enfermedades agudas. Hable de esto con su veterinario.
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.