Procarbazine
**Procarbazine** is an atypical alkylating antineoplastic agent primarily utilized in veterinary medicine as a component of the **MOPP** (Mechlorethamine, Vincristine, Procarbazine, Prednisone) or **LOPP** chemotherapy protocols for the treatment of relapsed or resistant lymphoma in dogs and cats. > **Clinical Pearl**: Unlike many other chemotherapeutic agents, procarbazine is highly lipophilic and readily crosses the **blood-brain barrier (BBB)**. This unique property makes it highly efficacious in treating central nervous system (CNS) neoplasms and inflammatory conditions, most notably **Granulomatous Meningoencephalitis (GME)** in dogs. Additionally, procarbazine exhibits weak **Monoamine Oxidase Inhibitor (MAOI)** activity, which necessitates strict caution regarding drug interactions (e.g., tricyclic antidepressants, sympathomimetics) and dietary restrictions (tyramine-rich foods) to prevent hypertensive crises.
Mecanismo: Procarbazine is a prodrug that requires hepatic and renal metabolism to become active. Its exact mechanism is complex and multifaceted: - **Hepatic Metabolism** → Procarbazine is oxidized to **azo-procarbazine** and further metabolized to yield **methyl radicals** and **hydrogen peroxide**. - **DNA Alkylation** → The methyl radicals directly methylate nucleic acids, causing DNA strand breakage and inhibiting the synthesis of DNA, RNA, and proteins. - **Oxidative Stress** → The auto-oxidation process generates hydrogen peroxide, which directly induces oxidative damage to DNA. - **MAO Inhibition** → As an off-target effect, it inhibits the enzyme **monoamine oxidase (MAO)**, preventing the breakdown of monoamines like serotonin, norepinephrine, and dopamine.
Dosificación por especie
- MOPP lymphoma rescue · 50 mg/m2 or 10 mg (total dose per cat) · PO · once daily for the first 14 days of the treatment cycle · 14 days · Used as part of a protocol in combination with other antineoplastic agents.
- Lymphoma rescue (MOPP protocol) · 50 mg/m2 · PO · once daily for the first 14 days of the treatment cycle · 14 days · Used as part of a protocol in combination with other antineoplastic agents.
- Granulomatous meningoencephalitis (GME) · 25-50 mg/m2 · PO · once daily initially, then every other day · Initially given with prednisone treatment. After the first month, attempt to reduce to every other day. Monitor CBC weekly for the first month.
Las dosis son una referencia clínica para veterinarios colegiados. Confirme siempre con la ficha técnica vigente y el paciente individual.
Vías de administración
Contraindicaciones
- Known hypersensitivity to procarbazine
- Inadequate bone marrow reserve
Efectos adversos
- Nausea and vomiting
- Hepatotoxicity
- Myelosuppression (thrombocytopenia, leukopenia)
- Hemorrhagic gastritis
- CNS effects (sedation, agitation)
- Peripheral neuropathy (loss of tendon reflexes, paresthesias, myalgia)
Interacciones farmacológicas
- Alcohol/Ethanol · May cause severe nausea and vomiting (disulfiram-like reaction).
- CNS Depressant Drugs (barbiturates, opiates, antihistamines, phenothiazines) · Procarbazine can cause CNS depression; concurrent use can lead to severe depression. Coma and death have been reported with opiates.
- Foods with high tyramine content (aged cheese, yogurt) · Serious hypertension may result due to procarbazine's MAOI activity.
- Sympathomimetics (phenylpropanolamine, etc.) · Serious hypertension may result due to procarbazine's MAOI activity.
- Tricyclic Antidepressants (clomipramine, amitriptyline) · Do not use concurrently due to MAOI activity; risk of serotonin syndrome or hypertensive crisis.
Monitorización
- Baseline: CBC, hepatic and renal function, urinalysis
- Repeat CBC at least once weekly for the first month of treatment, and then monthly thereafter
- Monitor for signs of neurotoxicity or severe GI distress
Sobredosis
The LD50 for laboratory animals ranges from 150 mg/kg (rabbits) to 1.3 grams/kg (mice). - **Treatment**: Treat overdoses aggressively to remove the drug from the gut if the overdose occurred within an hour or two (e.g., induction of emesis, activated charcoal). - **Anticipated Effects**: Extensions of the drug's adverse effect profile, including severe GI distress, profound bone marrow suppression, and CNS effects. - **Management**: Monitor closely and provide supportive care as necessary. Contact an animal poison control center for further guidance.
La referencia de fármacos de VetSheet está destinada a veterinarios colegiados como apoyo a la decisión clínica, no sustituye el juicio profesional ni la ficha técnica vigente del fabricante.