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.
Mechanism: 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.
Dosing by species
- 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.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Routes of administration
Contraindications
- Known hypersensitivity to procarbazine
- Inadequate bone marrow reserve
Adverse effects
- Nausea and vomiting
- Hepatotoxicity
- Myelosuppression (thrombocytopenia, leukopenia)
- Hemorrhagic gastritis
- CNS effects (sedation, agitation)
- Peripheral neuropathy (loss of tendon reflexes, paresthesias, myalgia)
Drug interactions
- 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.
Monitoring
- 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
Overdose
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.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturer’s current label.