Procarbazine
Procarbazine hydrochloride
Also known as: Matulane · Natulanar · Ibenzemethyzin · NSC-77213 · Ro-46467/1 · MIH · N-Methylhydrazine
Reviewed by the VetSheet Veterinary TeamUpdated Apr 5, 2026Evidence-based veterinary reference
This dose is based on body surface area (mg/m²). Convert body weight to body surface area before dosing.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Dosing by species
🌎 NA — North America🌍 EU — Europe
Dogs
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| Lymphoma rescue (MOPP protocol) | 50 mg/m2 | PO | once daily for the first 14 days of the treatment cycle | 14 days | 🌎 NA |
| Granulomatous meningoencephalitis (GME) | 25-50 mg/m2 | PO | once daily initially, then every other day | — | 🌎 NA |
- Lymphoma rescue (MOPP protocol): Used as part of a protocol in combination with other antineoplastic agents.
- Granulomatous meningoencephalitis (GME): Initially given with prednisone treatment. After the first month, attempt to reduce to every other day. Monitor CBC weekly for the first month.
Cats
| Indication | Dose | Route | Frequency | Duration | Region |
|---|---|---|---|---|---|
| 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 | 🌎 NA |
- MOPP lymphoma rescue: Used as part of a protocol in combination with other antineoplastic agents.
Doses are a clinical reference for licensed veterinary professionals. Always confirm against the current label and the individual patient.
Overview
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 of action
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.
Safety & warnings
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)
Precautions
Hazardous Drug: Procarbazine is a cytotoxic agent and a known teratogen (FDA Category D). Strict safe handling protocols must be followed by both veterinary staff and pet owners.
- Use with extreme caution in patients with impaired renal or hepatic function.
- Use with extreme caution when co-administering with other CNS depressant drugs.
- Because it is often used in combination protocols (e.g., MOPP), myelosuppression and GI effects may be significantly enhanced.
Drug interactions
May cause severe nausea and vomiting (disulfiram-like reaction).
Procarbazine can cause CNS depression; concurrent use can lead to severe depression. Coma and death have been reported with opiates.
Serious hypertension may result due to procarbazine's MAOI activity.
Serious hypertension may result due to procarbazine's MAOI activity.
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
Pharmacokinetics
Absorption
Well absorbed after oral administration.
Distribution
Rapidly equilibrates between the CSF and plasma. Peak levels in plasma occur in about 1 hour; in the CSF, about 30-90 minutes after dosing.
Metabolism
Almost entirely metabolized in the liver and kidney into cytotoxic products.
Elimination
Metabolic products are excreted in the urine.
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.
Available products
Formulations
- Capsules: 50 mg
- Compounded oral suspension (oil-based)
Human-labeled
- Procarbazine HCl Capsules: 50 mg (Matulane)
Regulatory status
No regulatory data for: 🇺🇸 US · 🇪🇺 EU · 🇬🇧 UK · 🇭🇰 HK · 🇹🇼 TW · 🇯🇵 JP · 🇰🇷 KR · 🇦🇺 AU
Storage & stability
Store capsules in airtight containers, protected from light at temperatures less than 40°C (preferably between 15-30°C / 59-86°F). Compounded oil-based solutions (e.g., using sesame oil and silica gel) are typically assigned an expiration date of 30 days.
Client information
CRITICAL SAFETY WARNING: Procarbazine is a chemotherapy drug. Strict safety measures must be taken at home to protect human family members.
- Safe Handling: Always wear disposable gloves when handling this medication. Wash your hands thoroughly after giving the dose.
- Waste Management: Avoid direct contact with your pet's saliva, vomit, urine, or feces for several days after administration. Clean up accidents wearing gloves and dispose of waste in sealed plastic bags.
- When to Call the Vet: Contact your veterinarian immediately if your pet shows signs of toxicity, including vomiting, lack of appetite, diarrhea, abnormal bleeding or bruising, severe depression, agitation, sores in the mouth, or lameness.
- Pregnancy Warning: Pregnant women, nursing mothers, and individuals trying to conceive should not handle this medication.
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.