Procarbazine hydrochloride (MIH, N-Methylhydrazine)
Procarbazine hydrochloride (Matulane)
Procarbazine hydrochloride
(pro- KAR-bah-zeen)
Pregnancy Category: D Matulane Natulan (Abbreviation: PCB) (Rx)

Classification: Antineoplastic, miscellaneous

See Also: See also Antineoplastic Agents .

Action/Kinetics: May inhibit synthesis of protein, RNA, and DNA and inhibit transmethylation of methyl groups of methionine into t-RNA. Absences of t-RNA could result in cessation of protein synthesis and subsequently DNA and RNA synthesis. Also, hydrogen peroxide formed during auto-oxidation of the drug may attack protein sulfhydryl groups found in residual protein that is tightly bound to DNA. Rapidly absorbed from GI tract. Drug equilibrates between plasma and CSF (peak CSF levels occur within 30-90 min and peak plasma levels occur within 60 min). t 1/2, after IV: 10 min. Metabolized in the liver and kidneys to cytotoxic products. About 70% eliminated in urine, mostly as metabolites, after 24 hr.

Uses: As an adjunct in the treatment of Hodgkin's disease (stage III and stage IV) as part of MOPP (nitrogen mustard, vincristine, procarbazine, prednisone) or ChIVPP (chlorambucil, vinblastine, procarbazine, prednisone) therapies. Investigational: Non-Hodgkin's lymphomas, malignant melanoma, primary brain tumors, lung cancer, multiple myeloma, polycythemia vera.

Contraindications: Inadequate bone marrow reserve as shown by bone marrow aspiration (i.e., in clients with leukopenia, thrombocytopenia, or anemia). Lactation. Hypersensitivity to drug.

Special Concerns: Use with caution in impaired kidney or liver function. Due to the possibility of tremors, convulsions, and coma, close monitoring is necessary when used in children.

Side Effects: GI: N&V;, anorexia, stomatitis, dry mouth, dysphagia, abdominal pain, hematemesis, melena, diarrhea, constipation. CNS: Paresthesias, neuropathies, headache, dizziness, depression, apprehension, nervousness, insomnia, nightmares, hallucinations, falling, weakness, fatigue, lethargy, drowsiness, unsteadiness, ataxia, foot drop, decreased reflexes, tremors, confusion, coma, convulsions. CV: Hypotension, tachycardia, syncope. Respiratory: Pleural effusion, pneumonitis, cough. Hematologic: Leukopenia, anemia, thrombocytopenia, pancytopenia, eosinophilia, hemolytic anemia petechiae, purpura, epistaxis, hemoptysis. GU: Hematuria, urinary frequency, nocturia. Dermatologic: Dermatitis, pruritus, rash, urticaria, herpes, hyperpigmentation, flushing, alopecia. Ophthalmic: Retinal hemorrhage, nystagmus, photophobia, diplopia, inability to focus, papilledema. Hepatic: Jaundice, hepatic dysfunction. Miscellaneous: Gynecomastia in prepubertal and early pubertal boys, pain, myalgia and arthralgia, pyrexia, diaphoresis, chills, intercurrent infections, edema, hoarseness, generalized allergic reactions, hearing loss, slurred speech, second nonlymphoid malignancies (including acute myelocytic leukemia, malignant myelosclerosis) and azoospermia in those treated with procarbazine combined with other chemotherapy or radiation.

Overdose Management: Symptoms: N&V;, diarrhea, enteritis, hypotension, tremors, seizures, coma, hematologic and hepatic toxicity. Treatment: Induce vomiting or undertake gastric lavage. IV fluids. Perform trequent blood counts and LFTs.

Drug Interactions: Alcohol / Antabuse-like reaction Antihistamines / Additive CNS depression Antihypertensive drugs / Additive CNS depression Barbiturates / Additive CNS depression Chemotherapy / Depressed bone marrow activity Digoxin / Digoxin plasma levels Guanethidine / Excitation and hypertension Hypoglycemic agents, oral / Hypoglycemic effect Insulin / Hypoglycemic effect Levodopa / Flushing and hypertension within 1 hr of administration MAO inhibitors / Possibility of hypertensive crisis Methyldopa / Excitation and hypertension Narcotics / Significant CNS depression possible deep coma/death Phenothiazines / Additive CNS depression; also, possible hypertensive crisis Sympathomimetics, indirectly acting / Possibility of hypertensive crisis Tricyclic antidepressants / Possible toxic and fatal reactions, including excitability, fluctuations in BP, seizures, and coma Tyramine-containing foods / Possibility of hypertensive crisis

How Supplied: Capsule: 50 mg

Dosage
?Capsules When used alone.
Adults: 2-4 mg/kg/day for first week; then, 4-6 mg/kg/day until leukocyte count falls below 4,000/mm ³ or platelet count falls below 100,000/mm ³. If toxic symptoms appear, discontinue drug and resume treatment at rate of 1-2 mg/kg/day; maintenance: 1-2 mg/kg/day. Children, highly individualized: 50 mg/m ²/day for first week; then 100 mg/m ² (to nearest 50 mg) until maximum response obtained or until leukopenia or thrombocytopenia occurs. When maximum response is reached, maintain the dose at 50 mg/m ²/day.
When used in combination with other antineoplastic drugs (e.g., MOPP or ChIVPP therapies).
100 mg/m ² for 14 days.