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Procarbazine is available in capsule form. The primary use of this drug is as an antineoplastic agent in the treatment of advanced Hodgkin’s disease, and oat-cell carcinoma of the lung. The hydrochloride com- pound is used in treatment. The FDA approved use of pro- carbazine hydrochloride in 1969 and indicated that the drug should be used as an adjunct to standard therapy. Possible exposure occurs during manufacture of the drug and direct exposure during its subsequent administration to patients. Some of the metabolites of procarbazine hydrochloride are both carcinostatic and carcinogenic.

Move victim to fresh air. Call 911 or emergency medical service. Give artificial respiration if victim is not breathing. Do not use mouth-to-mouth method if victim ingested or inhaled the substance; give artificial respira- tion with the aid of a pocket mask equipped with a one-way valve or other proper respiratory medical device. Administer oxygen if breathing is difficult. Remove and isolate contaminated clothing and shoes. In case of contact with substance, immediately flush skin or eyes with run- ning water for at least 20 minutes. For minor skin contact, avoid spreading material on unaffected skin. Keep victim warm and quiet. Effects of exposure (inhalation, ingestion or skin contact) to substance may be delayed. Ensure that medical personnel are aware of the material(s) involved and take precautions to protect themselves. Medical obser- vation is recommended for 24?48 hours after breathing overexposure, as pulmonary edema may be delayed. As first aid for pulmonary edema, a doctor or authorized paramedic may consider administering a drug or other inhalation therapy.

UN2811 Toxic solids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required.

Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Keep away from alkaline materials, strong bases, strong acids, oxoacids, epoxides.

Procarbazine is a white to pale yellow crystal- line powder with a slight odor.

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quanti- ties shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.

antibacterial

Procarbazine was initially synthesized as an MAO inhibitor. However, it was discovered later on that it has ability to act as an alkylating agent and inhibit DNA, RNA, and protein synthesis. Along with this, there is an opinion that procarbazine accumulates in cancerous tissue and generates peroxide and hydroperoxide radicals in cells, which imitates the effect of ionizing radiation. It is used for malignant tumors of lymphatic tissue, brain tumors, lung tumors, and Hodgkin’s disease. A synonym of this drug is natulan.

ChEBI: A benzamide obtained by formal condensation of the carboxy group of 4-[(2-methylhydrazino)methyl]benzoic acid with the amino group of isopropylamine. An antineoplastic chemotherapy drug used for treatment of Hodgkin's lymphoma. Metabolism yields azo-procar azine and hydrogen peroxide, which results in the breaking of DNA strands.

Procarbazine (Matulane) may autooxidize spontaneously, and during this reaction hydrogen peroxide and hydroxyl free radicals are generated. These highly reactive products may degrade DNA and serve as one mechanism of procarbazine-induced cytotoxicity. Cell toxicity also may be the result of a transmethylation reaction that can occur between the N-methyl group of procarbazine and the N7 position of guanine.

Procarbazine exhibits an interesting interaction with ethanol, resulting in headaches, diaphoresis, and facial erythema; patients taking this drug should be forewarned to abstain from alcohol. Procarbazine is also a monoamine oxidase (MAO) inhibitor and may potentiate the effects of drugs that are substrates for this enzyme.

Matulane (Sigma-Tau).

Procarbazine is rapidly absorbed after oral administration and has a plasma half-life of only 10 minutes. The drug crosses the blood-brain barrier, reaching levels in CSF equal to those obtained in plasma. Metabolism is extensive and complex. Urinary excretion accounts for 70% of the procarbazine and its metabolites lost during the first 24 hours after drug administration.

When originally tested as a single agent in advanced Hodgkin’s disease, procarbazine produced tumor regression responses that were brief, usually lasting only 1 to 3 months. The combination of procarbazine with mechlorethamine, vincristine, and prednisone in the MOPP regimen, however, resulted in an 81% complete remission rate in Hodgkin’s disease. Most of these patients are considered cured. Procarbazine is also used in various combination chemotherapy protocols for non- Hodgkin’s lymphomas and small cell anaplastic (oat cell) carcinoma of the lung. Limited antitumor effects have been observed against multiple myeloma, melanoma, and non–oat cell lung cancers.

The major side effects associated with procarbazine therapy are nausea and vomiting, leukopenia, and thrombocytopenia. Skin rashes have been reported, as have rare cases of allergic interstitial pneumonia. Procarbazine administration produces a high degree of chromosomal breakage, and the compound is mutagenic, teratogenic, and carcinogenic in experimental systems.
Procarbazine may potentiate the effects of tranquilizers and hypnotics. Hypertensive episodes can result if procarbazine is administered simultaneously with adrenomimetic drugs or with tyramine-containing foods. Rarely, a reaction to alcohol similar to that provoked by disulfiram may occur.

Procarbazine, 1-methyl-2-(n-isopropylcarbamoylbenzyl)-hydrazine (30.6.8), is synthesized from 1,2-bis-(benzyloxycarbonyl)-1-methylhydrazine, which is alkylated by the methyl ester of 4-bromomethylbenzoic acid in the presence of sodium hydride, which forms 1,2-bis(benzyloxycarbonyl)-1-methyl-2-(p-carbomethoxy)benzylhydrazine (30.6.6). The carbomethoxy group of this molecule is hydrolyzed by sodium hydroxide, and the resulting carboxyl group is transformed into a acid chloride group, followed by a reaction of this product with isopropylamine gives 1,2-bis-(binzyloxycarbonyl)-1-methyl-2-(p-isopropylcarbamoyl)benzylhydrazine (30.6.7). Hydrolyzis of the benzyloxycarbonyl group in the resulting compound with hydrogen bromide in acetic acid gives the desired procarbazine (30.6.8).

Potentially hazardous interactions with other drugs
Alcohol: may produce a disulfiram reaction.
Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).

Procarbazine and procarbazine hydrochloride are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals. The names “procarbazine” and “procarbazine hydrochloride” are used interchangeably in published studies; because only procarbazine hydrochloride is produced, it has been assumed that procarbazine hydrochloride was the substance under study.

Procarbazine is metabolised to an active alkylating agent by microsomal enzymes in the liver and kidneys and only about 5% is excreted unchanged in the urine. The remainder is oxidised to N-isopropylterephthalamic acid and excreted in the urine, with up to 70% of a dose recovered in the urine after 24 hours.