omen who were exposed to procarbazine hydrochloride in combination with other antineoplastic agents during pregnancy. matulane should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. women of childbearing potential should be advised to avoid becoming pregnant. procarbazine hydrochloride is teratogenic in the rat when given at doses approximately 4 to 13 times the maximum recommended human therapeutic dose of 6 mg/kg/day. nonteratogenic effects procarbazine hydrochloride has not been adequately studied in animals for its effects on peri- and postnatal development. however, neurogenic tumors were noted in the offspring of rats given intravenous injections of 125 mg/kg of procarbazine hydrochloride on day 22 of gestation. compounds which inhibit dna, rna and protein synthesis might be expected to have adverse effects on peri- and postnatal development. carcinogenesis, mutagenesis, impairment of fertility carcinogenesis the carcinogenicity of procarbazine hydrochloride in mice, rats and monkeys has been reported in a considerable number of studies. instances of a second nonlymphoid malignancy, including lung cancer and acute myelocytic leukemia, have been reported in patients with hodgkin’s disease treated with procarbazine in combination with other chemotherapy and/or radiation. the risks of secondary lung cancer from treatment appear to be multiplied by tobacco use. the international agency for research on cancer (iarc) considers that there is “sufficient evidence” for the human carcinogenicity of procarbazine hydrochloride when it is given in intensive regimens which include other antineoplastic agents but that there is inadequate evidence of carcinogenicity in humans given procarbazine hydrochloride alone. mutagenesis procarbazine hydrochloride has been shown to be mutagenic in a variety of bacterial and mammalian test systems. impairment of fertility azoospermia and antifertility effects associated with procarbazine hydrochloride administration in combination with other chemotherapeutic agents for treating hodgkin’s disease have been reported in human clinical studies. since these patients received multicombination therapy, it is difficult to determine to what extent procarbazine hydrochloride alone was involved in the male germcell damage. the usual segment i fertility/reproduction studies in laboratory animals have not been carried out with procarbazine hydrochloride. however, compounds which inhibit dna, rna and/or protein synthesis might be expected to have adverse effects on gametogenesis. unscheduled dna synthesis in the testis of rabbits and decreased fertility in male mice treated with procarbazine hydrochloride have been reported.

y stools. hemorrhage or bleeding tendencies. bone marrow depression often occurs 2 to 8 weeks after the start of treatment. if leukopenia occurs, hospitalization of the patient may be needed for appropriate treatment to prevent systemic infection.

upon evidence of hematologic or other toxicity (see precautions section), the drug should be discontinued until there has been satisfactory recovery. after toxic side effects have subsided, therapy may then be resumed at the discretion of the physician, based on clinical evaluation and appropriate laboratory studies, at a dosage of 1 to 2 mg/kg/day. pediatric patients: very close clinical monitoring is mandatory. undue toxicity, evidenced by tremors, coma and convulsions, has occurred in a few cases. dosage, therefore, should be individualized. the following dosage schedule is provided as a guideline only. fifty (50) mg per square meter of body surface per day is recommended for the first week. dosage should then be maintained at 100 mg per square meter of body surface per day until maximum response is obtained or until leukopenia or thrombocytopenia occurs. when maximum response is attained, the dose may be maintained at 50 mg per square meter of body surface per day. upon evidence of hematologic or other toxicity (see precautions section), the drug should be discontinued until there has been satisfactory recovery, based on clinical evaluation and appropriate laboratory tests. after toxic side effects have subsided, therapy may then be resumed. procedures for proper handling and disposal of anticancer drugs should be considered. several guidelines on this subject have been published. 1-6 there is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

in, including myalgia and arthralgia; tremors. psychiatric hallucinations, depression, apprehension, nervousness, confusion, nightmares. endocrine gynecomastia in prepubertal and early pubertal boys. miscellaneous intercurrent infections, hearing loss, pyrexia, diaphoresis, lethargy, weakness, fatigue, edema, chills, insomnia, slurred speech, hoarseness, drowsiness. second nonlymphoid malignancies (including lung cancer, acute myelocytic leukemia and malignant myelosclerosis) and azoospermia have been reported in patients with hodgkin’s disease treated with procarbazine in combination with other chemotherapy and/or radiation. the risks of secondary lung cancer from treatment appear to be multiplied by tobacco use.

tely studied in animals for its effects on peri- and postnatal development. however, neurogenic tumors were noted in the offspring of rats given intravenous injections of 125 mg/kg of procarbazine hydrochloride on day 22 of gestation. compounds which inhibit dna, rna and protein synthesis might be expected to have adverse effects on peri- and postnatal development.

nd ch 4 and possibly hydrazine, whereas the aldehyde is oxidized to n -isopropylterephthalamic acid, which is excreted in the urine. procarbazine is rapidly and completely absorbed. following oral administration of 30 mg of 14 c-labeled procarbazine, maximum peak plasma radioactive concentrations were reached within 60 minutes. after intravenous injection, the plasma half-life of procarbazine is approximately 10 minutes. approximately 70% of the radioactivity is excreted in the urine as n -isopropylterephthalamic acid within 24 hours following both oral and intravenous administration of 14 c-labeled procarbazine. procarbazine crosses the blood-brain barrier and rapidly equilibrates between plasma and cerebrospinal fluid after oral administration.

est systems. impairment of fertility azoospermia and antifertility effects associated with procarbazine hydrochloride administration in combination with other chemotherapeutic agents for treating hodgkin’s disease have been reported in human clinical studies. since these patients received multicombination therapy, it is difficult to determine to what extent procarbazine hydrochloride alone was involved in the male germcell damage. the usual segment i fertility/reproduction studies in laboratory animals have not been carried out with procarbazine hydrochloride. however, compounds which inhibit dna, rna and/or protein synthesis might be expected to have adverse effects on gametogenesis. unscheduled dna synthesis in the testis of rabbits and decreased fertility in male mice treated with procarbazine hydrochloride have been reported.