PREGNANCY RECOMMENDATION: Contraindicated—1st Trimester
BREASTFEEDING RECOMMENDATION: Contraindicated
Although combined with other antineoplastics, structural anomalies have been observed when procarbazine was used in the 1st trimester. The drug is best avoided during organogenesis.
FETAL RISK SUMMARY
The use of procarbazine, in combination with other antineoplastic agents, during pregnancy has been described in nine patients, five during the 1st trimester (1–8). One of the 1st trimester exposures was electively terminated, but no details on the fetus were given (5). Congenital malformations were observed in the remaining four 1st trimester exposures (1–4):
Multiple hemangiomas (1)
Oligodactyly of both feet with webbing of third and fourth toes, four metatarsals on left, three on right, bowing of right tibia, cerebral hemorrhage, spontaneously aborted at 24 weeks’ gestation (2)
Malformed kidneys—markedly reduced size and malposition (3)
Small secundum atrial septal defect, intrauterine growth restriction (4)
A patient in her 12th week of pregnancy received procarbazine, 50 mg daily, in error for 30 days when she was given the drug instead of an iron/vitamin supplement (6). A normal 3575-g male infant was delivered at term.
Long-term studies of growth and mental development in offspring exposed to procarbazine during the 2nd trimester, the period of neuroblast multiplication, have not been conducted (9). Data from one review indicated that 40% of the infants exposed to anticancer drugs were of low birth weight (10). This finding was not related to the timing of exposure.
Procarbazine is mutagenic and carcinogenic in animals (11). In combination with other antineoplastic drugs, procarbazine may produce gonadal dysfunction in males and females (12–17). Ovarian and testicular function may return to normal, with successful pregnancies possible, depending on the patient’s age at the time of therapy and the total dose of chemotherapy received (16–20).
It is not known if procarbazine crosses the human placenta. The molecular weight (about 222 for the free base) is low enough that exposure of the embryo–fetus should be expected.
Occupational exposure of the mother to antineoplastic agents during pregnancy may present a risk to the fetus. A position statement from the National Study Commission on Cytotoxic Exposure and a research article involving some antineoplastic agents are presented in the monograph for cyclophosphamide (see Cyclophosphamide).
No reports describing the use of procarbazine during lactation have been located. The molecular weight (about 222 for the free base) is low enough that excretion into breast milk should be expected. Because of the potential for tumorigenicity, women receiving this drug should not nurse (21).
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21.Product information. Matulane. Sigma-Tau Pharmaceuticals, 2000.