Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of pentostatin in human pregnancy have been located. The animal reproduction data suggest risk, but the absence of human pregnancy experiences prevents a complete assessment of the embryo–fetal risk. However, pentostatin inhibits the synthesis of DNA and RNA, and increases DNA damage. Because hairy cell leukemia usually has an indolent course, deferring treatment until after delivery may be appropriate (1).
FETAL RISK SUMMARY
Pentostatin is a hydrophilic, cytotoxic agent that is classified as an antimetabolite. It is in the same antineoplastic subclass of purine analogs and related agents as cladribine, clofarabine, fludarabine, mercaptopurine, and thioguanine. Pentostatin is indicated as single-agent treatment for both untreated and alpha-interferon-refractory hairy cell leukemia patients with active disease as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease-related symptoms. It inhibits DNA and RNA synthesis and causes increased DNA damage. The agent is partially metabolized before urinary excretion, but the activity of the metabolites (assumed to be inactive) has not been stated. Plasma protein binding is very low (about 4%) and the terminal elimination half-life is 5.7 hours (2).
Reproduction studies have been conducted in rats, mice, and rabbits. In rats, daily IV doses (days 6–15) that were about (based on total dose) 1.5 and 11 times the recommended human dose given every 2 weeks based on BSA (RHD) caused maternal toxicity and the highest dose was associated with various fetal skeletal malformations. Other defects observed in rats were omphalocele at about 0.75 times the RHD, gastroschisis at about 11 and 15 times the RHD, and flexure defect of the hindlimbs at about 11 times the RHD. The drug was teratogenic (defects not specified) in mice given a single intraperitoneal dose that was about 1.5 times the RHD. No teratogenicity was observed in rabbits with daily IV doses (days 6–18) that were about (based on total dose) 0.05–0.2 times the RHD. However, maternal toxicity, abortions, early deliveries, and deaths occurred in all dose groups (2).
Carcinogenic studies have not been conducted. Pentostatin was mutagenic in some assays but not others, and was clastogenic in one test. Fertility studies have not been conducted, but in a 5-day IV toxicity study in dogs, mild seminiferous tubular degeneration was observed (2).
It is not known if pentostatin crosses the human placenta. The molecular weight (about 268), low plasma protein binding, and moderate elimination half-life suggest that exposure of the embryo–fetus will occur.
BREASTFEEDING SUMMARY
No reports describing the use of pentostatin during human lactation have been located. The molecular weight (about 268), low plasma protein binding (about 4%), and moderate elimination half-life (5.7 hours) suggest that the drug will be excreted into breast milk. However, the hydrophilic properties of the drug may limit excretion. The effect of this exposure on a nursing infant is unknown, but the drug has caused severe toxicity in treated patients, such as gastrointestinal upset, rash, fever, and fatigue. If a woman elects to breastfeed in spite of this potential risk, pumping and dumping for about 30 hours after a dose should significantly reduce the exposure.
References
1.Robak T. Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Cancer Treat Rev 2006;32:365–76.
2.Product information. Pentostatin for injection. Bedford Laboratories, 2006.