Antineoplastic (Antimetabolite)
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of pralatrexate in human pregnancy have been located. The animal data suggest risk based on the two animal species studied. Although the drug did not cause structural anomalies, it did cause embryo and fetal death. Moreover, pralatrexate is a folic acid antagonist in the same subclass of antimetabolites as aminopterin and methotrexate, agents known to cause embryo–fetal harm. Another agent in this subclass is pemetrexed. Pralatrexate should be avoided in pregnancy. If indicated during pregnancy for maternal benefit, the mother should be informed of the potential risk to her embryo and/or fetus.
FETAL RISK SUMMARY
Pralatrexate is a folate analog metabolic inhibitor that is given as weekly IV push doses. It is in the same antineoplastic subclass of folic acid antagonists (antimetabolites) as methotrexate and pemetrexed. Pralatrexate is indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma. The drug is partially metabolized (about a third of a dose excreted unchanged in urine), but the amount of plasma protein binding was not specified. The terminal elimination half-life is 12–18 hours (1).
Reproduction studies have been conducted in rats and rabbits. In rats, daily doses given on gestation days 7–20 that were about 1.2% of the clinical dose based on BSA (CD) were embryotoxic and fetotoxic. A dose-dependent decrease in fetal viability manifested as an increase in early, late, and total resorptions was observed. There was also a dose-dependent increase in postimplantation loss. In rabbits, similar daily doses given on gestation days 8–21 caused abortion and fetal lethality. The toxicity was manifested as early and total resorptions, postimplantation loss, and a decrease in the total number of live fetuses (1).
Neither carcinogenicity nor fertility studies have been conducted with pralatrexate. The drug was not mutagenic in multiple tests (1).
It is not known if pralatrexate crosses the human placenta. The molecular weight (about 477) and the long terminal elimination half-life suggest that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of pralatrexate during human lactation have been located. The molecular weight (about 477) and the long terminal elimination half-life (12–18 hours) suggest that the drug will be excreted into breast milk. Moreover, the long half-life makes a “pump and dump” method impractical (i.e., the mother would have to wait about 60–90 hours to eliminate most of the drug from her circulation). The effect of this exposure on a nursing infant is unknown, but serious toxicities observed in adults (e.g., pyrexia, bone marrow depression, mucositis, nausea, and vomiting) are potential complications. Based on the potential risk, the best course is not to breastfeed.
Reference
1.Product information. Folotyn. Allos Therapeutics, 2009.