Antineoplastic (Antimetabolite)
PREGNANCY RECOMMENDATION: Contraindicated—1st Trimester Contraindicated (If Combined with Cisplatin)
BREASTFEEDING RECOMMENDATION: Hold Breastfeeding Contraindicated (If Combined with Cisplatin)
PREGNANCY SUMMARY
No reports describing the use of pemetrexed in human pregnancy have been located. The animal data suggest risk based on the only animal species tested. The drug is often combined with cisplatin, another antineoplastic. The drug should be avoided in pregnancy, especially during the 1st trimester. Use after that period may be appropriate if the mother’s condition requires use of the drug, but severe fetal toxicity (e.g., bone marrow suppression observed in adults) is a potential risk.
FETAL RISK SUMMARY
Pemetrexed is a folate analog metabolic inhibitor that is given as a 10-minute IV infusion on day 1 of each 21-day cycle. It is in the same antineoplastic subclass of folic acid antagonists (antimetabolites) as aminopterin, methotrexate, and pralatrexate. Pemetrexed is indicated for nonsquamous non–small-cell lung cancer and mesothelioma either alone or in combination with cisplatin. (See also Cisplatin.) Pemetrexed is not metabolized to an appreciable extent and is primarily eliminated unchanged in the urine. Plasma protein binding is about 81%. In patients with normal renal function, the elimination half-life is 3.5 hours (1).
Reproduction studies have been conducted in mice. Repeated intraperitoneal doses given to mice during organogenesis caused dose-related fetal malformations: incomplete ossification of talus and skull bone at about 1/833rd the recommended IV human dose based on BSA (RHD) and cleft palate at about 1/33rd the RHD. Embryo–fetal deaths and reduced litter sizes also were observed (1).
Carcinogenicity studies have not been conducted with pemetrexed. The drug was clastogenic in an in vivo mouse assay, but was not mutagenic in multiple in vivo tests. IV doses administered to male mice that were about ≥1/1666th the RHD resulted in reduced fertility, hypospermia, and testicular atrophy (1).
It is not known if pemetrexed crosses the human placenta. The molecular weight (about 471 for the nonhydrated form), moderate plasma protein binding, and the elimination half-life suggest that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of pemetrexed during human lactation have been located. The molecular weight (about 471 for the nonhydrated form), moderate (81%) plasma protein binding, and the elimination half-life (3.5 hours) suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown, but severe toxicity such as that observed in patients receiving the drug (e.g., bone marrow suppression, hepatic and renal toxicities, and gastrointestinal disturbances) is a potential complication. Holding breastfeeding for 18–24 hours while “pumping and dumping,” would allow the drug to be nearly eliminated from the mother’s circulation and lessen the risk to a nursing infant. However, breastfeeding is not recommended if the therapy includes cisplatin (see Cisplatin).
Reference
1.Product information. Alimta. Eli Lilly, 2009.