Antineoplastic
PREGNANCY RECOMMENDATION: Contraindicated
BREASTFEEDING RECOMMENDATION: Contraindicated
PREGNANCY SUMMARY
No reports describing the use of eribulin in human pregnancy have occurred. Although developmental toxicity occurred in rats at maternal toxic doses, the doses were much less than the recommended human dose. Because of the risk for severe toxicity in an embryo and/or a fetus, eribulin should not be used in pregnancy.
FETAL RISK SUMMARY
Eribulin is a nontaxane microtubule dynamics inhibitor that is given IV on days 1 and 8 of a 21-day cycle. It is indicated for the treatment of patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens for the treatment of metastatic disease. There are no major metabolites of eribulin. Plasma protein binding is in the range of 49%–65%. The mean elimination half-life is about 40 hours (1).
Reproduction studies have been conducted in rats. In this species, IV doses were given during organogenesis (gestation days 8, 10, and 12) that were about 0.04–0.64 times the recommended human dose based on BSA (RHD). At the highest dose, abortions and severe external or soft-tissue malformations were observed. The malformations included the absence of a lower jaw, tongue, stomach, and spleen. At 0.43 times the RHD, increased embryo–fetal death/resorption, reduced fetal weights, and minor skeletal anomalies consistent with developmental delay were noted. However, at doses ≥0.43 times the RHD, maternal toxicity that included enlarged spleen, reduced maternal weight gain, and decreased food consumption occurred (1).
Studies of carcinogenicity have not been conducted. Eribulin was not mutagenic in bacterial assays but was mutagenic in other assays and was clastogenic in one assay. Although fertility studies have not been conducted, dog and rat toxicology studies have observed testicular toxicity in both species suggesting that the drug may compromise male fertility (1).
It is not known if eribulin crosses the human placenta. The molecular weight (about 730 for the free base), lack of metabolism, moderate protein binding, and long half-life suggest that the drug will cross to the embryo–fetus.
BREASTFEEDING SUMMARY
No reports describing the use of eribulin during human lactation have been located. The molecular weight (about 730 for the free base), lack of metabolism, moderate protein binding, and long half-life suggest that the drug will be excreted into breast milk. Moreover, as a basic drug, higher concentrations of eribulin in milk compared with the plasma may occur. The effect of this exposure on a nursing infant is unknown but there is potential for severe toxicity. Consequently, breastfeeding during therapy with this agent should be considered contraindicated.
Reference
1.Product Information. Halaven. Eisai, 2010.