Xalkori Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Based on findings from animal studies and its mechanism of action, XALKORI can cause fetal harm when administered to a pregnant woman [see Pharmacology: Mechanism of Action under Actions]. There are no available data on the use of XALKORI during pregnancy. In animal reproduction studies, oral administration of crizotinib in pregnant rats during organogenesis at exposures similar to those expected with the maximum recommended human dose resulted in embryotoxicity and fetotoxicity (see Data as follows). Advise pregnant women of the potential risk to fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data: Animal Data: Crizotinib was administered to pregnant rats and rabbits during organogenesis to study the effects on embryo-fetal development. Post-implantation loss was increased at doses ≥50 mg/kg/day (approximately 0.6 times the recommended human dose based on AUC) in rats. No teratogenic effects were observed in rats at doses up to the maternally toxic dose of 200 mg/kg/day (approximately 2.7 times the recommended human dose based on AUC) or in rabbits at doses of up to 60 mg/kg/day (approximately 1.6 times the recommended human dose based on AUC), though fetal body weights were reduced at these doses.
Lactation: Risk Summary: There is no information regarding the presence of crizotinib or its metabolites in human milk, or the effects on the breastfed child or on milk production. Because of the potential for adverse reactions in breastfed children, advise women not to breastfeed during treatment with XALKORI and for 45 days after the final dose.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify the pregnancy status of females of reproductive potential prior to initiating XALKORI [see Pregnancy as previously mentioned].
Contraception: There are no adequate and well-controlled studies in pregnant women using crizotinib. Women of childbearing potential should be advised to avoid becoming pregnant while receiving crizotinib. Women of childbearing potential who are receiving this drug, or partners of women of childbearing potential receiving this drug, should use adequate contraceptive methods during therapy and for at least 90 days after completing therapy.
Infertility: Based on reproductive organ findings in animals, XALKORI may cause reduced fertility in females and males of reproductive potential. It is not known whether these effects on fertility are reversible [see Pharmacology: Non-Clinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions].