Zykadia Use In Pregnancy & Lactation

Pregnancy: Risk Summary: Based on animal studies and its mechanism of action [see Pharmacology: Mechanism of Action under Actions], ZYKADIA can cause fetal harm when administered to a pregnant woman. The limited available data on the use of ZYKADIA in pregnant women are insufficient to inform a risk. Administration of ceritinib to rats and rabbits during the period of organogenesis at maternal plasma exposures below the recommended human dose caused increases in skeletal anomalies in rats and rabbits (see Data as follows). Advise a pregnant woman of the potential risk to a fetus.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies are 2% to 4% and 15% to 20%, respectively.
Data: Animal Data: In an embryo-fetal development study in which pregnant rats were administered daily doses of ceritinib during organogenesis, dose-related skeletal anomalies were observed at doses as low as 50 mg/kg (less than 0.5-fold the human exposure by AUC at the recommended dose). Findings included delayed ossifications and skeletal variations.
In pregnant rabbits administered ceritinib daily during organogenesis, dose-related skeletal anomalies, including incomplete ossification, were observed at doses equal to or >2 mg/kg/day (approximately 0.015-fold the human exposure by AUC at the recommended dose). A low incidence of visceral anomalies, including absent or malpositioned gallbladder and retroesophageal subclavian cardiac artery, was observed at doses equal to or >10 mg/kg/day (approximately 0.13-fold the human exposure by AUC at the recommended dose). Maternal toxicity and abortion occurred in rabbits at doses of 35 mg/kg or greater. In addition, embryolethality was observed in rabbits at a dose of 50 mg/kg.
Lactation: Risk Summary: There are no data regarding the presence of ceritinib or its metabolites in human milk, the effects of ceritinib on the breastfed child or its effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with ZYKADIA and for 2 weeks following completion of therapy.
Females and Males of Reproductive Potential: Pregnancy Testing: Verify pregnancy status in females of reproductive potential prior to initiating ZYKADIA [see Pregnancy as previously mentioned].
Contraception: ZYKADIA can cause fetal harm when administered to a pregnant woman [see Pregnancy as previously mentioned].
Females: Advise females of reproductive potential to use effective contraception during treatment with ZYKADIA and for 6 months following completion of therapy.
Males: Based on the potential for genotoxicity, advise males with female partners of reproductive potential to use condoms during treatment with ZYKADIA and for 3 months following completion of therapy [see Pharmacology: Nonclinical Toxicology: Carcinogenesis, Mutagenesis, Impairment of Fertility under Actions].