tion, the estimated background risk of major birth defects and miscarriage inclinically recognized pregnancies is 2-4% and 15-20%, respectively.
Data
Animal Data
In an embryo-fetal toxicity study, erdafitinib was orally administered to pregnant rats during the periodof organogenesis. Doses ≥4mg/kg/day (at total maternal exposures <0.1% of total human exposures atthe maximum recommended human dose based on AUC) produced embryo-fetal death, major bloodvessel malformations and other vascular anomalies, limb malformations (ectrodactyly, absent ormisshapen long bones), an increased incidence of skeletal anomalies in multiple bones (vertebrae,
sternebrae, ribs), and decreased fetal weight.
8.2 Lactation
Risk Summary
There are no data on the presence of erdafitinib in human milk, or the effects of erdafitinib on thebreastfed child, or on milk production. Because of the potential for serious adverse reactions fromerdafitinib in a breastfed child, advise lactating women not to breastfeed during treatment withBALVERSA and for one month following the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to initiating treatmentwith BALVERSA.
Contraception
Females
BALVERSA can cause fetal harm when administered to a pregnant woman. Advise females ofreproductive potential to use effective contraception during treatment with BALVERSA and for onemonth after the last dose [see Use in Specific Population (8.1)].
Males
Advise male patients with female partners of reproductive potential to use effective contraception duringtreatment with BALVERSA and for one month after the last dose [see Use in Specific Populations(8.1)].
Infertility
Females
Based on findings from animal studies, BALVERSA may impair fertility in females of reproductivepotential [see Nonclinical Toxicology (13.1)].
8.4 Pediatric Use
Safety and effectiveness of BALVERSA in pediatric patients have not been established.
In 4 and 13-week repeat-dose toxicology studies in rats and dogs, toxicities in bone and teeth wereobserved at an exposure less than the human exposure (AUC) at the maximum recommended humandose. Chondroid dysplasia/metaplasia were reported in multiple bones in both species, and toothabnormalities included abnormal/irregular denting in rats and dogs and discoloration and degenerationof odontoblasts in rats.
8.5 Geriatric Use
Of the 416 patients treated with BALVERSA in clinical studies, 45% were 65 years of age or older, and12% were 75 years of age or older. No overall differences in safety or effectiveness were observedbetween these patients and younger patients [see Clinical Studies (14)].
8.6 CYP2C9 Poor Metabolizers
CYP2C9*3/*3 Genotype: Erdafitinib plasma concentrations were predicted to be higher in patients withthe CYP2C9*3/*3 genotype. Monitor for increased adverse reactions in patients who are known orsuspected to have CYP2C9*3/*3 genotype [see Pharmacogenomics (12.5)].
11 DESCRIPTION
Erdafitinib, the active ingredient in BALVERSA, is a kinase inhibitor. The chemical name is N-(3,5dimethoxyphenyl)-N’-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2diamine. Erdafitinib is a yellow powder. It is practically insoluble, or insoluble to freely soluble inorganic solvents, and slightly soluble to practic |
