forganogenesis. Maternal findings at 30 mg/kg/day (resulting in exposuresapproximately 0.4 times the AUC24 in patients receiving the recommended dose) included decreased body weight andfood consumption. Administration of gilteritinib at the dose of 30 mg/kg/day also resulted in embryo-fetal death(postimplantation loss), decreased fetal body and placental weight, and decreased numbers of ossified sternebrae andsacral and caudal vertebrae, and increased incidence of fetal gross external (anasarca, local edema, exencephaly, cleft lip,cleft palate, short tail, and umbilical hernia), visceral (microphthalmia; atrial and/or ventricular defects; andmalformed/absent kidney, and malpositioned adrenal, and ovary), and skeletal (sternoschisis, absent rib, fused rib, fusedcervical arch, misaligned cervical vertebra, and absent thoracic vertebra) abnormalities.
Single oral administration of [14C] gilteritinib to pregnant rats resulted in transfer of radioactivity to the fetus similar tothat observed in maternal plasma on day 14 of gestation. In addition, distribution profiles of radioactivity in most maternaltissues and the fetus on day 18 of gestation were similar to that on day 14 of gestation.
8.2 Lactation
Risk Summary
There are no data on the presence of gilteritinib and/or its metabolites in human milk, the effects on the breastfed child, orthe effects on milk production. Following administration of radiolabeled gilteritinib to lactating rats, milk concentrationsof radioactivity were higher than radioactivity in maternal plasma at 4 and 24 hours post-dose. In animal studies,gilteritinib and/or its metabolite(s) were distributed to the tissues in infant rats via the milk. Because of the potential forserious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment withXOSPATA and for 2 months after the last dose.
8.3 Females and Males of Reproductive Potential
Pregnancy testing
Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating XOSPATAtreatment [see Use in Specific Populations (8.1)].
Contraception
Females
Advise females of reproductive potential to use effective contraception during treatment and for at least 6 months after thelast dose of XOSPATA.
Males
Advise males of reproductive potential to use effective contraception during treatment and for at least 4 months after the
last dose of XOSPATA.
8.4 Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric Use
Of the 292 patients in clinical studies of XOSPATA, 41% were age 65 years or older, and 13% were 75 years or older. Nooverall differences in effectiveness or safety were observed between patients age 65 years or older and younger patients.
11 DESCRIPTION
Gilteritinib is a tyrosine kinase inhibitor. The chemical name is 2-Pyrazinecarboxamide, 6-ethyl-3-[[3-methoxy-4-[4-(4methyl-1-piperazinyl)-1-piperidinyl] phenyl] amino]-5-[(tetrahydro-2H-pyran-4-yl) amino]-, (2E)-2-butenedioate (2:1).
The molecular weight is 1221.50 and the molecular formula is (C29H44N8O3)2·C4H4O4. The structural formula is:Gilteritinib fumarate is a light yellow to yellow powder or crystals that is sparingly soluble in water and very slightlysoluble in anhydrous ethanol.
XOSPATA (gilteritinib) is provided as a tablet for oral administration. Each tablet contains 40 mg |
