Xospata

Relapsed or Refractory Acute Myeloid Leukemia

XOSPATA is indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation as detected by an FDA-approved test.

Patient Selection

Select patients for the treatment of AML with XOSPATA based on the presence of FLT3 mutations in the blood or bone marrow [see Clinical Studies ]. Information on FDA-approved tests for the detection of a FLT3 mutation in AML is available at http://www.fda.gov/CompanionDiagnostics.

Recommended Dosage

The recommended starting dose of XOSPATA is 120 mg orally once daily with or without food. Response may be delayed. In the absence of disease progression or unacceptable toxicity, treatment for a minimum of 6 months is recommended to allow time for a clinical response.

Do not break or crush XOSPATA tablets. Administer XOSPATA tablets orally about the same time each day. If a dose of XOSPATA is missed or not taken at the usual time, administer the dose as soon as possible on the same day, and at least 12 hours prior to the next scheduled dose. Return to the normal schedule the following day. Do not administer 2 doses within 12 hours.

Dosage Modifications

Assess blood counts and blood chemistries, including creatine phosphokinase, prior to the initiation of XOSPATA, at least once weekly for the first month, once every other week for the second month, and once monthly for the duration of therapy. Perform electrocardiogram (ECG) prior to initiation of treatment with gilteritinib, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles.

Interrupt dosing or reduce dose for toxicities as per Table 1.

Pregnancy

Risk Summary

Based on findings from animal studies (see Data) and its mechanism of action, XOSPATA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ].

There are no available data on XOSPATA use in pregnant women to inform a drug-associated risk of adverse developmental outcomes. In animal reproduction studies, administration of gilteritinib to pregnant rats during organogenesis caused adverse developmental outcomes including embryo-fetal lethality, suppressed fetal growth, and teratogenicity at maternal exposures (AUC24) approximately 0.4 times the AUC24 in patients receiving the recommended dose (see Data). Advise pregnant women of the potential risk to a fetus.

Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Data

Animal Data

In an embryo-fetal development study in rats, pregnant animals received oral doses of gilteritinib of 0, 0.3, 3, 10, and 30 mg/kg/day during the period of organogenesis. Maternal findings at 30 mg/kg/day (resulting in exposures approximately 0.4 times the AUC24 in patients receiving the recommended dose) included decreased body weight and food 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 and sacral 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; and malformed/absent kidney, and malpositioned adrenal, and ovary), and skeletal (sternoschisis, absent rib, fused rib, fused cervical 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 to that observed in maternal plasma on day 14 of gestation. In addition, distribution profiles of radioactivity in most maternal tissues and the fetus on day 18 of gestation were similar to that on day 14 of gestation.

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, or the effects on milk production. Following administration of radiolabeled gilteritinib to lactating rats, milk concentrations of 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 for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during treatment with XOSPATA and for 2 months after the last dose.

Females and Males of Reproductive Potential

XOSPATA can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ].

Pregnancy testing

Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating XOSPATA treatment [see Use in Specific Populations ].

Contraception

Females

Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of XOSPATA.

Males

Advise males of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of XOSPATA.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

Of the 319 patients in clinical studies of XOSPATA, 43% were age 65 years or older, and 13% were 75 years or older. No overall differences in effectiveness or safety were observed between patients age 65 years or older and younger patients.