Gilteritinib
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From MedlinePlus, U.S. National Library of Medicine
Specialty pharmacy: therapy management checklist, storage and cold chain, dosing calendar, Medicare Part D coverage.
Boxed warning
WARNING: DIFFERENTIATION SYNDROME Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal or life-threatening if not treated. Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . WARNING: DIFFERENTIATION SYNDROME See full prescribing information for complete boxed warning.
Patients treated with XOSPATA have experienced symptoms of differentiation syndrome, which can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution. ( 5.1 , 6.1 )
Dosing in kidney impairment
Symptoms and other clinical findings of differentiation syndrome in patients treated with XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis.
Drug interactions
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Add the patient's other drugs. Matches come from both FDA labels: by name, drug class, and enzyme or transporter pathway.
- Gilteritinib
Label text (5 paragraphs)
7 DRUG INTERACTIONS • Combined P-gp and Strong CYP3A Inducers: Avoid concomitant use. ( 7.1 ) • Strong CYP3A Inhibitors: Consider alternative therapies. If the concomitant use of strong CYP3A inhibitors cannot be avoided, monitor patients more frequently for XOSPATA adverse reactions. ( 2.3 , 7.1 ) • P-gp, BCRP, OCT1 Substrates: Decrease the dose of the substrates when coadministered with gilteritinib and as clinically indicated. ( 7.2 )
7.1 Effect of Other Drugs on XOSPATA Combined P-gp and Strong CYP3A Inducers Concomitant use of XOSPATA with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure which may decrease XOSPATA efficacy [see Clinical Pharmacology ( 12.3 )] . Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers. Strong CYP3A Inhibitors Concomitant use of XOSPATA with a strong CYP3A inhibitor increases gilteritinib exposure [see Clinical Pharmacology ( 12.3 )] . Consider alternative therapies that are not strong CYP3A inhibitors.
If the concomitant use of these inhibitors is considered essential for the care of the patient, monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in patients with serious or life-threatening toxicity [see Dosage and Administration ( 2.3 )] .
7.2 Effect of XOSPATA on Other Drugs Drugs that Target 5HT2B Receptor or Sigma Nonspecific Receptor Concomitant use of gilteritinib may reduce the effects of drugs that target the 5HT 2B receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant use of these drugs with XOSPATA unless their use is considered essential for the care of the patient [see Clinical Pharmacology ( 12.3 )] . P-gp, BCRP, and OCT1 Substrates Based on in vitro data, gilteritinib is a P-gp, breast cancer resistant protein (BCRP), and organic cation transporter 1 (OCT1) inhibitor.
Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates, which may increase the incidence and severity of adverse reactions of these substrates [see Clinical Pharmacology ( 12.3 )]. For P-gp, BCRP, or OCT1 substrates where small concentration changes may lead to serious adverse reactions, decrease the dose or modify the dosing frequency of such substrate and monitor for adverse reactions as recommended in the respective prescribing information.
Contraindications
4 CONTRAINDICATIONS XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials [see Adverse Reactions ( 6 ) and Description ( 11 )] . Hypersensitivity to gilteritinib or any of the excipients. Anaphylactic reactions have been observed in clinical trials. ( 4 , 6.1 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Unproved but suspected cause of clinically apparent liver injury.
Gilteritinib is an orally available small molecule inhibitor of FMS-like tyrosine kinase 3 (FLT3) which is used as an antineoplastic agent in the treatment of acute myeloid leukemia with FLT3 mutations. Gilteritinib is associated with a moderate rate of serum aminotransferase elevations during therapy and is suspected to cause rare instances of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 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 ( 12.1 )] . 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 (AUC 24 ) approximately 0.4 times the AUC 24 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 AUC 24 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 [ 14 C] 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.
Breastfeeding (LactMed)
No information is available on gilteritinib during breastfeeding. It is 94% bound to plasma proteins, so amounts in milk are likely to be low; however, it has a long half-life of about 113 hours. The manufacturer recommends that breastfeeding be discontinued during gilteritinib therapy and for 2 months after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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