Gilteritinib

Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.

• XOSPATA is a kinase inhibitor indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. ( 1.1 ) 1.1 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.ICD-10: C95.90

• 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 )] .contraindicated

120 mg orally once daily. ( 2.2 ) 2.1 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 ( 14 )]. Information on FDA-approved tests for the detection of a FLT3 mutation in AML is available at http://www.fda.gov/CompanionDiagnostics . 2.2 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. 2.3 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 .

• Posterior reversible encephalopathy syndrome (PRES): Discontinue XOSPATA in patients who develop PRES. ( 2.3 , 5.2 , 6.1 ) • Prolonged QT Interval: Interrupt and reduce XOSPATA dosage in patients who have a QTcF >500 msec. Correct hypokalemia or hypomagnesemia prior to and during XOSPATA administration. ( 2.3 , 5.3 , 12.2 , 6.1 ) • Pancreatitis: Interrupt and reduce the dose in patients who develop pancreatitis. ( 2.3 , 5.4 ) • Embryo-Fetal Toxicity: XOSPATA can cause fetal harm when administered to a pregnant woman. Advise of the potential risk to a fetus and to use effective contraception. ( 5.5 , 8.1 , 8.3 ) 5.1 Differentiation Syndrome Of 319 patients treated with XOSPATA in the clinical trials, 3% experienced differentiation syndrome. Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. 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. Differentiation syndrome occurred as early as 1 day and up to 82 days after XOSPATA initiation and has been observed with or without concomitant leukocytosis. Of the 11 patients who experienced differentiation syndrome, 9 (82%) recovered after treatment or after dose interruption of XOSPATA.

The following clinically significant adverse reactions are described elsewhere in the labeling: • Differentiation syndrome [see Boxed Warning and Warnings and Precautions ( 5.1 )] • Posterior reversible encephalopathy syndrome [see Warnings and Precautions ( 5.2 )] • Prolonged QT interval [see Warnings and Precautions ( 5.3 )] • Pancreatitis [see Warnings and Precautions ( 5.4 )] The most common adverse reactions (≥20%) are transaminase increased, myalgia/arthralgia, fatigue/malaise, fever, mucositis, edema, rash, noninfectious diarrhea, dyspnea, nausea, cough, constipation, eye disorders, headache, dizziness, hypotension, vomiting, and renal impairment. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Astellas Pharma US, Inc. at 1-800-727-7003 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety profile of XOSPATA is based on 319 patients with relapsed or refractory AML treated with gilteritinib 120 mg daily in three clinical trials. The median duration of exposure to XOSPATA was 3.6 months (range 0.1 to 43.4 months). Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These included cardiac arrest (1%) and one case each of differentiation syndrome and pancreatitis.

Lactation: Advise women not to breastfeed. ( 8.2 ) 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.

Metabolism

The following pharmacokinetic parameters were observed following administration of gilteritinib 120 mg once daily, unless otherwise specified. Gilteritinib exposure (C max and AUC 24 ) increases proportionally with once daily doses ranging from 20 mg to 450 mg (0.17 to 3.75 times the recommended dosage) in patients with relapsed or refractory AML.

• Nov 28, 2018NDANDA211349Astellas

1. 1Off Label Use45612%
2. 2Acute Myeloid Leukaemia3368.9%
3. 3Myelosuppression2787.3%
4. 4Platelet Count Decreased2747.2%
5. 5Pneumonia2657.0%
6. 6Death2606.9%
7. 7Pyrexia2496.6%
8. 8Febrile Neutropenia2356.2%
9. 9Product Use Issue2155.7%
10. 10Acute Myeloid Leukaemia Recurrent1694.5%
11. 11Cytopenia1544.1%
12. 12Infection1504.0%
13. 13Thrombocytopenia1493.9%
14. 14Drug Ineffective1433.8%
15. 15Neutropenia1323.5%

The 10 most recently updated of 77 ClinicalTrials.gov registrations naming Gilteritinib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
  Recruiting · Phase 2 · Interventional · 2,000 enrolled · National Cancer Institute (NCI)
  NCT05564390updated 2026-06-11
• ASTX727, Venetoclax, and Gilteritinib for the Treatment of Newly Diagnosed, Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
  Recruiting · Phase 1 · Phase 2 · Interventional · 42 enrolled · M.D. Anderson Cancer Center
  NCT05010122updated 2026-06-11
• Venetoclax and HMA Treatment of Older and Unfit Adults With FLT3 Mutated Acute Myeloid Leukemia (AML) (A MyeloMATCH Treatment Trial)
  Recruiting · Phase 2 · Interventional · 147 enrolled · National Cancer Institute (NCI)
  NCT06317649updated 2026-06-11
• IMPACT-AML: A Randomized Pragmatic Clinical Trial for Relapsed or Refractory Acute Myeloid Leukemia.
  Recruiting · Phase 3 · Interventional · 339 enrolled · Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS
  NCT06713837updated 2026-06-10
• A Phase I/II Study of Gilteritinib and Momelotinib for Patients With Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 20 enrolled · M.D. Anderson Cancer Center
  NCT06235801updated 2026-06-10
• A Study of Gilteritinib in Adults With Advanced ALK-positive Non-small Cell Lung Cancer (NSCLC)
  Recruiting · Phase 1 · Interventional · 40 enrolled · Astellas Pharma Global Development, Inc.
  NCT07140016updated 2026-06-08
• Study of SA+X in the Treatment of Newly Diagnosed AML
  Recruiting · Phase 2 · Interventional · 205 enrolled · Ruijin Hospital
  NCT07548710updated 2026-06-03
• Cladribine, Idarubicin, Cytarabine, and Venetoclax in Treating Patients With Acute Myeloid Leukemia, High-Risk Myelodysplastic Syndrome, or Blastic Phase Chronic Myeloid Leukemia
  Recruiting · Phase 2 · Interventional · 508 enrolled · M.D. Anderson Cancer Center
  NCT02115295updated 2026-05-20
• SNDX-5613 and Gilteritinib for the Treatment of Relapsed or Refractory FLT3-Mutated Acute Myeloid Leukemia and Concurrent MLL-Rearrangement or NPM1 Mutation
  Recruiting · Phase 1 · Interventional · 30 enrolled · Uma Borate
  NCT06222580updated 2026-05-14
• The Efficacy of Triple Regimen in Newly Diagnosed AML Patients With FLT3 Mutation
  Recruiting · Phase 1 · Phase 2 · Interventional · 66 enrolled · Institute of Hematology & Blood Diseases Hospital, China
  NCT06561880updated 2026-05-13

Frequently asked questions

How does Gilteritinib work?

Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3). Gilteritinib demonstrated the ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells expressing FLT3-ITD.

What is Gilteritinib used for?

According to FDA labeling, Gilteritinib carries indications including: XOSPATA is a kinase inhibitor indicated for the treatment of adult patients who have relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation as detected by an FDA-approved test. ( 1.1 ) 1.1 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.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Gilteritinib?

Gilteritinib is classified as Other protein kinase inhibitors, Receptor Tyrosine Kinase Inhibitors, Cellular Proliferation Alteration, Increased Cellular Death.

What are the brand names for Gilteritinib?

Gilteritinib is marketed under brand names including Xospata.

What are the contraindications for Gilteritinib?

Gilteritinib labeling lists contraindications including: 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 )] .. Always consult the full prescribing information and a clinician.