Gilteritinib (Xospata) — Clinical FAQs

Question 1

What is Gilteritinib FDA-approved to treat?

Accepted Answer

Gilteritinib is FDA-approved for the following oncology indications: 1. Relapsed or refractory acute myeloid leukemia (AML) with a FLT3 mutation (ITD or TKD) in adults — approved Nov 2018 (ADMIRAL trial).

Question 2

How does Gilteritinib work (mechanism of action)?

Accepted Answer

Gilteritinib is a potent, selective inhibitor of FLT3 (FMS-like tyrosine kinase 3) and AXL receptor tyrosine kinase. It inhibits both FLT3 internal tandem duplication (FLT3-ITD) and tyrosine kinase domain (FLT3-TKD) point mutations (D835, I836), overcoming a key resistance mechanism to first-generation FLT3 inhibitors. Inhibition of constitutively activated FLT3 signaling suppresses the RAS/MAPK, PI3K/AKT, and STAT5 pathways that drive leukemic proliferation and survival in FLT3-mutated AML. AXL inhibition may contribute additional antileukemic activity and potentially reduces resistance to FLT3 inhibition.

Question 3

How is Gilteritinib administered?

Accepted Answer

Gilteritinib is administered Oral (PO). Recommended dose: 120 mg PO once daily with or without food.

Question 4

What are the most common side effects of Gilteritinib?

Accepted Answer

The most commonly reported side effects of Gilteritinib (≥10% incidence) include: Fatigue/malaise (≥26%), Transaminase elevations (AST/ALT ≥20%), Febrile neutropenia, Nausea (~20%), Musculoskeletal pain and others (13 total). Consult your oncologist for complete prescribing information.

Question 5

Does Gilteritinib have a black box warning?

Accepted Answer

Yes. Gilteritinib carries FDA black box warning(s) regarding: 1. Differentiation syndrome: reported in patients treated with gilteritinib, including fatal cases. Symptoms include fever, dyspnea, hypoxia, pulmonary infiltrates, pericardial/pleural effusion, rapid weight gain, and peripheral edema. Treat with dexamethasone 10 mg IV every 12 hours and hemodynamic monitoring; interrupt gilteritinib if severe signs/symptoms persist >48 hours

Question 6

Is Gilteritinib safe during pregnancy?

Accepted Answer

Gilteritinib pregnancy safety: Based on animal reproductive studies and mechanism of action, gilteritinib can cause embryo-fetal harm. Female patients of reproductive potential should use effective contraception during treatment and for 6 months after the last dose; male patients should use contraception for 4 months after the last dose. Breastfeeding should be discontinued during therapy.. Oncologists should review the complete prescribing information and discuss reproductive risks with patients before initiating therapy.

gilteritinib — Drug Monograph

Mechanism of Action

FDA Indications

Common Side Effects

Clinical Pearl

Related Therapies & Mechanisms