Gilteritinib, an inhibitor of multiple receptor tyrosine kinases, including fms-like tyrosine kinase-3 (Flt-3), is an antineoplastic agent.1, 3
Gilteritinib fumarate is used for the treatment of relapsed or refractory acute myeloid leukemia (AML) harboring a fms-like tyrosine kinase-3 (Flt-3) mutation in adults.1, 3 Gilteritinib has been designated an orphan drug by the Food and Drug Administration (FDA) for the treatment of this cancer.2 An FDA-approved companion diagnostic test (e.g., LeukoStrat® CDx Flt-3 mutation assay) is required to confirm the presence of the Flt-3 mutation (peripheral blood or bone marrow) prior to initiation of therapy.1 The current indication is based on complete remission (CR) or complete remission with partial hematologic recovery (CRh) and improvement of hematologic deficits (determined by rate of conversion from transfusion dependence to transfusion independence).1, 5 Safety and efficacy of gilteritinib in this use is based principally on the results of a phase 3, open-label, controlled trial in adults with relapsed or refractory AML with an internal tandem duplication (ITD) or a point mutation in the tyrosine kinase domain (TKD) of Flt-3 kinase.1, 3, 5, 12, 13 The National Cancer Institute states there is no standard treatment regimen for relapsed or refractory AML; patients who are unable or unwilling to undergo intensive therapy may be candidates for reduced-intensity therapies, including gilteritinib.15
The current indication for gilteritinib in the treatment of AML is based principally on the results of a planned interim and final analysis of the open-label, controlled phase 3 study (ADMIRAL) in adults with relapsed or refractory AML with an ITD or a point mutation in the TKD of Flt-3 kinase as detected by the LeukoStrat® CDx Flt-3 mutation assay.1, 3, 5 The primary measures of efficacy were CR and CRh, duration of response, and loss of transfusion dependence (red blood cells [RBCs] and/or platelets).1 CR was defined as the presence of <5% blasts in bone marrow without evidence of extramedullary disease or myeloid differentiation, full recovery of peripheral blood cell counts (absolute neutrophil count [ANC] ≥1000/mm3, platelet count ≥100,000/mm3), and transfusion independence.1 Complete remission with partial hematologic recovery was defined as the presence of <5% blasts in bone marrow without evidence of extramedullary disease and with incomplete recovery of peripheral blood cell counts (ANC ≥500/mm3, platelet count ≥50,000/mm3).1
In this study, 371 adults were randomized in a 2:1 ratio to receive either gilteritinib (initial dosage of 120 mg once daily; dosage escalations up to 200 mg once daily were permitted) or a preselected salvage chemotherapy regimen (cytarabine 20 mg IV or subcutaneously twice daily for 10 days; azacitidine 75 mg/m2 IV or subcutaneously daily for 7 days; mitoxantrone 8 mg/m2 IV daily for 5 days in combination with etoposide 100 mg/m2 IV daily for 5 days and cytarabine 1 g/m2 IV daily for 5 days [MEC]; fludarabine phosphate 30 mg/m2 IV daily for 5 days, cytarabine 2 g/m2 IV daily for 5 days, and idarubicin hydrochloride 10 mg/m2 IV daily for 3 days with granulocyte colony-stimulating factor [G-CSF] 300 mcg/m2 IV daily for 5 days [FLAG-IDA]).1, 2, 3, 5, 11 Gilteritinib therapy was continued until disease progression or unacceptable toxicity occurred.1 Allogeneic stem cell transplantation was permitted in patients who achieved CR.1
The median age of patients randomized to receive gilteritinib was 60 years (range: 20-84 years); 56% were Caucasian,5 38% were ≥65 years of age, 46% were male, 82% had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, 59% had previously untreated relapsed AML, 41% had primary refractory AML, 77% were transfusion dependent at baseline, and 20% had previously undergone stem cell transplantation.1 Flt-3-ITD mutations were present in 88% of patients and Flt-3-TKD (D835 or I836) mutations were present in 9% of patients.1
At a median follow-up of 4.6 months, CR or CRh was achieved in 21% of gilteritinib-treated patients with a median response duration of 4.6 months; 11.6% of patients achieved CR.1 The median time to initial CR or CRh in gilteritinib-treated patients was 3.6 months.1 Approximately one-third (31%) of gilteritinib-treated patients who were transfusion dependent at baseline became transfusion independent during any 56-day period during the study.1 The majority (53%) of gilteritinib-treated patients who were transfusion independent at baseline remained transfusion independent during any 56-day period during the study.1
The final analysis of the ADMIRAL trial included 371 patients randomized to gilteritinib (n=247) or chemotherapy (n=124).1, 12 Patient characteristics were similar to those in the interim analysis.1 After a median follow-up of 17.8 months, overall survival was substantially longer among patients treated with gilteritinib compared with chemotherapy (median, 9.3 versus 5.6 months, respectively; hazard ratio, 0.64; 95% CI, 0.49-0.83).1, 12 In the final analysis, the CR/CRh rate in patients treated with gilteritinib was 22.6% and the duration of response was 7.4 months.1 Among patients treated with gilteritinib who were transfusion-dependent at baseline, 34.5% became transfusion-independent during any 56-day post-baseline period. Among patients who were transfusion-independent at baseline, 59.2% remained transfusion-independent during any 56-day post-baseline period.1 A follow-up study of the ADMIRAL trial 2 years after the primary analysis found that, after a median survival follow-up of 37.1 months, maintenance treatment with gilteritinib was associated with sustained efficacy and safety.13
The National Cancer Institute (NCI) states that there is no standard treatment regimen for patients with refractory or recurrent AML.15 Treatment options may include chemotherapy (intensive salvage chemotherapy and reduced-intensity therapy, including targeted therapy) and allogeneic hematopoietic cell transplantation (HCT).15
Intensive salvage chemotherapy may use a number of regimens, including fludarabine, cytarabine, and filgrastim (FLAG); mitoxantrone, etoposide, and cytarabine (MEC); standard or high-dose cytarabine and mitoxantrone; high-dose etoposide and cyclophosphamide; idarubicin and cytarabine; and other intensive regimens.15 Patients who are unable or unwilling to undergo intensive therapy may be candidates for reduced-intensity therapies such as gilteritinib, enasidenib, or ivosidenib, depending on the presence of specific mutations; hypomethylating agents, gemtuzumab ozogamicin, and clofarabine with or without cytarabine are also options.15 Allogeneic HCT may be an option in patients who have not experienced remission with intensive chemotherapy.15
Dispensing and Administration Precautions
Gilteritinib fumarate is administered orally once daily without regard to meals.1 The drug should be taken at approximately the same time each day.1 The tablets should be swallowed whole with a cup of water; they should not be chewed, crushed, or broken.1
If a dose of gilteritinib is missed by 12 hours or less, administer the missed dose on the same day as soon as it is remembered and take the next dose at the regularly scheduled time on the following day.1 If a dose of gilteritinib is missed by more than 12 hours, administer the next dose at the regularly scheduled time; do not administer an additional dose to replace the missed dose.1 Advise patients not to take 2 doses within a 12-hour period.1
Intact gilteritinib tablets can be handled without gloves; however, if the tablets are accidentally broken or crushed, chemically resistant protective gloves should be worn.14
Store gilteritinib at 20-25°C (excursions permitted between 15-30°C).1 Store in original container.1 Protect from light, moisture, and humidity.1
Dosage of gilteritinib fumarate is expressed in terms of gilteritinib.1
For the treatment of relapsed or refractory AML with Flt-3 mutation, the recommended initial adult dosage of gilteritinib is 120 mg once daily.1, 3 Therapy should be continued for at least 6 months to allow time for response or until disease progression or unacceptable toxicity occurs.1
Dosage Modification for Toxicity
If differentiation syndrome is suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptoms resolve and for a minimum of 3 days.1
Interrrupt treatment with gilteritinib if severe signs and/or symptoms continue for more than 48 hours after initiation of corticosteroids.1
Resume gilteritinib when signs and symptoms improve to grade 2 (i.e., moderate) or lower.1
Posterior Reversible Encephalopathy Syndrome
If posterior reversible encephalopathy syndrome occurs, gilteritinib therapy should be discontinued.1
If the corrected QT (QTc) interval exceeds 500 msec, gilteritinib should be withheld.1 When the QTc interval improves to 480 msec or less or no more than 30 msec from baseline, gilteritinib may be resumed at a reduced dosage of 80 mg daily.1
If the QTc interval increases by more than 30 msec from baseline on day 8 of cycle 1, confirm with an ECG on day 9.1 If QTc interval increase is confirmed on day 9, consider dosage reduction of gilteritinib to 80 mg daily.1
If pancreatitis occurs, gilteritinib therapy should be withheld.1 Upon resolution of pancreatitis, gilteritinib may be resumed at a reduced dosage of 80 mg daily.1
If other grade 3 or 4 adverse reaction occurs, therapy with gilteritinib should be withheld.1 When the toxicity improves to grade 1 or less, gilteritinib may be resumed at a reduced dosage of 80 mg daily.1
The manufacturer makes no specific dosage recommendations for patients with hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with renal impairment.1
The manufacturer makes no specific dosage recommendations for geriatric patients.1
Gilteritinib fumarate is contraindicated in patients with hypersensitivity to the drug or any ingredient in the formulation.1
The prescribing information of gilteritinib contains a boxed warning regarding the risk of differentiation syndrome, which can be fatal or life-threatening if untreated.1 Differentiation syndrome is associated with rapid proliferation and differentiation of myeloid cells and may occur as early as day 1 and up to 82 days after gilteritinib initiation.1 In clinical trials, 3% of patients experienced differentiation syndrome. Of these, 82% recovered after treatment or dose interruption of gilteritinib.1
Symptoms of differentiation syndrome and clinical findings may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, rash, or renal dysfunction.1 If differentiation syndrome is suspected, initiate corticosteroid therapy with dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until symptom resolution.1 Following symptom resolution, taper corticosteroids and administer corticosteroids for a minimum of 3 days.1 Symptoms of differentiation syndrome may recur if corticosteroid treatment is prematurely discontinued.1 If severe signs and/or symptoms continue for more than 48 hours after corticosteroid initiation, interrupt gilteritinib until signs and symptoms are no longer severe.1
Posterior Reversible Encephalopathy Syndrome
Posterior reversible encephalopathy syndrome has been reported rarely in patients receiving gilteritinib.1 In clinical trials, this syndrome occurred in 1% of patients receiving gilteritinib.1 Manifestations include seizure and altered mental status, which may resolve upon discontinuance of the drug.1 Brain imaging, preferably magnetic resonance imaging (MRI), is used to confirm the diagnosis.1 Gilteritinib therapy should be discontinued in patients who develop posterior reversible encepalopathy syndrome.1
Prolongation of the corrected QT (QTc) interval has been observed in patients receiving gilteritinib.1 In clinical trials, an increase in the QTc interval exceeding 60 msec from baseline occurred in 7% of gilteritinib-treated patients, and QTc intervals exceeding 500 msec occurred in 1% of gilteritinib-treated patients.1
Electrocardiograms should be assessed prior to initiation of gilteritinib, on days 8 and 15 of cycle 1, and prior to initiation of cycles 2 and 3.1 In addition, serum electrolytes (e.g., potassium, magnesium) should be assessed prior to initiation of gilteritinib therapy and monitored at least weekly for the first month of therapy, every other week for the following month of therapy, and then monthly thereafter.1 Because of the increased risk of QT interval prolongation in patients with hypokalemia and hypomagnesemia, such electrolyte abnormalities should be corrected prior to initiation of and during gilteritinib therapy.1 Temporary interruption and/or dosage reduction may be necessary in patients who experience prolongation of the QTc interval during therapy with the drug.1
Pancreatitis was reported in 4% of patients receiving gilteritinib in clinical trials.1 Patients presenting with manifestations of pancreatitis (e.g., severe and persistent abdominal pain, which may be accompanied by nausea or vomiting) should be evaluated.1 Temporary interruption followed by dosage reduction may be necessary in patients who develop pancreatitis.1
Fetal/Neonatal Morbidity and Mortality
Gilteritinib may cause fetal harm in humans based on its mechanism of action and animal findings; the drug has been shown to be embryotoxic, fetotoxic, and teratogenic in animals.1 There are no available data regarding the risk of gilteritinib use in pregnant women to date to inform a drug-associated risk of adverse developmental outcomes.1 In animal reproduction studies, embryofetal toxicity (i.e., postimplantation loss, decreases in fetal body and placental weight) and teratogenic effects (i.e., gross external, visceral, and skeletal anomalies) were observed in rats receiving gilteritinib at exposure levels approximately 0.4 times the human exposure at the recommended dosage.1
Placental transfer of gilteritinib has been observed in rats.1, 5 Following administration of a radiolabeled dose of gilteritinib on gestation day 14, radioactivity of the drug in the fetus was similar to radioactivity of the drug observed in maternal plasma.1, 5
Pregnancy should be avoided during gilteritinib therapy.1 The manufacturer recommends confirmation of pregnancy status within 7 days prior to initiation of gilteritinib in females of reproductive potential and states that such patients should be advised to use effective contraceptive methods while receiving gilteritinib and for at least 6 months after discontinuance of the drug.1 In addition, male patients with such female partners should use effective methods of contraception while receiving gilteritinib and for at least 4 months after discontinuance of the drug.1 Patients should be apprised of the potential hazard to the fetus if gilteritinib is used during pregnancy.1
Gilteritinib may cause fetal harm if administered to pregnant females based on its mechanism of action and animal findings.1
The manufacturer recommends confirmation of pregnancy status in females of reproductive potential within 7 days prior to initiation of gilteritinib therapy.1
Gilteritinib and/or its metabolite(s) are distributed into milk in rats.1, 5 It is not known whether the drug or its metabolites distribute into human milk or if the drug has any effect on milk production or the nursing infant.1 Low amounts of gilteritinib are expected to distribute into human milk since the drug is highly bound to plasma proteins; however, the drug has a long half-life of 113 hours.6 Because of the potential for serious adverse reactions to gilteritinib in nursing infants, patients should be advised to discontinue nursing during gilteritinib therapy and for at least 2 months after discontinuance of therapy.1, 6
Females and Males of Reproductive Potential
The effect of gilteritinib on fertility in humans is not known.1 Based on animal studies, gilteritinib may impair male fertility.1 In male dogs, gilteritinib was associated with degeneration and necrosis of germ cells, formation of spermatid giant cells, and single cell necrosis of the epididymal duct epithelia of the epididymal head.1, 5
Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose of gilteritinib.1 Advise males of reproductive potential to use effective contraception during treatment and for 4 months after the last dose of gilteritinib.1
Safety and efficacy of gilteritinib have not been established in pediatric patients.1
In clinical trials evaluating gilteritinib in patients with relapsed or refractory acute myeloid leukemia (AML), 43% of patients receiving gilteritinib were 65 years of age or older, while 13% were 75 years of age or older.1 No overall differences in safety and efficacy were observed between geriatric patients and younger adults.1
In a hepatic impairment study, systemic exposure of unbound gilteritinib in noncancer patients with mild or moderate hepatic impairment (Child-Pugh class A or B) was similar to that in individuals with normal hepatic function.1, 5 The effects of severe hepatic impairment (Child-Pugh class C) on the pharmacokinetics of gilteritinib have not been established.1
Formal pharmacokinetic studies of gilteritinib have not been conducted in patients with renal impairment; however, gilteritinib undergoes minimal renal elimination.5
In a population pharmacokinetic analysis, alterations in serum creatinine concentrations did not have a substantial effect on the systemic exposure of gilteritinib in patients with relapsed or refractory AML; therefore, mild or moderate renal impairment (creatinine clearance of 30-80 mL/minute) is not expected to have clinically important effects on the systemic exposure of gilteritinib.1, 5 The effects of severe renal impairment (creatinine clearance of 29 mL/minute or less) on the pharmacokinetics of gilteritinib have not been established.1
Adverse effects occurring in 20% or more of patients with relapsed or refractory AML receiving gilteritinib include increased transaminase, myalgia/arthralgia, fatigue/malaise, fever, mucositis, edema, rash, noninfectious diarrhea, dyspnea, nausea, cough, constipation, eye disorders, headache, dizziness, hypotension, vomiting, and renal impairment.1
Gilteritinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4.1 In vitro studies indicate that gilteritinib is a weak inhibitor of CYP3A4.5
In vitro, gilteritinib is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP).1 In vitro studies indicate that gilteritinib is a potent inhibitor of multidrug and toxin extrusion (MATE) transporter 1 and organic cation transporter (OCT) 25 and inhibits BCRP, P-gp, and OCT 1 at clinically relevant concentrations.1
Drugs Affecting Hepatic Microsomal Enzymes and/or Efflux Transport Systems
Concomitant use of gilteritinib with potent inhibitors of CYP3A may result in increased systemic exposure to gilteritinib.1 When the potent CYP3A4 and P-gp inhibitor itraconazole (200 mg twice daily on day 1 followed by 200 mg once daily on days 2-28) was administered concomitantly with gilteritinib (single 10-mg dose on day 6) in healthy individuals, peak plasma concentrations and area under the serum concentration-time curve (AUC) of gilteritinib were increased by approximately 20 and 120%, respectively.1, 5 When the moderate CYP3A4 inhibitor fluconazole (400 mg on day 1 followed by 200 mg once daily on days 2-28) was administered concomitantly with gilteritinib (single 10-mg dose on day 6) in healthy individuals, peak plasma concentrations and AUC of gilteritinib were increased by approximately 16 and 40%, respectively.1, 5
Concomitant use of gilteritinib with potent inhibitors of CYP3A (e.g., itraconazole) should be avoided, and selection of an alternative drug with less CYP3A inhibition potential should be considered.1 If concomitant use of a potent CYP3A inhibitor cannot be avoided, patients should be monitored more frequently for signs of gilteritinib toxicity.1 If serious or life-threatening toxicity occurs, temporary interruption of gilteritinib therapy followed by dosage reduction may be necessary.1
Inducers of CYP3A and Efflux Transport Systems
Concomitant use of gilteritinib with drugs that are combined P-gp and potent CYP3A inducers may result in decreased systemic exposure to gilteritinib and reduced gilteritinib efficacy.1 When the P-gp and potent CYP3A4 inducer rifampin (600 mg once daily for 21 days) was administered concomitantly with gilteritinib (single 20-mg dose on day 8) in healthy individuals, peak plasma concentrations and AUC of gilteritinib were decreased by approximately 30 and 70%, respectively.1, 5
Concomitant use of gilteritinib with drugs that are combined P-gp and potent CYP3A inducers (e.g., rifampin) should be avoided.1
Drugs Metabolized by Hepatic Microsomal Enzymes
When gilteritinib was administered concomitantly with the CYP3A substrate midazolam (single 2-mg dose on day 15) in patients with relapsed or refractory acute myeloid leukemia (AML), peak plasma concentrations and AUC of midazolam were increased by approximately 10%.1, 5
Drugs Affected by Multidrug and Toxin Extrusion Transporter
When gilteritinib (200 mg once daily) was administered concomitantly with the MATE1 substrate cephalexin (single 500-mg dose on day 15) in patients with relapsed or refractory AML, peak plasma concentrations and AUC of cephalexin were decreased by less than 10%.1, 5
Drugs that Interact with Serotonin Type 2B Receptor or Nonspecific -receptors
In vitro, gilteritinib is an inhibitor of type 2B serotonergic receptors (5-HT2B) and nonspecific σ-receptors.1 Concomitant use of gilteritinib with drugs that bind to 5-HT2B or nonspecific σ-receptors (e.g., escitalopram, fluoxetine, sertraline) may result in reduced efficacy of such drugs.1 Concomitant use of gilteritinib with drugs that bind to 5-HT2B or nonspecific σ-receptors should be avoided unless use of the drugs that interact with 5-HT2B or nonspecific σ-receptors is considered necessary.1
Substrates of P-gp, BCRP, and OCT1
Coadministration of gilteritinib may increase the exposure of P-gp, BCRP, and OCT1 substrates.1 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 the substrate and monitor for adverse reactions as recommended in the respective prescribing information.1
Gilteritinib, an inhibitor of multiple receptor tyrosine kinases including fms-like tyrosine kinase-3 (Flt-3), is an antineoplastic agent.1, 3 Receptor tyrosine kinases are involved in the initiation of various cascades of intracellular signaling events that lead to cell proliferation and/or influence processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis, inhibition of apoptosis), based on the respective kinase.8, 9 Gilteritinib has been shown to inhibit Flt-3 signaling resulting in inhibition of cell proliferation induced by Flt-3 mutations (i.e., internal tandem duplications [ITD] and/or tyrosine kinase domain [TKD] point mutations in codon D835Y).1, 3, 5 The drug also has demonstrated apoptosis in leukemic cells harboring Flt-3-ITD mutations in the presence or absence of Flt-3-TKD point mutations.1, 5 In vitro, gilteritinib has demonstrated potent inhibitory activity against AXL, an oncogenic tyrosine kinase commonly overexpressed in patients with acute myeloid leukemia (AML).3, 7 AXL promotes Flt-3 signaling and may contribute to the development of resistance to receptor tyrosine kinase inhibitors;3, 7 therefore, inhibitory activity against AXL may counteract a mechanism of resistance to the drug.3 The drug also has demonstrated inhibition of wild-type Flt-3, anaplastic lymphoma kinase (ALK), leukocyte receptor tyrosine kinase (LTK), and stem cell factor receptor (c-Kit).3, 7 In patients with relapsed or refractory AML receiving gilteritinib 120 mg daily, greater than 90% inhibition of Flt-3 phosphorylation occurred within 24 hours of the initial dose.1 Inhibition above 90% also has been demonstrated on day 8 of cycle 1 in patients with relapsed or refractory AML receiving a gilteritinib dosage of at least 80 mg daily.1, 5, 10
Peak plasma concentrations and area under the serum concentration-time curve (AUC) of gilteritinib are dose proportional over the gilteritinib dosage range of 20-450 mg daily in patients with relapsed or refractory AML.1, 7, 10 Following oral administration in a fasted state, the median time to peak plasma concentrations of gilteritinib is 4-6 hours.1, 7 Steady-state concentrations of gilteritinib are reached within 15 days of once-daily dosing and the accumulation ratio is approximately tenfold.1, 7, 10 Administration of a single 40-mg dose of gilteritinib with a high-fat, high-calorie meal (800-1000 calories with 500-600 calories from fat) decreased peak plasma concentrations and AUC of gilteritinib by 26 and less than 10%, respectively, compared with administration in the fasted state.1 Following oral administration with a high-fat meal, the median time to peak plasma concentrations of gilteritinib was delayed by 2 hours.1
Gilteritinib is metabolized principally by cytochrome P-450 (CYP) isoenzyme 3A4, via N -dealkylation and oxidation to the metabolites M17, M16, and M10; however, pharmacologic activity of these metabolites has not been established.1, 5 The metabolites M17, M16, and M10 account for 10% or less of the total drug exposure.1, 5 Gilteritinib is extensively distributed to tissues.1 Gilteritinib is highly bound (approximately 94%) to plasma proteins in vivo.1, 6 In vitro, the drug is primarily bound to albumin.1 The estimated half-life of gilteritinib is 113 hours.1, 6, 7 Following administration of a radiolabeled dose of gilteritinib, 64.5% of the recovered dose is excreted in feces and 16.4% is eliminated in urine (10% or less as unchanged drug).1, 5
The pharmacokinetics of gilteritinib do not appear to be affected by age (20-87 years), gender, or ethnicity (Japanese versus non-Japanese).1, 7
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Gilteritinib fumarate can only be obtained through designated specialty pharmacies and distributors.4 Clinicians may contact the manufacturer (Astellas) at 844-632-9272 or consult the Xospata® website (4 [Web]) for specific ordering and availability information.4
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Tablets, film-coated | 40 mg (of gilteritinib) | Xospata® | Astellas |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions August 28, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Astellas Pharma US, Inc. Xospata® (gilteritinib) tablets prescribing information. Northbrook, IL; 2022 Jan.
2. Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. Accessed 2022 Sep 15. [Web]
3. Gorcea CM, Burthem J, Tholouli E. ASP2215 in the treatment of relapsed/refractory acute myeloid leukemia with FLT3 mutation: background and design of the ADMIRAL trial. Future Oncol . 2018; 14:1995-2004. [PubMed 29498296]
4. Astellas Pharma US, Inc. Xospata® Support Solutions overview. From Xospata® for healthcare professionals website. Undated. Accessed 2022 Sep 15. [Web]
5. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 211349Orig1s000: Multi-discipline review. From FDA website. [Web]
6. Gilteritinib. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Updated 2018 Dec 3. Accessed 2022 Sep 15.
7. Usuki K, Sakura T, Kobayashi Y et al. Clinical profile of gilteritinib in Japanese patients with relapsed/refractory acute myeloid leukemia: An open-label phase 1 study. Cancer Sci . 2018; 109:3235-3244. [PubMed 30039554]
8. Escudier B, Gore M. Axitinib for the management of metastatic renal cell carcinoma. Drugs R D . 2011; 11:113-26. [PubMed 21679004]
9. Hu-Lowe DD, Zou HY, Grazzini ML et al. Nonclinical antiangiogenesis and antitumor activities of axitinib (AG-013736), an oral, potent, and selective inhibitor of vascular endothelial growth factor receptor tyrosine kinases 1, 2, 3. Clin Cancer Res . 2008; 14:7272-83. [PubMed 19010843]
10. Perl AE, Altman JK, Cortes J et al. Selective inhibition of FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1-2 study. Lancet Oncol . 2017; 18:1061-1075. [PubMed 28645776]
11. A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation. From clinicaltrials.gov registry. Accessed 2019 Mar 13. [Web]
12. Perl AE, Martinelli G, Cortes JE, et al. Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML. N Engl J Med. 2019;381(18):1728-1740.
13. Perl AE, Larson RA, Podoltsev NA, et al. Follow-up of patients with R/R FLT3-mutation-positive AML treated with gilteritinib in the phase 3 ADMIRAL trial. Blood. 2022;139(23):3366-3375.
14. Astellas. Northbrook, IL: Personal communication.
15. National Cancer Institute. Acute Myeloid Leukemia Treatment (PDQ®)-Health Professional Version. National Cancer Institute. Updated June 10, 2022. Accessed July 18, 2022. [Web]
16. Institute for Safe Medication Practices. ISMP list of high-alert medications in acute care settings. [Web]. Accessed 2023, Aug 23.