Xospata

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 



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This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xospata 40 mg film-coated tablets 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
Each film-coated tablet contains 40 mg gilteritinib (as fumarate)  
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Film-coated tablet. 
 
Round, light yellow film-coated tablet, debossed with the company logo and ‘235’ on the same side.  
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Xospata is indicated as monotherapy for the treatment of adult patients who have relapsed or 
refractory acute myeloid leukaemia (AML) with a FLT3 mutation (see sections 4.2 and 5.1).  
 
4.2 Posology and method of administration 
 
Treatment with Xospata should be initiated and supervised by a physician experienced in the use of 
anti-cancer therapies.  
 
Before taking gilteritinib, relapsed or refractory AML patients must have confirmation of FMS-like 
tyrosine kinase 3 (FLT3) mutation (internal tandem duplication [ITD] or tyrosine kinase domain 
[TKD]) using a validated test. 
 
Xospata may be re-initiated in patients following haematopoietic stem cell transplantation (HSCT) 
(see Table 1). 
 
Posology 
 
The recommended starting dose is 120 mg gilteritinib (three 40 mg tablets) once daily. 
 
Blood chemistries, including creatine phosphokinase, should be assessed prior to initiation of 
treatment, on day 15 and monthly for the duration of treatment.  
 
An electrocardiogram (ECG) should be performed before initiation of gilteritinib treatment, on day 8 
and 15 of cycle 1 and prior to the start of the next three subsequent months of treatment (see sections 
4.4 and 4.8).  
 
Treatment should continue until the patient is no longer clinically benefiting from Xospata or until 
unacceptable toxicity occurs. Response may be delayed; therefore, continuation of treatment at the 
prescribed dose for up to 6 months should be considered to allow time for a clinical response. 



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In the absence of a response (patient did not achieve a CRc) after 4 weeks of treatment, the dose can 
be increased to 200 mg (five 40 mg tablets) once daily, if tolerated or clinically warranted. 
 
Dose modifications 
 
Table 1. Xospata dose interruption, reduction and discontinuation recommendations in 
patients with relapsed or refractory AML 
Criteria Xospata dosing 
Symptoms of differentiation syndrome • If differentiation syndrome is suspected, 

administer corticosteroids and initiate 
hemodynamic monitoring (see section 4.4).  

• Interrupt gilteritinib if severe signs and/or 
symptoms persist for more than 48 hours 
after initiation of corticosteroids.  

• Resume gilteritinib at the same dose when 
signs and symptoms improve to Grade 2a or 
lower. 

Symptoms of posterior reversible 
encephalopathy syndrome 

• Discontinue gilteritinib. 

QTc interval >500 msec • Interrupt gilteritinib.  
• Resume gilteritinib at a reduced dose (80 mg 

or 120 mgb) when QTc interval returns to 
within 30 msec of baseline or ≤ 480 msec. 

QTc interval increased by >30 msec on 
ECG on day 8 of cycle 1 

• Confirm with ECG on day 9. 
• If confirmed, consider dose reduction to 

80 mg or 120 mgb. 
Symptoms of pancreatitis • Interrupt gilteritinib until pancreatitis is 

resolved.  
• Resume treatment with gilteritinib at a 

reduced dose (80 mg or 120 mgb). 
Other Grade 3a or higher toxicity 
considered related to treatment. 

• Interrupt gilteritinib until toxicity resolves or 
improves to Grade 1a.  

• Resume treatment with gilteritinib at a 
reduced dose (80 mg or 120 mgb). 

Planned HSCT • Interrupt treatment with gilteritinib one week 
prior to administration of the conditioning 
regimen for HSCT.  

• Treatment can be resumed 30 days after 
HSCT if engraftment was successful, the 
patient did not have grade ≥2 acute graft 
versus host disease and was in CRc.c  

a. Grade 1 is mild, Grade 2 is moderate, Grade 3 is serious, Grade 4 is life-threatening. 
b. The daily dose can be reduced from 120 mg to 80 mg or from 200 mg to 120 mg. 
c. Composite complete remission (CRc) is defined as the remission rate of all CR (see section 5.1 

for definition of CR), CRp [achieved CR except for incomplete platelet recovery (<100 x 
109/L)] and CRi (achieved all criteria for CR except for incomplete haematological recovery 
with residual neutropenia <1 x 109/L with or without complete platelet recovery). 

 
Xospata should be administered at about the same time each day. If a dose is missed or not taken at the 
usual time, the dose should be administered as soon as possible on the same day, and patients should 
return to the normal schedule the following day. If vomiting occurs after dosing, patients should not 
take another dose but should return to the normal schedule the following day. 
 
Elderly  
No dose adjustment is required in patients ≥65 years of age (see section 5.2). 



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Hepatic impairment 
No dose adjustment is required for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh 
Class B) hepatic impairment. Xospata is not recommended for use in patients with severe (Child-Pugh 
Class C) hepatic impairment, as safety and efficacy have not been evaluated in this population (see 
section 5.2). 
 
Renal impairment 
No dose adjustment is necessary in patients with mild or moderate renal impairment. There is no 
clinical experience in patients with severe renal impairment (see section 5.2). 
 
Paediatric population 
The safety and efficacy of Xospata in children aged below 18 years has not yet been established.  
No data are available. Due to in vitro binding to 5HT2B (see section 4.5), there is a potential impact on 
cardiac development in patients less than 6 months of age. 
 
Method of administration  
Xospata is for oral use.  
The tablets can be taken with or without food. They should be swallowed whole with water and should 
not be broken or crushed.  
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Differentiation syndrome  
Gilteritinib has been associated with differentiation syndrome (see section 4.8). Differentiation 
syndrome is associated with rapid proliferation and differentiation of myeloid cells and may be 
life-threatening or fatal if not treated. Symptoms and clinical findings of differentiation syndrome 
include fever, dyspnoea, pleural effusion, pericardial effusion, pulmonary oedema, hypotension, rapid 
weight gain, peripheral oedema, rash, and renal dysfunction.  
 
If differentiation syndrome is suspected, corticosteroid therapy should be initiated along with 
hemodynamic monitoring until symptom resolution. If severe signs and/or symptoms persist for more 
than 48 hours after initiation of corticosteroids, Xospata should be interrupted until signs and 
symptoms are no longer severe (see sections 4.2 and 4.8).  
 
Corticosteroids can be tapered after resolution of symptoms and should be administered for a 
minimum of 3 days. Symptoms of differentiation syndrome may recur with premature discontinuation 
of corticosteroid treatment. 
 
Posterior reversible encephalopathy syndrome  
There have been reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving 
Xospata (see section 4.8). PRES is a rare, reversible, neurological disorder which can present with 
rapidly evolving symptoms including seizure, headache, confusion, visual and neurological 
disturbances, with or without associated hypertension and altered mental status. If PRES is suspected, 
it should be confirmed by brain imaging, preferably magnetic resonance imaging (MRI). 
Discontinuation of Xospata in patients who develop PRES is recommended (see sections 4.2 and 4.8). 
 
Prolonged QT interval 
Gilteritinib has been associated with prolonged cardiac ventricular repolarisation (QT Interval) (see 
sections 4.8 and 5.1). QT prolongation can be observed in the first two months of treatment with 
gilteritinib. Therefore, electrocardiogram (ECG) should be performed prior to initiation of treatment, 
on day 8 and 15 of cycle 1, and prior to the start of the next three subsequent months of treatment. 
Caution is warranted in patients with relevant cardiac history. Hypokalaemia or hypomagnesaemia 



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may increase the QT prolongation risk. Hypokalaemia or hypomagnesaemia should therefore be 
corrected prior to and during Xospata treatment. 
 
Xospata should be interrupted in patients who have a QTcF >500 msec (see section 4.2).  
 
The decision to re-introduce gilteritinib treatment after an event of QT prolongation should be based 
on a careful consideration of benefits and risks. If Xospata is re-introduced at a reduced dose, ECG 
should be performed after 15 days of dosing, and prior to the start of the next three subsequent months 
of treatment. In clinical studies, 12 patients had QTcF >500 msec. Three patients interrupted and re-
initiated treatment without recurrence of QT prolongation. 
 
Pancreatitis 
There have been reports of pancreatitis. Patients who develop signs and symptoms suggestive of 
pancreatitis should be evaluated and monitored. Xospata should be interrupted and can be resumed at a 
reduced dose when the signs and symptoms of pancreatitis have resolved (see section 4.2).  
 
Interactions 
Co-administration of CYP3A/P-gp inducers may lead to decreased gilteritinib exposure and 
consequently a risk for lack of efficacy. Therefore, concomitant use of gilteritinib with strong 
CYP3A4/P-gp inducers should be avoided (see section 4.5). 
 
Caution is required when concomitantly prescribing gilteritinib with medicinal products that are strong 
inhibitors of CYP3A and/or P-gp (such as, but not limited to, voriconazole, itraconazole, posaconazole 
and clarithromycin ) because they can increase gilteritinib exposure. Alternative medicinal products 
that do not strongly inhibit CYP3A and/or P-gp activity should be considered. In situations where 
satisfactory therapeutic alternatives do not exist, patients should be closely monitored for toxicities 
during administration of gilteritinib (see section 4.5). 
 
Gilteritinib may reduce the effects of medicinal products that target 5HT2B receptor or sigma 
nonspecific receptors. Therefore, concomitant use of gilteritinib with these products should be avoided 
unless use is considered essential for the care of the patient (see section 4.5). 
 
Embryofoetal toxicity and contraception   
Pregnant women should be informed of the potential risk to a foetus (see sections 4.6 and 5.3). 
Females of reproductive potential should be advised to have a pregnancy test within seven days prior 
to starting treatment with Xospata and to use effective contraception during treatment with Xospata 
and for at least 6 months after stopping treatment. Women using hormonal contraceptives should add a 
barrier method of contraception. Males with female partners of reproductive potential should be 
advised to use effective contraception during treatment and for at least 4 months after the last dose of 
Xospata.  
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Gilteritinib is primarily metabolised by CYP3A enzymes, which can be induced or inhibited by a 
number of concomitant medicinal products. 
 
Effects of other medicinal products on Xospata 
CYP3A/P-gp Inducers 
Concomitant use of Xospata with strong CYP3A/P-gp inducers (e.g., phenytoin, rifampin and St. 
John’s Wort) should be avoided because they can decrease gilteritinib plasma concentrations. In 
healthy subjects, co-administration of rifampicin (600 mg), a strong CYP3A/P-gp inducer, to steady 
state with a single 20 mg dose of gilteritinib decreased gilteritinib mean Cmax by 27% and mean 
AUCinf by 70%, respectively, compared to subjects administered a single dose of gilteritinib alone (see 
section 4.4). 
 



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CYP3A and/or P-gp inhibitors 
Strong inhibitors of CYP3A and/or P-gp (e.g., voriconazole, itraconazole, posaconazole, 
clarithromycin, erythromycin, captopril, carvedilol, ritonavir, azithromycin) can increase gilteritinib 
plasma concentrations. A single, 10 mg dose of gilteritinib co-administered with itraconazole (200 mg 
once daily for 28 days), a strong CYP3A and/or P-gp inhibitor, to healthy subjects resulted in an 
approximate 20% increase in mean Cmax and 2.2-fold increase in mean AUCinf relative to subjects 
administered a single dose of gilteritinib alone. Gilteritinib exposure increased approximately 1.5-fold 
in patients with relapsed or refractory AML when co-administered with a strong CYP3A and/or P-gp 
inhibitor (see section 4.4). 
 
Gilteritinib as an inhibitor or inducer 
Gilteritinib is not an inhibitor or inducer of CYP3A4 or and inhibitor of MATE1 in vivo. The 
pharmacokinetics of midazolam (a sensitive CYP3A4 substrate) were not significantly (Cmax and AUC 
increased approximately 10%) affected after once-daily administration of gilteritinib (300 mg) for 15 
days in patients with FLT3-mutated relapsed or refractory AML. Additionally, the pharmacokinetics 
of cephalexin (a sensitive MATE1 substrate) were not significantly (Cmax and AUC decreased by less 
than 10%) affected after once daily administration of gilteritinib (200 mg) for 15 days in patients with 
FLT3-mutated relapsed or refractory AML. 
 
Effects of Xospata on other medicinal products 
5HT2B receptor or sigma nonspecific receptor 
Based on in vitro data, gilteritinib may reduce the effects of medicinal products that target 5HT2B 
receptor or sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant 
use of these medicinal products with Xospata unless use is considered essential for the care of the 
patient.  
 
4.6 Fertility, pregnancy and lactation 
 
Women of childbearing potential / Contraception in males and females 
Pregnancy testing is recommended for females of reproductive potential seven days prior to initiating 
Xospata treatment. Women of childbearing potential are recommended to use effective contraception 
(methods that result in less than 1% pregnancy rates) during and up to 6 months after treatment. It is 
unknown whether gilteritinib may reduce the effectiveness of hormonal contraceptives, and therefore 
women using hormonal contraceptives should add a barrier method of contraception. Males of 
reproductive potential should be advised to use effective contraception during treatment and for at 
least 4 months after the last dose of Xospata (see section 4.4).  
 
Pregnancy 
Gilteritinib can cause foetal harm when administered to pregnant women. There are no or limited 
amount of data from the use of gilteritinib in pregnant women. Reproductive studies in rats have 
shown that gilteritinib caused suppressed foetal growth, embryo-foetal deaths and teratogenicity (see 
section 5.3). Xospata is not recommended during pregnancy and in women of childbearing potential 
not using effective contraception.  
 
Breast-feeding 
It is unknown whether gilteritinib or its metabolites are excreted in human milk. Available animal data 
have shown excretion of gilteritinib and its metabolites in the animal milk of lactating rats and 
distribution to the tissues in infant rats via the milk (see section 5.3).  
 
A risk to the breast-fed children cannot be excluded. Breast-feeding should be discontinued during 
treatment with Xospata and for at least two months after the last dose. 
 
Fertility 
There are no data on the effect of gilterinitib on human fertility.  
 



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4.7 Effects on ability to drive and use machines 
 
Gilteritinib has minor influence on the ability to drive and use machines. Dizziness has been reported 
in patients taking Xospata and should be considered when assessing a patient’s ability to drive or use 
machines (see section 4.8). 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The safety of Xospata was evaluated in 319 patients with relapsed or refractory AML who have 
received at least one dose of 120 mg gilteritinib. 
 
The most frequent adverse reactions with gilteritinib were blood creatine phosphokinase increased 
(93.4%), alanine aminotransferase (ALT) increased (82.1%), aspartate aminotransferase (AST) 
increased (80.6%), blood alkaline phosphatase increased (68.7%), diarrhoea (35.1%), fatigue (30.4%), 
nausea (29.8%), constipation (28.2%), cough (28.2%), peripheral oedema (24.1%), dyspnea (24.1%), 
dizziness (20.4%), hypotension (17.2%), pain in extremity (14.7%), asthenia (13.8%), arthralgia 
(12.5%) and myalgia (12.5%). 
 
The most frequent serious adverse reactions were diarrhoea (4.7%), ALT increased (4.1%), dyspnea 
(3.4%), AST increased (3.1%) and hypotension (2.8%). Other clinically significant serious adverse 
reactions included differentiation syndrome (2.2%), electrocardiogram QT prolonged (0.9%) and 
posterior reversible encephalopathy syndrome (0.6%). 
 
Tabulated list of adverse reactions  
 
Adverse reactions observed during clinical studies are listed below by frequency category. Frequency 
categories are defined as follows: very common (≥1/10); common (≥1/100 to <1/10); uncommon 
(≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be 
estimated from the available data). Within each frequency grouping, adverse reactions are presented in 
order of decreasing seriousness. 
 
Table 2: Adverse reactions 

Adverse drug reaction 

All 
Grades 

% 

Grades 
≥3 
% 

Frequency 
category 

Immune system disorders 
Anaphylactic reaction 1.3 1.3 Common 
Nervous system disorders 
Dizziness 20.4 0.3 Very common 
Posterior reversible encephalopathy 
syndrome  0.6 0.6 Uncommon 
Cardiac disorders 
Electrocardiogram QT prolonged 8.8 2.5 Common 
Pericardial effusion 4.1 0.9 Common 
Pericarditis 1.6 0 Common 
Cardiac failure 1.3 1.3 Common 
Vascular disorders 
Hypotension 17.2 7.2 Very common 
Respiratory, thoracic and mediastinal disorders 
Cough 28.2 0.3 Very common 
Dyspnoea 24.1 4.4 Very common 
Differentiation syndrome 3.4 2.2 Common 
Gastrointestinal disorders 
Diarrhoea 35.1 4.1 Very common 



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Nausea 29.8 1.9 Very common 
Constipation 28.2 0.6 Very common 
Hepatobiliary disorders 
Alanine aminotransferase increased* 82.1 12.9 Very common 
Aspartate aminotransferase increased* 80.6 10.3 Very common 
Musculoskeletal and connective tissue disorders 
Blood creatine phosphokinase 
increased* 53.9 6.3 Very common 
Blood alkaline phosphatase increased* 68.7 1.6 Very common 
Pain in extremity 14.7 0.6 Very common 
Arthralgia 12.5 1.3 Very common 
Myalgia 12.5 0.3 Very common 
Musculoskeletal pain 4.1 0.3 Common 
Renal and urinary disorders 
Acute kidney injury 6.6 2.2 Common 
General disorders and administration site conditions 
Fatigue 30.4 3.1 Very common 
Peripheral oedema 24.1 0.3 Very common 
Asthenia 13.8 2.5 Very common 
Malaise 4.4 0 Common 
* Frequency is based on central laboratory values. 

 
Description of selected adverse reactions 
Differentiation syndrome 
Of 319 patients treated with Xospata in the clinical studies, 11 (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 clinical findings of 
differentiation syndrome in patients treated with Xospata included fever, dyspnoea, pleural effusion, 
pericardial effusion, pulmonary oedema, hypotension, rapid weight gain, peripheral oedema, rash, and 
renal dysfunction. Some cases had concomitant acute febrile neutrophilic dermatosis. Differentiation 
syndrome occurred as early as two days and up to 75 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. For 
recommendations in case of suspected differentiation syndrome see sections 4.2 and 4.4. 
 
PRES 
Of the 319 patients treated with Xospata in the clinical studies, 0.6% experienced posterior reversible 
encephalopathy syndrome (PRES). PRES is a rare, reversible, neurological disorder, which can 
present with rapidly evolving symptoms including seizure, headache, confusion, visual and 
neurological disturbances, with or without associated hypertension. Symptoms have resolved after 
discontinuation of treatment (see sections 4.2 and 4.4). 
 
QT prolongation 
Of the 317 patients treated with gilteritinib at 120 mg with a post-baseline QTC value in clinical 
studies, 4 patients (1%) experienced a QTcF >500 msec. Additionally, across all doses, 12 patients 
(2.3%) with relapsed/refractory AML had a maximum post-baseline QTcF interval >500 msec (see 
sections 4.2, 4.4 and 5.1).  
 
Reporting of suspected adverse reactions 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 

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4.9 Overdose 
 
There is no known specific antidote for Xospata. In the event of an overdose, patients must be closely 
monitored for signs or symptoms of adverse reactions, and appropriate symptomatic and supportive 
treatment initiated, taking into consideration the long half-life estimated at 113 hours. 
 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: antineoplastic agents, protein kinase inhibitors, ATC code: L01XE54 
 
Mechanism of action 
Gilteritinib fumarate is a FLT3 and AXL inhibitor.  
Gilteritinib inhibits FLT3 receptor signalling and proliferation in cells exogenously expressing FLT3 
including FLT3-ITD, FLT3-D835Y, and FLT3-ITD-D835Y, and it induced apoptosis in leukemic 
cells expressing FLT3-ITD. 
 
Pharmacodynamic effects 
In patients with relapsed or refractory AML receiving gilteritinib 120 mg, substantial (> 90%) 
inhibition of FLT3 phosphorylation was rapid (within 24 hours after first dose) and sustained, as 
characterised by an ex vivo plasma inhibitory activity (PIA) assay.  
 
Prolonged QT interval  
A concentration-related increase in change from baseline of QTcF was observed across gilteritinib 
doses ranging from 20 to 450 mg. The predicted mean change from baseline of QTcF at the mean 
steady-state Cmax (282.0 ng/mL) at the 120 mg daily dose was 4.96 msec with an upper 1-sided 95% 
CI = 6.20 msec.  
 
Clinical efficacy and safety 
Relapsed or refractory AML 
Efficacy and safety was evaluated in the active-controlled, phase 3 study (2215-CL-0301) . 
 
ADMIRAL study (2215-CL-0301) 
The ADMIRAL study is a Phase 3, open-label, multicentre, randomised clinical study of adult patients 
with relapsed or refractory AML with a FLT3 mutation as determined by the LeukoStrat® CDx FLT3 
Mutation Assay. In this study, 371 patients were randomised in a 2:1 ratio to receive gilteritinib or one 
of the following salvage chemotherapies (247 in the gilteritinib arm and 124 in the salvage 
chemotherapy arm): 

 
• cytarabine 20 mg twice daily by subcutaneous (SC) or intravenous (IV) for 10 days (days 1 

through 10) (LoDAC) 
• azacitidine 75 mg/m2 once daily by SC or IV for 7 days (days 1 through 7)  
• mitoxantrone 8 mg/m2, etoposide 100 mg/m2 and cytarabine 1000 mg/m2 once daily by IV for 5 

days (days 1 through 5) (MEC) 
• granulocyte colony-stimulating factor 300 mcg/m2 once daily by SC for 5 days (days 1 to 5), 

fludarabine 30 mg/m2 once daily by IV for 5 days (days 2 through 6), cytarabine 2000 mg/m2 
once daily by IV for 5 days (days 2 through 6), idarubicin 10 mg/m2 once daily by IV for 3 days 
(days 2 through 4) (FLAG-Ida). 

 
Patients included were relapsed or refractory after first line AML therapy and were stratified by 
response to prior AML treatment and preselected chemotherapy i.e. high or low intensity. While the 
study included patients with various AML-related cytogenetic abnormalities, patients with acute 
promyelocytic leukaemia (APL) or therapy-related AML were excluded. 
 



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Sixteen patients were randomised but not treated in the study (1 patient in the gilteritinib arm and 15 
patients in the chemotherapy arm). Gilteritinib was given orally at a starting dose of 120 mg daily until 
unacceptable toxicity or lack of clinical benefit. Dose reductions were allowed, to manage adverse 
reactions, and dose increases were allowed, for those patients who did not respond at the starting dose 
of 120 mg. 
 
Of the patients who were pre-selected to receive salvage chemotherapy, 60.5% were randomised to 
high intensity and 39.5% to low intensity. MEC and FLAG-Ida were given for up to two cycles 
depending on response to first cycle. LoDAC and azacitidine were given in continuous 4-week cycles 
until unacceptable toxicity or lack of clinical benefit. 
 
The demographic and baseline characteristics were well-balanced between the two treatment arms. 
The median age at randomisation was 62 years (range 20 to 84 years) in the gilteritinib arm and 62 
years (range 19 to 85 years) in the salvage chemotherapy arm. In the study 42% of patients were 65 
years or older and 12% were 75 years or older. Fifty-four percent of the patients were female. Most 
patients in the study were Caucasian (59.3%); 27.5% Asian, 5.7% Black, 4% other races and 3.5% 
unknown. The majority of patients (83.8%) had an ECOG performance status score of 0 or 1. Patients 
had the following confirmed mutations: FLT3-ITD alone (88.4%), FLT3-TKD alone (8.4%) or both 
FLT3-ITD and FLT3-TKD (1.9%). Twelve percent of patients received previous treatment with 
another FLT3 inhibitor. A majority of patients had AML with intermediate risk cytogenetics (73%), 
10% had unfavourable, 1.3% had favourable and 15.6% had unclassified cytogenetics.  
 
Prior to treatment with gilteritinib, 39.4% of patients had primary refractory AML and the majority of 
these patients were classified as refractory after 1 cycle of chemotherapy induction treatment, 19.7% 
had relapsed AML after an allogeneic haematopoietic stem cell transplant (HSCT) and 41% had 
relapsed AML with no allogeneic HSCT.  
 
The primary efficacy endpoint for the final analysis was OS in the intent-to-treat (ITT) population, 
measured from the date of randomisation until death by any cause (number of events analysed was 
261). Patients randomised to the gilteritinib arm had significantly longer survival compared to the 
chemotherapy arm (HR 0.637; 95% CI 0.490 – 0.830; 1 sided p-value: 0.0004). The median OS was 
9.3 months for patients receiving gilteritinib and 5.6 months for those receiving chemotherapy. 
Efficacy was further supported by the rate of complete remission (CR)/complete remission with partial 
haematologic recovery (CRh) (Table 3, Figure 1). 
 
Table 3: ADMIRAL study overall survival and complete remission in patients with relapsed or 
refractory AML 
 Gilteritinib 

(N=247) 
Chemotherapy 

(N=124) 
Overall survival 
Deaths, n (%) 171 (69.2) 90 (72.6) 
Median in months (95% CI) 9.3 (7.7, 10.7) 5.6 (4.7, 7.3) 
Hazard Ratio (95% CI) 0.637 (0.490, 0.830) 
p-value (1-sided) 0.0004 
1 year survival rate, % (95% CI) 37.1 (30.7, 43.6) 16.7 (9.9, 25) 
Complete remission 
CRa (95% CIb) 21.1% (16.1, 26.7) 10.5% (5.7, 17.3) 
CRhc (95% CIb) 13% (9, 17.8) 4.8% (1.8, 10.2) 
CR/CRh (95% CIb) 34% (28.1, 40.3) 15.3% (9.5, 22.9) 
CI: confidence interval 
a. CR was defined as an absolute neutrophil count ≥1.0 x 109/L, platelets ≥100 x 109/L, normal marrow 

differential with <5% blasts, must have been red blood cells, platelet transfusion independent and no 
evidence of extramedullary leukemia. 

b. The 95% CI rate was calculated using the exact method based on binomial distribution.  
c. CRh was defined as marrow blasts <5%, partial haematologic recovery absolute neutrophil count ≥0.5 

x 109/L and platelets ≥50 x 109/L, no evidence of extramedullary leukemia and could not have been 
classified as CR. 



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Figure 1: Kaplan-Meier plot of overall survival in ADMIRAL study 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
For patients who achieved a CR/CRh, the median time to first response was 3.7 months (range, 0.9 to 
10.6 months) in the gilteritinib arm and 1.2 months (range: 1 to 2.6 months) in the salvage 
chemotherapy arm. The median time to best response of CR/CRh was 3.8 months (range, 0.9 to 16 
months) in the gilteritinib arm and 1.2 months (range: 1 to 2.6 months) in the salvage chemotherapy 
arm. 
 
CHRYSALIS study (2215-CL-0101) 
The supportive Phase 1/2 dose-escalation study 2215-CL-0101 included 157 patients with FLT3 
mutated AML treated with either 1 or >1 prior lines of treatment in the combined dose group (i.e. 
80 mg, 120 mg or 200 mg);  31.2% received 1 prior line of treatment and 68.8% received >1 prior 
lines of treatment.  
 
The response rate (CR/CRh) observed in Study 2215-CL-0101 in the patients who received more than 
1 line of prior therapy was 21.4% and 15.7% for the 120 mg dose and the combined dose levels, 
respectively. The median OS was 7.2 months and 7.1 months for the 120 mg dose and the combined 
dose levels, respectively. 
 
Paediatric population 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
Xospata in one or more subsets of the paediatric population in the treatment of acute myeloid 
leukaemia. See 4.2 for information on paediatric use. 
 
5.2 Pharmacokinetic properties 
 
Absorption 
Following oral administration of gilteritinib, peak plasma concentrations are observed at a median tmax 
approximately between 4 and 6 hours in healthy volunteers and patients with relapsed or 
refractory AML. Gilteritinib undergoes first-order absorption with an estimated absorption rate (ka) of 
0.43 h-1 with a lag time of 0.34 hours based on population PK modelling. Median steady-state 
maximum concentration (Cmax) is 282.0 ng/mL (CV% = 50.8), and area under the plasma 
concentration curve during 24-hour dosing interval (AUC0-24) is 6180 ng·h/mL (CV% = 46.4) after 
once-daily dosing of 120 mg gilteritinib. Steady-state plasma levels are reached within 15 days of 
once-daily dosing with an approximate 10-fold accumulation. 
 



12 

Effect of food 
In healthy adults, gilteritinib Cmax and AUC decreased by approximately 26% and less than 10%, 
respectively, when a single 40 mg dose of gilteritinib was co-administered with a high fat meal 
compared to gilteritinib exposure in fasted state. Median tmax was delayed 2 hours when gilteritinib 
was administered with a high-fat meal. 
 
Distribution 
The population estimate of central and peripheral volume of distribution were 1092 L and 1100 L, 
respectively. These data indicate gilteritinib distributes extensively outside of plasma, which may 
indicate extensive tissue distribution. In vivo plasma protein binding in humans is approximately 90% 
and gilteritinib is primarily bound to albumin.  
 
Biotransformation 
Based on in vitro data, gilteritinib is primarily metabolised via CYP3A4. The primary metabolites in 
humans include M17 (formed via N-dealkylation and oxidation), M16 and M10 (both formed via 
N-dealkylation) and were observed in animals. None of these three metabolites exceeded 10% of 
overall parent exposure. The pharmacological activity of the metabolites against FLT3 and AXL 
receptors is unknown.  
 
Transporter drug-drug interactions 
In vitro experiments demonstrated that gilteritinib is a P-gp substrate and may potentially inhibit 
BCRP and P-gp in the small intestine, OCT1 in the liver at clinically relevant concentrations (see 
section 4.5).  
 
Elimination 
After a single dose of [14C] -gilteritinib, gilteritinib is primarily excreted in faeces with 64.5% of the 
total administered dose recovered in faeces. Approximately 16.4% of the total dose was excreted in 
urine as unchanged drug and metabolites. Gilteritinib plasma concentrations declined in a 
bi-exponential manner with a population mean estimated half-life of 113 hours. The estimated 
apparent clearance (CL/F) based on the population PK model is 14.85 L/h. 
 
Linearity/non-linearity 
In general, gilteritinib exhibited linear, dose-proportional pharmacokinetics after single and multiple 
dose administration at doses ranging from 20 to 450 mg in patients with relapsed or refractory AML.  
 
Special populations 
A population pharmacokinetic analysis was performed to evaluate the impact of intrinsic and extrinsic 
covariates on the predicted exposure of gilteritinib in patients with relapsed or refractory AML. 
Covariate analysis indicated that age (20 years to 90 years), and body weight (36 kg to 157 kg) were 
statistically significant; however predicted change in gilteritinib exposure was less than 2-fold. 
 
Hepatic impairment 
The effect of hepatic impairment on gilteritinib pharmacokinetics was studied in subjects with mild 
(Child-Pugh Class A) and moderate (Child-Pugh Class B) hepatic impairment. Results indicate 
unbound gilteritinib exposure in subjects with mild or moderate hepatic impairment is comparable to 
that observed in subjects with normal hepatic function. The effect of mild hepatic impairment [as 
defined by NCI-ODWG] on gilteritinib exposure was also assessed using the population PK model 
and the results demonstrate little difference in predicted steady-state gilteritinib exposure relative to a 
typical patient with relapsed or refractory AML and normal liver function. 
 
Gilteritinib has not been studied in patients with severe hepatic impairment (Child-Pugh Class C). 
 
Renal impairment 
A dedicated renal impairment study has not been conducted to assess of the effect of renal impairment 
on gilteritinib pharmacokinetics. The effect of mild or moderate renal impairment was evaluated using 
a population pharmacokinetic model. Serum creatinine, a marker of renal function, was identified as a 
statistically significant covariate. However, the predicted increase on gilteritinib exposure was less 



13 

than 2-fold. The effect of severe renal impairment on gilteritinib exposure has not been investigated 
(see section 4.2). 
 
5.3 Preclinical safety data 
 
Adverse reactions not observed in clinical studies, but seen in animals (safety pharmacology/repeat 
dose toxicity) at exposure levels similar to clinical exposure levels and with possible relevance to 
clinical use were as follows: 
 
Safety pharmacology 
In rats, decreased urination at 30 mg/kg and higher and decreased defecation at 100 mg/kg were 
observed. In dogs, positive faecal occult blood at 10 mg/kg and higher, a decrease in the blood calcium 
concentration at 30 mg/kg, and salivation and an increase followed by a decrease in the blood calcium 
concentration at 100 mg/kg were observed. These changes were observed at plasma exposure levels 
similar to or less than clinical exposure levels. A possible clinical relevance of these findings is 
unknown. 
 
Repeat dose toxicity 
In the repeated dose toxicity studies in rats and dogs, target organs of toxicity were the gastrointestinal 
tract (heamorrhage in dogs), lymphohaematopoietic system (lymphocyte necrosis and bone marrow 
hypocellularity with changes in haematological parameters), eye (inflammation and lens opacity in 
rats, fundus colour change in dogs, retinal vacuolation), lung (interstitial pneumonia in rats and 
inflammation in dogs), kidney (renal tubule changes with a positive urine occult blood reaction) and 
liver (hepatocyte vacuolation), urinary bladder (epithelial vacuolation), epithelial tissue (ulcer and 
inflammation), and phospholipidosis (lung and kidney in rats). These changes were observed at 
plasma exposure levels similar to or less than clinical exposure levels. Reversibility of most of the 
changes was indicated by the end of the 4-week recovery period. A possible clinical relevance of these 
findings is unknown. 
 
Genotoxicity 
Gilteritinib did not induce gene mutation or chromosomal aberrations in vitro. The in vivo 
micronucleus test showed that gilteritinib has a potential to induce micronuclei in mice. 
 
Reproductive toxicity 
Gilteritinib showed suppressed foetal growth, and induced embryo-foetal deaths and teratogenicity in 
the embryo-foetal development studies in rats at exposure levels similar to clinical exposure levels. 
Placental transfer of gilteritinib was shown in the rat resulting in transfer of radioactivity to the foetus 
similar to that observed in maternal plasma.  
 
Gilteritinib was excreted into the milk of lactating rats with milk concentrations being higher than in 
maternal plasma. Gilteritinib was distributed through the breast milk to different tissues, except for the 
brain, of suckling rats. 
 
Juvenile animal toxicity study 
In the juvenile toxicity study in rats, the minimum lethal dose level (2.5 mg/kg/day) was much lower 
than that of adult rats (20 mg/kg/day). The gastrointestinal tract was identified as one of the target 
organs similar as in adult rats. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Tablet core 
Mannitol (E421) 
Hydroxypropylcellulose  
Hydroxypropylcellulose, low-substituted 



14 

Magnesium stearate  
 
Film-coating 
Hypromellose  
Talc 
Macrogol 
Titanium dioxide 
Iron oxide yellow (E172) 
 
6.2 Incompatibilities 
 
Not applicable  
 
6.3 Shelf life 
 
4 years. 
 
6.4 Special precautions for storage 
 
This medicinal product does not require any special temperature storage conditions. Store in the 
original package in order to protect from light. 
 
6.5 Nature and contents of container  
 
OPA/aluminium/PVC/aluminium blisters containing 21 film-coated tablets.  
 
Each pack contains 84 film-coated tablets. 
 
6.6 Special precautions for disposal  
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1399/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
 
10. DATE OF REVISION OF THE TEXT 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu. 
 
  

http://www.ema.europa.eu/


15 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE 

 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE 

MARKETING AUTHORISATION 
 

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT 



16 

A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer responsible for batch release 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62  
2333 BE Leiden 
The Netherlands 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE  
 
Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2). 
 
 
C.  OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION 
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs for this medicinal product are set out in the list of 
Union reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC 
and any subsequent updates published on the European medicines web-portal. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 
6 months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT   
 
• Risk management plan (RMP) 
 
The marketing authorisation holder (MAH) shall perform the required pharmacovigilance 
activities and interventions detailed in the agreed RMP presented in Module 1.8.2 of the 
marketing authorisation and any agreed subsequent updates of the RMP. 
 
An updated RMP should be submitted: 
• At the request of the European Medicines Agency; 
• Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached. 

 
• Additional risk minimisation measures  
 
Prior to the launch of Xospata in each Member State the MAH must agree about the content and 
format of the physician educational material, including communication media, distribution modalities, 
and any other aspects of the programme, with the National Competent Authority. The patient alert 
card will be integrated in the packaging and the content will be agreed as part of the labelling (Annex 
III). 
 
The educational material is aimed at haematologists who treat patients with leukemias including AML, 
and patients with AML prescribed Xospata to further inform prescribers and patients regarding the 
important identified risk of differentiation syndrome. 
 



17 

The MAH shall ensure that in each Member State where Xospata is marketed, haematologists who are 
expected to prescribe Xospata, and patients who are expected to use Xospata are provided with the 
following educational materials: 
• Physician educational material   
• Patient Alert Card 
 
Physician educational material: 
• The Summary of Product Characteristics 
• Educational tool targeting prescribers  

o Educational tool targeting prescribers:  
- Information on Xospata, including the approved indication according to the SmPC. 
- Description of the signs and symptoms of differentiation syndrome. 
- Management of differentiation syndrome.  

 
The patient information pack: 
• Patient information leaflet 
• Patient alert card 

o Patient alert card:  
- Information for patients that Xospata treatment may cause differentiation 

syndrome. 
- Description of signs or symptoms of the safety concern and when to seek medical 

care if differentiation syndrome is suspected 
- A warning message for healthcare professionals treating the patient at any time, 

including in conditions of emergency, that the patient is using Xospata. 
- Contact details of the treating physician who has prescribed Xospata. 
- Needs to be carried all the time and presented to any healthcare professional. 

 
  



18 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



19 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



20 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON WITH BLUE BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xospata 40 mg film-coated tablets  
gilteritinib  
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
Each film-coated tablet contains 40 mg gilteritinib (as fumarate). 
 
 
3. LIST OF EXCIPIENTS 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
84 film-coated tablets 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Oral use. 
Do not break or crush the tablets. 
Read the package leaflet before use. 
 
 
6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 

OF THE SIGHT AND REACH OF CHILDREN 
 
Keep out of the sight and reach of children. 
 
 
7. OTHER SPECIAL WARNING(S), IF NECESSARY 
 
 
8. EXPIRY DATE 
 
EXP 
 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in the original package in order to protect from light. 
 
 
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE 

 
 



21 

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1399/001  84 film coated tablets 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
xospata 40 mg  
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC  
SN  
NN  
 
 
  



22 

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Xospata 40 mg film-coated tablets 
gilteritinib 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Astellas 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 
 
  



23 

CONTENT OF PATIENT ALERT CARD 
 
PATIENT ALERT CARD 
 
XOSPATA®  
(gilteritinib)  
• Carry this card with you at all times, especially when you travel or when you see another 

doctor.  
• Please ensure you show this card to any doctor, pharmacist or nurse for any medical treatment 

or at any visits to the hospital or clinic. 
• Please contact your doctor immediately, if you develop any side effects, in particular those 

listed on this card. 
 
IMPORTANT SAFETY INFORMATION FOR PATIENTS  
 
Xospata may cause serious side effects, including differentiation syndrome. 
Differentiation syndrome is a condition that affects your blood cells and may be life-threatening or 
lead to death if not treated in a timely manner.  
Talk to your doctor, pharmacist or nurse immediately if you have any of the following symptoms: 
• Fever 
• Trouble Breathing 
• Rash 
• Dizziness or lightheadedness 
• Rapid weight gain 
• Swelling of your arms or legs 
Differentiation syndrome can happen any time during the first 3 months of treatment from as early as 
2 days after starting treatment. Getting medical treatment early may stop the problem from becoming 
more serious. 
 
Your doctor will monitor you, may pause your treatment and/or may give you a medicine to treat your 
condition. 
 
If you have any further questions about your treatment, please contact your doctor. 
 
IMPORTANT INFORMATION FOR HEALTHCARE PROVIDERS 
 
• This patient is being treated with Xospata (gilteritinib), which can cause differentiation 

syndrome.  
• Symptoms include fever, dyspnoea, pleural effusion, pericardial effusion, pulmonary oedema, 

hypotension, rapid weight gain, peripheral oedema, rash, and renal dysfunction.  
• If differentiation syndrome is suspected, corticosteroid therapy should be initiated along with 

hemodynamic monitoring until symptom resolution.  
• If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, 

Xospata should be interrupted until signs and symptoms are no longer severe. 
Please contact the patient’s Haematologist/Oncologist for more information and consult the Product 
Information for gilteritinib available at https://www.ema.europa.eu/. 
 
My name: ________________________________________________________________________ 
My contact number: ____________________________________________________________ 
Emergency contact: ________________________________________________________________ 
Emergency contact number: ________________________________________________________ 
Name of Haematologist/Oncologist/Oncology Nurse: _____________________________________ 
Contact number: _______________________________________________________________ 
After-hours contact number: _____________________________________________________ 
Name of my Hospital: ______________________________________________________________ 
My Hospital contact number: ____________________________________________________  

https://www.ema.europa.eu/


24 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



25 

Package leaflet: Information for the patient 
 

Xospata 40 mg film-coated tablets 
gilteritinib 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.  
- If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What Xospata is and what it is used for  
2. What you need to know before you take Xospata  
3. How to take Xospata  
4. Possible side effects  
5. How to store Xospata  
6. Contents of the pack and other information 
 
 
1. What Xospata is and what it is used for 
 
What Xospata is 
Xospata belongs to a class of cancer medicines called protein kinase inihibitors. It contains the active 
substance gilteritinib.  
 
What Xospata is used for 
Xospata is used to treat adults with acute myeloid leukaemia (AML), a cancer of certain white blood 
cells. Xospata is used if AML is linked to an alteration of a gene called FLT3, and is given to patients 
whose disease has come back or has not improved after previous treatment.  
 
How Xospata works  
In AML, patients develop large numbers of abnormal white blood cells. Gilteritinib blocks the action 
of certain enzymes (kinases) needed for the abnormal cells to multiply and grow, thus preventing the 
growth of the cancer. 
 
 
2. What you need to know before you take Xospata  
 
Do not take Xospata 
- if you are allergic to gilteritinib or any of the other ingredients of this medicine (listed in section 

6). 
 
Warnings and precautions  
Talk to you doctor, pharmacist or nurse straight away: 
- if you have any of the following symptoms: fever, trouble breathing, rash, dizziness or 

lightheadedness, rapid weight gain, swelling of your arms or legs. These may be signs of a 
condition called differentiation syndrome (see section 4 – Possible side effects). Differentiation 



26 

syndrome can happen any time during the first 3months of Xospata treatment from as early as 2 
days after starting. If it occurs, your doctor will monitor you and may give you a medicine to 
treat your condition. She or he may also pause Xospata treatment until symptoms are reduced. 
You will also find this information in the Patient Alert Card that is included in the packaging. It 
is important that you keep this Alert Card with you and show it to any healthcare professional 
you see.  

- if you have a seizure or quickly worsening symptoms such as headache, decreased alertness, 
confusion, blurred vision or other problems with seeing. These may be signs of a condition 
called PRES (see section 4. – Possible side effects). Your doctor may do a test to check if you 
have developed PRES and will stop Xospata treatment if it is confirmed that you have PRES. 

 
Talk to your doctor, pharmacist or nurse before taking Xospata: 
- if you have a heart rhythm disorder, such as an irregular heartbeat or a condition called QT 

prolongation (see section 4. – Possible side effects). 
- if you have a history of low levels of the salts potassium or magnesium in your blood, as this 

may increase the risk of an abnormal heart rhythm. 
- if you have severe pain in the upper abdomen and back, nausea and vomiting. These may be 

signs of an inflammation of the pancreas (pancreatitis). 
 
Additional monitoring during treatment with Xospata 
Your doctor will carry out regular blood tests before and during treatment with Xospata. Your doctor 
will also regularly check your heart function before and during treatment. 
 
Children and adolescents 
Do not give Xospata to children and adolescents under 18 years because it is not known whether it is 
safe and effective in this age group. 
 
Other medicines and Xospata 
Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other 
medicines. Xospata may affect the way these medicines work, or these medicines may affect how 
Xospata works. 
 
In particular, tell your doctor, pharmacist or nurse if you are taking any of the following medicines: 
- medicines used to treat tuberculosis, such as rifampicin;  
- medicines used to treat epilepsy, such as phenytoin;  
- medicines used to treat fungal infections such as voriconazole, posaconazole or itraconazole; 
- medicines used to treat bacterial infections such as erythromycin, clarithromycin or 

azithromycin; 
- medicines used to treat high blood pressure (hypertension) such as captopril or carvedilol; 
- medicines used to treat infections with the human immunodeficiency virus (HIV) such as 

ritonavir; 
- medicines used to treat depression such as escitalopram, fluoxetine or sertraline; 
- St. John’s wort (also known as Hypericum perforatum), a herbal medicine used to treat 

depression. 
 
If you normally take any of these medicines, your doctor might change it and prescribe a different 
medicine for you during your treatment with Xospata. 
 
Pregnancy and breast-feeding 
Xospata may harm your unborn baby and should not be used during pregnancy. Women taking 
Xospata who are able to become pregnant should use an effective method of contraception during 
treatment with Xospata and for at least 6 months after stopping Xospata. If you use a hormonal 
contraceptive, you must also use a barrier method, such as a condom or a diaphragm. Men taking 
Xospata whose partners are able to become pregnant should use an effective method of contraception 
during treatment of Xospata and for at least 4 months after stopping the treatment. 
 



27 

It is not known if Xospata passes into your breast milk and could harm your baby. You should not 
breast-feed during treatment with Xospata and for at least 2 months after stopping the treatment. 
 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor, 
pharmacist or nurse for advice before taking this medicine. 
 
Driving and using machines 
You may feel dizzy after taking Xospata. If this happens, do not drive or use machines. 
 
 
3. How to take Xospata 
 
Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
Xospata is taken by mouth as tablets. 
 
Your doctor will tell you what dose of Xospata to take. The recommended dose is 120 mg (three 
tablets) once a day. Your doctor may decide to increase or lower your dose or temporarily interrupt 
treatment. Continue treatment at the dose prescribed by your doctor. 
 
Taking Xospata 
- Take Xospata once a day at the same time each day. 
- Swallow the tablets whole with water. 
- Do not break or crush the tablets. 
- Xospata can be taken with or without food. 
- Continue taking Xospata for as long as your doctor tells you.  
 
If you take more Xospata than you should 
If you take more tablets than you should, contact your doctor. 
 
If you forget to take Xospata 
If you forget to take Xospata at the usual time, take your usual dose as soon as you remember on the 
same day and take your next dose at the usual time on the following day. Do not take a double dose to 
make up for a forgotten dose. 
 
If you stop taking Xospata 
Do not stop taking this medicine unless your doctor tells you to. 
 
If you have any further questions on the use of this medicine, ask your doctor. 
 
 
4. Possible side effects 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Some possible side effects may be serious: 
- Differentiation syndrome. Contact your doctor straight away if you have any of the following 

symptoms: fever, trouble breathing, rash, dizziness or lightheadedness, rapid weight gain, 
swelling of your arms or legs. These may be signs of a condition called differentiation syndrome 
(may affect up to 1 in 10 people). 

- Posterior reversible encephalopathy syndrome (PRES). Contact your doctor straight away if 
you have a seizure, quickly worsening headache, confusion, or other vision problems.There 
have been uncommon reports of a condition involving the brain, in patients treated with 
Xospata, called PRES (may affect up to 1 in 100 people).  

- Heart rhythm problems (QT prolongation). Contact your doctor straight away if you have a 
change in your heartbeat, or if you feel dizzy, lightheaded, or faint. Xospata may cause a heart 
problem called QT prolongation (may affect up to 1 in 10 people).  



28 

 
Other possible side effects 
 
Very common (may affect more than 1 in 10 people): 
- diarrhoea 
- nausea 
- constipation 
- tiredness 
- swelling due to fluid retention (oedema) 
- loss of energy, weakness (asthenia) 
- abnormal blood test results: high levels of blood creatine phosphokinase (indicative of muscle or 

heart function), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or blood 
alkaline phosphatase (indicative of liver function) 

- pain in limbs 
- joint pain (arthralgia) 
- muscle pain (myalgia) 
- cough 
- shortness of breath (dyspnoea) 
- dizziness 
- low blood pressure (hypotension) 
 
Common (may affect up to 1 in 10 people): 
- collection of fluid around the heart, which, if severe, can decrease the heart’s ability to pump 

blood (pericardial effusion) 
- a vague feeling of discomfort, feeling unwell (malaise) 
- a severe life-threatening allergic reaction, e.g., swelling in the mouth, tongue, face and throat, 

itching, hives (anaphylactic reaction) 
- muscle stiffness 
- passing less urine, swelling in the legs (signs of sudden kidney injury) 
 
Uncommon (may affect up to 1 in 100 people): 
- inflammation of the heart (pericarditis) 
- heart failure 
 
Reporting of side effects 
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects 
not listed in this leaflet. You can also report side effects directly via the national reporting system 
listed in Appendix V. By reporting side effects you can help provide more information on the safety of 
this medicine. 
 
 
5. How to store Xospata 
Keep this medicine out of the sight and reach of children. 
 
Do not use this medicine after the expiry date which is stated on the carton and the blister after EXP. 
The expiry date refers to the last day of that month. 
 
Store in the original package in order to protect from light. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


29 

6. Contents of the pack and other information 
 
What Xospata contains  
- The active substance is gilteritinib. Each film-coated tablet contains 40 mg gilteritinib (as 

fumarate). 
- The other ingredients are: mannitol (E421), hydroxypropylcellulose, low-substituted 

hydroxypropylcellulose, magnesium stearate, hypromellose, talc, macrogol, titanium dioxide, 
iron oxide yellow (E172). 

 
What Xospata looks like and contents of the pack 
Xospata 40 mg film-coated tablets are round, light yellow film-coated tablets with the company logo 
and ‘235’ debossed on one side of the tablet.  
 
The tablets are provided in blisters and are available in packs containing 84 film-coated tablets 
(4-blisters of 21 film-coated tablets). 
 
Marketing Authorisation Holder and Manufacturer 
Astellas Pharma Europe B.V. 
Sylviusweg 62 
2333 BE Leiden 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Astellas Pharma B.V. Branch 
Tél/Tel: +32 (0)2 5580710 
 

Lietuva 
Biocodex UAB 
Tel.: +370 37 408 681 
 

България 
Астелас Фарма ЕООД 
Teл.: +359 2 862 53 72 
 

Luxembourg/Luxemburg 
Astellas Pharma B.V. Branch 
Belgique/Belgien 
Tél/Tel: +32 (0)2 5580710 
 

Česká republika 
Astellas Pharma s.r.o. 
Tel: +420 221 401 500 
 

Magyarország 
Astellas Pharma Kft. 
Tel.: +36 1 577 8200 
 

Danmark 
Astellas Pharma a/s 
Tlf: +45 43 430355 
 

Malta 
Astellas Pharmaceuticals AEBE 
Tel: +30 210 8189900  

Deutschland 
Astellas Pharma GmbH 
Tel.: +49 (0)89 454401 
 

Nederland 
Astellas Pharma B.V. 
Tel: +31 (0)71 5455745 
 

Eesti 
Biocodex OÜ 
Tel: +372 6 056 014 
 

Norge 
Astellas Pharma 
Tlf: +47 66 76 46 00 
 

Ελλάδα 
Astellas Pharmaceuticals AEBE 
Τηλ: +30 210 8189900 
 

Österreich 
Astellas Pharma Ges.m.b.H. 
Tel.: +43 (0)1 8772668 
 



30 

España 
Astellas Pharma S.A. 
Tel: +34 91 4952700 
 

Polska 
Astellas Pharma Sp.z.o.o. 
Tel.: +48 225451 111 

France 
Astellas Pharma S.A.S. 
Tél: +33 (0)1 55917500 
 

Portugal 
Astellas Farma, Lda. 
Tel: +351 21 4401320 

Hrvatska 
Astellas d.o.o 
Tel: +385 1670 0102 
 

România 
S.C.Astellas Pharma SRL 
Tel: +40 (0)21 361 04 95/96/92 
 

Ireland 
Astellas Pharma Co. Ltd. 
Tel: +353 (0)1 4671555 
 

Slovenija 
Astellas Pharma d.o.o 
Tel: +386 14011400 
 

Ísland 
Vistor hf 
Sími: +354 535 7000 
 

Slovenská republika 
Astellas Pharma s.r.o. 
Tel: +421 2 4444 2157 
 

Italia 
Astellas Pharma S.p.A. 
Tel: +39 (0)2 921381 
 

Suomi/Finland 
Astellas Pharma 
Puh/Tel: +358 (0)9 85606000 

Κύπρος 
Ελλάδα 
Astellas Pharmaceuticals AEBE 
Τηλ: +30 210 8189900 
 

Sverige 
Astellas Pharma AB 
Tel: +46 (0)40-650 15 00 
 

Latvija 
Biocodex SIA 
Tel: +371 67 619365 

United Kingdom 
Astellas Pharma Ltd. 
Tel: +44 (0) 203 379 8700 
 

 
 
This leaflet was last revised in MM/YYYY 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET