Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: Astellas Pharma Europe B.V., Sylviusweg 62, 2333 BE Leiden, The Netherlands
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).
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).
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. In the absence of a response [patient did not achieve a composite complete remission (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.
Table 1. Xospata dose interruption, reduction and discontinuation recommendations in patients with relapsed or refractory AML:
| Criteria | Xospata dosing |
|---|---|
| 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. |
| Posterior reversible encephalopathy syndrome | • Discontinue gilteritinib. |
| QTcF interval >500 msec | • Interrupt gilteritinib. • Resume gilteritinib at a reduced dose (80 mg or 120 mgb) when QTcF interval returns to within 30 msec of baseline or ≤480 msec. |
| QTcF 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. |
| 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 CRcc. |
a Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, 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. 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 × 109/L)] and CRi (achieved all criteria for CR except for incomplete haematological recovery with residual neutropenia <1 × 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.
No dose adjustment is required in patients ≥65 years of age (see section 5.2).
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).
No dose adjustment is necessary in patients with mild, moderate or severe renal impairment (see sections 4.4 and 5.2).
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.
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.
There is no known specific antidote for Xospata. In the event of an overdose, treatment with Xospata should be stopped. 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.
4 years.
This medicinal product does not require any special temperature storage conditions. Store in the original package in order to protect from light.
OPA/aluminium/PVC/aluminium blisters containing 21 film-coated tablets.
Each pack contains 84 film-coated tablets.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
