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Xospata is a brand name for Gilteritinib. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: 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).
Verbatim from this product's EMA label. Tap a section to expand.
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. 4). 8). 6). 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. 3 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.
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.
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. 5%). 8%). 6%). Tabulated list of adverse reactions Adverse reactions observed during clinical studies are listed below by MedDRA system oragan class and 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. 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 one day and up to 82 days after Xospata initiation and has been observed with or without concomitant leukocytosis. Of the 11 patients who experienced differentiation 9 syndrome, 9 (82%) recovered after treatment or after dose interruption of Xospata.
4. 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.
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. 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. 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). 8). 1). QT prolongation can be observed in the first three 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 may increase the QT prolongation risk. Hypokalaemia or hypomagnesaemia should therefore be corrected prior to and during gilteritinib treatment.
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 gilteritinib 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.
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b. The daily dose can be reduced from 120 mg to 80 mg or from 200 mg to 120 mg. c. 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).
2). 4 Hepatic impairment No dose adjustment is required for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment. 2). 2). Paediatric population The safety and efficacy of Xospata in children aged below 18 years has not yet been established.
No data are available. 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.
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.
4). QT prolongation Of the 317 patients treated with Xospata at 120 mg with a post-baseline QTC value in clinical studies, 4 patients (1%) experienced a QTcF >500 msec. 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.
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.
2). Severe renal impairment Gilteritinib exposure may be increased in patients with severe renal impairment or end stage renal disease. 2). Interactions Co-administration of CYP3A/P-gp inducers may lead to decreased gilteritinib exposure and consequently a risk for lack of efficacy.
5). Caution is required when concomitantly prescribing gilteritinib with medicinal products that are strong inhibitors of CYP3A, P-gp and/or breast cancer resistant protein (BCRP) because they can increase gilteritinib exposure. Alternative medicinal products that do not strongly inhibit CYP3A, P-gp and/or BCRP activity should be considered.
5). Gilteritinib may reduce the effects of medicinal products that target 5HT2B receptor or sigma nonspecific receptors. 5). 3). Females of reproductive potential should be advised to have a pregnancy test within seven days prior to starting treatment with gilteritinib and to use effective contraception during treatment with gilteritinib 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 gilteritinib.
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