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  • Xospata 40 mg
    / Astellas


    Active Ingredient

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    30

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    Related information


    Dosage

    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.
    Gilteritinib may be re‑initiated in patients following haematopoietic stem cell transplantation (HSCT).
    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 prescribing information for full details.
    Treatment should continue until the patient is no longer clinically benefiting from Gilteritinib 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 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.


    Indications

    Indicated as monotherapy for the treatment of adult patients who have relapsed or refractory acute myeloid leukaemia (AML) with a FLT3 mutation.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    Differentiation syndrome: Gilteritinib has been associated with 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 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, Gilteritinib  should be interrupted until signs and symptoms are no longer severe.
    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 Gilteritinib . Discontinuation of Gilteritinib  in patients who develop PRES is recommended.
    Prolonged QT interval: Gilteritinib has been associated with prolonged cardiac ventricular repolarisation (QT Interval). 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 may increase the QT prolongation risk. Hypokalaemia or hypomagnesaemia should therefore be corrected prior to and during Gilteritinib treatment.
    Gilteritinib should be interrupted in patients who have a QTcF >500 msec.
    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. 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. Gilteritinib  should be interrupted and can be resumed at a reduced dose when the signs and symptoms of pancreatitis have resolved.
    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.
    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.
    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.
    Embryofoetal toxicity and contraception: Pregnant women should be informed of the potential risk to a foetus. 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.
    See prescribing information for full details


    Side Effects

    Blood creatine phosphokinase increased, alanine aminotransferase (alt) increased, aspartate aminotransferase (ast) increased, blood alkaline phosphatase increased, diarrhoea, fatigue, nausea, constipation, cough, peripheral oedema, dyspnea, dizziness, hypotension, pain in extremity, asthenia, arthralgia and myalgia.
    See prescribing information for full details.


    Drug interactions

    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 Gilteritinib

    CYP3A/P gp Inducers

    Concomitant use of Gilteritinib  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.

    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.

     

    Gilteritinib as an inhibitor or inducer

    Gilteritinib is not an inhibitor or inducer of CYP3A4 or and inhibitor of MATE1 in vivo.

    Effects of Gilteritinib  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 Gilteritinib  unless use is considered essential for the care of the patient.

    See prescribing information for full details.


    Pregnancy and Lactation

    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 Gilteritinib

    CYP3A/P gp Inducers

    Concomitant use of Gilteritinib  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.

    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.

     

    Gilteritinib as an inhibitor or inducer

    Gilteritinib is not an inhibitor or inducer of CYP3A4 or and inhibitor of MATE1 in vivo.

    Effects of Gilteritinib  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 Gilteritinib  unless use is considered essential for the care of the patient. See prescribing information for full details.

    Lactation:

    It is unknown whether gilteritinib or its metabolites are excreted in human milk.

    A risk to the breast‑fed children cannot be excluded. Breast‑feeding should be discontinued during treatment with Gilteritinib  and for at least two months after the last dose.

    See prescribing information for full details.

                           


    Overdose

    There is no known specific antidote for Gilteritinib . 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.


    Manufacturer
    Astellas Pharma Europe BV, The Netherlands
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