Oral Refractory acute myeloid leukaemia with FLT3 mutation, Relapsed acute myeloid leukaemia with FLT3 mutation
Adult: Initially, 120 mg once daily. Continue treatment for at least 6 months or until disease progression or unacceptable toxicity occurs. If no response (did not achieve composite complete remission [CRc]) is observed after 4 weeks, dose may be increased to 200 mg once daily if tolerated. Dose reduction, dosing interruption, or discontinuation may be required if serious adverse effects occur (refer to specific product guidelines).
May be taken with or without food. Swallow whole, do not break/crush/chew.
Pregnancy and lactation.
Patient with relevant cardiac history, risk factors for QT-interval prolongation (e.g. hypokalaemia, hypomagnesaemia).
Significant: Prolonged QT interval, pancreatitis, hypersensitivity reactions (e.g. anaphylactic reactions). Rarely, posterior reversible encephalopathy syndrome. Blood and lymphatic system disorders: Febrile neutropenia. Cardiac disorders: Pericardial effusion, pericarditis, cardiac failure. Gastrointestinal disorders: Diarrhoea, nausea, constipation. General disorders and administration site conditions: Fatigue, asthenia, peripheral oedema, malaise. Investigations: Increased ALT, AST, blood creatine phosphokinase, and alkaline phosphatase. Musculoskeletal and connective tissue disorders: Arthralgia, myalgia, pain in extremity, musculoskeletal pain. Nervous system disorders: Dizziness. Renal and urinary disorders: Acute kidney injury. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea. Skin and subcutaneous tissue disorders: Rash. Vascular disorders: Hypotension. Potentially Fatal: Differentiation syndrome.
Patient Counseling Information
This drug may cause dizziness, if affected, do not drive or operate machinery. Females of reproductive potential must use effective contraception during therapy and for at least 6 months after stopping the treatment; an additional barrier method is recommended in women using hormonal contraceptives. Males with female partners of reproductive potential must use effective contraception during therapy and for at least 4 months after the last dose.
Confirm FLT3 mutation prior to initiation of therapy. Perform pregnancy tests in females of reproductive potential within 7 days before treatment initiation. Obtain blood chemistries including creatine phosphokinase before initiating treatment, then at least once weekly for the 1st month, then once every other week for the 2nd month, and once monthly thereafter. Monitor ECG before initiating treatment, on Days 8 and 15 of cycle 1, and before the start of the next 2 subsequent cycles. Correct hypokalaemia or hypomagnesaemia before and during treatment. Monitor adherence; signs and symptoms of differentiation syndrome, pancreatitis, and posterior reversible encephalopathy syndrome.
Decreased exposure and efficacy with P-gp and strong CYP3A4 inducers (e.g. phenytoin, rifampicin). Increased exposure with strong inhibitors of CYP3A4, P-gp, and/or breast cancer resistant protein (BCRP) (e.g. voriconazole, itraconazole, posaconazole, and clarithromycin). May reduce the effects of drugs that target 5-HT2B receptor or sigma nonspecific receptors (e.g. escitalopram, sertraline, fluoxetine).
St. John’s wort may decrease the plasma concentrations of gilteritinib.
Description: Gilteritinib is a tyrosine kinase inhibitor which inhibits FMS-like tyrosine kinase 3 (FLT3) receptor signalling and proliferation in cells exogenously expressing FLT3, including FLT3-ITD, tyrosine kinase domain mutations FLT3-D835Y and FLT3-ITD-D835Y. It also induces apoptosis in leukaemic cells expressing FLT3-ITD mutations. Onset: Inhibition of FLT3 phosphorylation: Within 24 hours after the 1st dose. Pharmacokinetics: Absorption: Time to peak plasma concentration: Approx 4-6 hours. Distribution: Extensively distributed to body tissues. Volume of distribution: 1,092 L (central); 1,100 L (peripheral). Plasma protein binding: Approx 90%, mainly to albumin. Metabolism: Metabolised in the liver mainly by CYP3A4 isoenzyme into M17 (via N-dealkylation and oxidation), M16 and M10 metabolites (both via N-dealkylation). Excretion: Mainly via faeces (64.5%); urine (approx 16.4% as unchanged drug and metabolites). Elimination half-life: 113 hours.
Store between 15-30°C. Protect from moisture, light, and humidity. Follow applicable procedures for receiving, handling, administration, and disposal.
L01EX13 - gilteritinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.
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