XOSPATA

What it is

XOSPATA contains gilteritinib fumarate, with each film-coated tablet containing 44.2 mg gilteritinib fumarate (corresponding to 40 mg gilteritinib). Gilteritinib fumarate is a FMS-like tyrosine kinase 3 (FLT3) and AXL inhibitor. This medicinal product is subject to additional monitoring in Australia to allow quick identification of new safety information.

Approved indications

— Treatment of adult patients who have relapsed or refractory acute myeloid leukaemia (AML) with a FLT3 mutation.

Dosing overview

The recommended starting dose of XOSPATA is 120 mg (three 40 mg tablets) once daily. In the absence of a response after 4 weeks of treatment, the dose can be increased to 200 mg (five 40 mg tablets) once daily, if tolerated or clinically warranted. Continuation of treatment at the prescribed dose for up to 6 months should be considered to allow time for a clinical response. XOSPATA can be taken with or without food and the tablets should be swallowed whole with water and should not be broken or crushed.

Key safety warnings

XOSPATA has been associated with differentiation syndrome, which is associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated. Symptoms and other clinical findings of differentiation syndrome include fever, dyspnoea, pleural effusion, pericardial effusion, pulmonary oedema, hypotension, rapid weight gain, peripheral oedema, rash, and renal dysfunction, and if suspected, corticosteroid therapy should be initiated along with hemodynamic monitoring until symptom resolution. There have been reports of posterior reversible encephalopathy syndrome (PRES) in patients receiving XOSPATA, which is a rare, reversible, neurological disorder that can present with rapidly evolving symptoms including seizure, headache, confusion, visual and neurological disturbances, with or without associated hypertension and altered mental status. Gilteritinib has been associated with prolonged cardiac ventricular repolarisation (QT interval), which can be observed in the first three months of treatment with XOSPATA. Hypokalaemia or hypomagnesaemia may increase the QT prolongation risk and should therefore be corrected prior to and during XOSPATA treatment. There have been reports of pancreatitis, and patients who develop signs and symptoms suggestive of pancreatitis should be evaluated and monitored.

Contraindications

XOSPATA is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients. Anaphylactic reactions have been observed in clinical trials.

PBS listing

XOSPATA 40 mg tablets are listed on the PBS with 2 items, authority required restriction, and an ex-manufacturer price of A$24983.00.

Regulatory history

XOSPATA (gilteritinib 40 mg film-coated tablets) was first registered on the ARTG on 2 April 2020. An AusPAR (Australian Public Assessment Report) was issued on 26 March 2020 for the indication of relapsed or refractory acute myeloid leukaemia with a FLT3 mutation. The PBAC recommended against listing in November 2021 for acute myeloid leukaemia.