Gilteritinib (XOSPATA)

Acute myeloid leukemia

Acute myeloid leukemia

• Oral: 120mg daily continuously until disease progression or unacceptable toxicity
  • In the absence of clinical response, dose may be increased to 200mg daily continuously
• Please refer to specific protocol for more information on increasing dose

Available as 40 mg film-coated tablets. Tablets should NOT be crushed or broken. Store at room temperature.

FLT3 inhibitor

Take with or without food

If a dose is missed, patients should be instructed to take it as soon as they can if it is within 12 hours of the missed dose. If it is over 12 hours since the missed dose, patients should skip the missed dose and resume with the next scheduled dose.

Common: Fatigue, ALT increase, AST increase, Hypotension.

Less Common: Febrile neutropenia, Thrombocytopenia, Cardiac failure, Large intestine perforation, Pancreatitis, Pneumonia, Septic shock, QTc prolongation, Posterior reversible encephalopathy syndrome, Acute kidney injury, Differentiation syndrome , Eye disorders including blurred vision, retinal hemorrhage, and cataract.

The adverse effects listed above are not exhaustive. Please refer to the relevant product monograph for full details.

Baseline before treatment: CBC & differential, platelet, sodium, potassium, calcium, magnesium, phosphate, urea, creatinine, bilirubin (total and direct), GGT, alkaline phosphatase, LDH, ALT, albumin, creatine kinase, lipase, serum HCG (for women of childbearing potential).

During treatment:

• Cycle 1 - weekly: CBC & differential, platelet, sodium, potassium, calcium, magnesium, phosphate, urea, creatinine, bilirubin (total and direct), GGT, alkaline phosphatase, LDH, ALT, albumin, creatine kinase.
• Cycle 2 - prior to cycle and on day 15: CBC & differential, platelet, sodium, potassium, calcium, magnesium, phosphate, urea, creatinine, bilirubin (total and direct), GGT, alkaline phosphatase, LDH, ALT, albumin, creatine kinase.
• Cycle 3 onwards – prior to each cycle: CBC & differential, platelet, sodium, potassium, calcium, magnesium, phosphate, urea, creatinine, bilirubin (total and direct), GGT, alkaline phosphatase, LDH, ALT, albumin, creatine kinase.

Note: Bone marrow aspirate and biopsy is recommended on cycle 2 day 1 to assess response. In patients who are not in a complete remission (CR) at this time, this should be repeated every 1-2 months to assess remission status until CR is documented.

Note: Lipase should be added to monitoring if clinically indicated.

QTc should be monitored as follows:

• Cycle 1: Baseline, Day 8 and 15
• Cycle 2 and 3: before each cycle
• Cycle 4 onward: as clinically indicated

• May increase the risk for QT interval prolongation. Avoid concurrent therapy with drugs associated with QTc prolongation and/or Torsades de pointes, if possible. If unavoidable, monitor for QT prolongation or cardiac arrhythmias.
• This drug can impact or be impacted by metabolic enzymes for absorption and excretion. Many drugs can also affect or be affected by these enzymes, so please consult with pharmacy to assess for interactions.
• Current drug interaction databases should be consulted for more information.

• Avoid in pregnancy and lactation.
• Differentiation syndrome has been reported in patients treated with Gilteritinib. Symptoms and clinical findings may include fever, dyspnea, pleural effusion, pericardial effusion, pulmonary infiltrate, hypotension, rapid weight gain, peripheral edema, rash, and renal dysfunction. Differentiation syndrome can be fatal if not treated. If differentiation syndrome is suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution.
• Posterior reversible encephalopathy syndrome (PRES) has been reported.  Symptoms include seizure and altered mental status. Discontinue Gilteritinib in patients who develop PRES.
• Pancreatitis has been reported with Gilteritinib. Evaluate and monitor patients who develop signs and symptoms suggestive of pancreatitis.

BC Cancer. BC Cancer Drug Manual. Gilteritinib.  Vancouver, British Columbia: BC Cancer Agency. Available at: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Gilteritinib_monograph.pdf .Updated September 1, 2021.  Accessed February 2, 2024.

Lexicomp. Gilteritinib Monograph. In: Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc. Available at: https://online-lexi-com.qe2a-proxy.mun.ca/lco/action/doc/retrieve/docid/patch_f/6732257?cesid=ahBgJSl9p1q&searchUrl=%2Flco%2Faction%2Fsearch%3Fq%3DGilteritinib%26t%3Dname%26acs%3Dfalse%26acq%3DGilteritinib . Updated January 24, 2024. Accessed February 2, 2024.

Cancer Care Ontario. Gilteritinib Monograph. Drug Formulary. Toronto, Ontario: Cancer Care Ontario. Available at: https://www.cancercareontario.ca/en/drugformulary/drugs/monograph/71126. Updated July 2023. Accessed January 22, 2024.

Astellas Pharma Canada Inc. XOSPATA® Product Monograph. Markham, Ontario. Updated January 4, 2022.