phalopathy Syndrome
• Discontinue XOSPATA.
• QTc interval greater than 500 msec • Interrupt XOSPATA.
• Resume XOSPATA at 80 mg when QTc interval returns to within 30 msec ofbaseline or less than or equal to 480 msec.
• QTc interval increased by >30 msecon ECG on day 8 of cycle 1
• Confirm with ECG on day 9.
• If confirmed, consider dose reduction to 80 mg.
• Pancreatitis • Interrupt XOSPATA until pancreatitis is resolved.
• Resume XOSPATA at 80 mg.
• Other Grade 3* or higher toxicityconsidered related to treatment.
• Interrupt XOSPATA until toxicity resolves or improves to Grade 1*.
• Resume XOSPATA at 80 mg.
*Grade 1 is mild, Grade 2 is moderate, Grade 3 is serious, Grade 4 is life-threatening.
3 DOSAGE FORMS AND STRENGTHS
40 mg tablet: light yellow, round-shaped film-coated tablet debossed with the Astellas logo and ‘235’ on the same side.
4 CONTRAINDICATIONS
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients. Anaphylacticreactions have been observed in clinical trials [see Adverse Reactions (6) and Description (11)].
5 WARNINGS AND PRECAUTIONS
5.1 Posterior Reversible Encephalopathy Syndrome
There have been rare reports of posterior reversible encephalopathy syndrome (PRES) with symptoms including seizureand altered mental status with XOSPATA. Symptoms have resolved after discontinuation of XOSPATA. A diagnosis ofPRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). Discontinue XOSPATA inpatients who develop PRES [see Dosage and Administration (2.3) and Adverse Reactions (6.1)].
5.2 Prolonged QT Interval
XOSPATA has been associated with prolonged cardiac ventricular repolarization (QT interval). Of the 292 patientstreated with XOSPATA in the clinical trial, 1.4% were found to have a QTc interval greater than 500 msec and 7% ofpatients had an increase from baseline QTc greater than 60 msec. Perform electrocardiogram (ECG) prior to initiation oftreatment with gilteritinib, on days 8 and 15 of cycle 1, and prior to the start of the next two subsequent cycles. Interruptand reduce XOSPATA dosage in patients who have a QTcF >500 msec [see Dosage and Administration (2.3), AdverseReactions (6.1) and Clinical Pharmacology (12.2)].
Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct hypokalemia or hypomagnesemia priorto and during XOSPATA administration.
5.3 Pancreatitis
There have been rare reports of pancreatitis in patients receiving XOSPATA in clinical studies. eva luate patients whodevelop signs and symptoms of pancreatitis. Interrupt and reduce the dose of XOSPATA in patients who developpancreatitis [see Dosage and Administration (2.3)].
5.4 Embryo-Fetal Toxicity
Based on findings in animals and its mechanism of action, XOSPATA can cause embryo-fetal harm when administered toa pregnant woman. In animal reproduction studies, administration of gilteritinib to pregnant rats during organogenesiscaused embryo-fetal lethality, suppressed fetal growth and teratogenicity at maternal exposures (AUC24) approximately0.4 times the AUC24 in patients receiving the recommended dose. Advise females of reproductive potential to useeffective contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA.
Advise males with female partne |
