Important Safety Information
XOSPATA is contraindicated in patients with hypersensitivity to gilteritinib or any of the excipients.
Anaphylactic reactions have been observed in clinical trials.
Warnings and Precautions
Differentiation Syndrome (See BOXED WARNING) 3% of 319
patients treated with XOSPATA in the clinical trials experienced 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 of differentiation syndrome in patients treated with
XOSPATA included fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid
weight gain, peripheral edema, rash, and renal dysfunction. Some cases had concomitant acute febrile
neutrophilic dermatosis. Differentiation syndrome occurred as early as 2 days and up to 75 days after
XOSPATA initiation and has been observed with or without concomitant leukocytosis. If differentiation
syndrome is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an
alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement. Taper corticosteroids
after resolution of symptoms and administer corticosteroids for a minimum of 3 days. Symptoms of
differentiation syndrome may recur with premature discontinuation of corticosteroid treatment. If severe
signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt XOSPATA
until signs and symptoms are no longer severe.
Posterior Reversible Encephalopathy Syndrome (PRES) 1% of 319
patients treated with XOSPATA in the clinical trials experienced posterior reversible encephalopathy
syndrome (PRES) with symptoms including seizure and altered mental status. Symptoms have resolved after
discontinuation of XOSPATA. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic
resonance imaging (MRI). Discontinue XOSPATA in patients who develop PRES.
Prolonged QT Interval XOSPATA has been associated with
prolonged cardiac ventricular repolarization (QT interval). 1% of the 317 patients with a post-baseline QTc
measurement on treatment with XOSPATA in the clinical trial were found to have a QTc interval greater than
500 msec and 7% of patients had an increase from baseline QTc greater than 60 msec. Perform
electrocardiogram (ECG) prior to initiation of treatment with XOSPATA, on days 8 and 15 of cycle 1, and
prior to the start of the next two subsequent cycles. Interrupt and reduce XOSPATA dosage in patients who
have a QTcF >500 msec. Hypokalemia or hypomagnesemia may increase the QT prolongation risk. Correct
hypokalemia or hypomagnesemia prior to and during XOSPATA administration.
Pancreatitis 4% of 319 patients treated with XOSPATA in the
clinical trials experienced pancreatitis. Evaluate patients who develop signs and symptoms of pancreatitis.
Interrupt and reduce the dose of XOSPATA in patients who develop pancreatitis.
Embryo-Fetal Toxicity XOSPATA can cause embryo-fetal harm
when administered to a pregnant woman. Advise females of reproductive potential to use effective
contraception during treatment with XOSPATA and for at least 6 months after the last dose of XOSPATA. Advise
males with female partners of reproductive potential to use effective contraception during treatment with
XOSPATA and for at least 4 months after the last dose of XOSPATA. Pregnant women, patients becoming pregnant
while receiving XOSPATA or male patients with pregnant female partners should be apprised of the potential
risk to the fetus.
Fatal adverse reactions occurred in 2% of patients receiving XOSPATA. These were cardiac arrest (1%) and
one case each of differentiation syndrome and pancreatitis. The most frequent (≥5%) nonhematological serious
adverse reactions reported in patients were fever (13%), dyspnea (9%), renal impairment (8%), transaminase
increased (6%) and noninfectious diarrhea (5%).
7% discontinued XOSPATA treatment permanently due to an adverse reaction. The most common (>1%) adverse
reactions leading to discontinuation were aspartate aminotransferase increased (2%) and alanine
aminotransferase increased (2%).
The most frequent (≥5%) grade ≥3 nonhematological adverse reactions reported in patients were transaminase
increased (21%), dyspnea (12%), hypotension (7%), mucositis (7%), myalgia/arthralgia (7%), and
Other clinically significant adverse reactions occurring in ≤10% of patients included: electrocardiogram QT
prolonged (9%), hypersensitivity (8%), pancreatitis (5%), cardiac failure (4%), pericardial effusion (4%),
acute febrile neutrophilic dermatosis (3%), differentiation syndrome (3%), pericarditis/myocarditis (2%),
large intestine perforation (1%), and posterior reversible encephalopathy syndrome (1%).
Lab Abnormalities Shifts to grades 3-4 nonhematologic
laboratory abnormalities in XOSPATA treated patients included phosphate decreased (14%), alanine
aminotransferase increased (13%), sodium decreased (12%), aspartate aminotransferase increased (10%),
calcium decreased (6%), creatine kinase increased (6%), triglycerides increased (6%), creatinine increased
(3%), and alkaline phosphatase increased (2%).
Combined P-gp and Strong CYP3A Inducers Concomitant use of
XOSPATA with a combined P-gp and strong CYP3A inducer decreases XOSPATA exposure which may decrease XOSPATA
efficacy. Avoid concomitant use of XOSPATA with combined P-gp and strong CYP3A inducers.
Strong CYP3A inhibitors Concomitant use of XOSPATA with a
strong CYP3A inhibitor increases XOSPATA exposure. Consider alternative therapies that are not strong CYP3A
inhibitors. If the concomitant use of these inhibitors is considered essential for the care of the patient,
monitor patient more frequently for XOSPATA adverse reactions. Interrupt and reduce XOSPATA dosage in
patients with serious or life-threatening toxicity.
Drugs that Target 5HT2B Receptor or Sigma Nonspecific
Receptor Concomitant use of XOSPATA may reduce the effects of drugs that target the 5HT2B
receptor or the sigma nonspecific receptor (e.g., escitalopram, fluoxetine, sertraline). Avoid concomitant
use of these drugs with XOSPATA unless their use is considered essential for the care of the patient.
Lactation Advise women not to breastfeed during treatment
with XOSPATA and for 2 months after the last dose.
Please see Full Prescribing Information including BOXED WARNING for additional safety