Dosing & Uses
Dosage Forms & Strengths
tablet
- 40mg
Acute Myeloid Leukemia
Indicated for treatment of patients who have relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation
120 mg PO qDay
Response may be delayed
Continue for at least 6 months for a clinical response or until disease progression or unacceptable toxicity
Dosage Modifications
Dosage modifications for adverse reactions
- Posterior reversible encephalopathy syndrome (PRES): Discontinue treatment
- QTc interval >500 msec: Interrupt treatment; resume at 80 mg when QTc interval returns to within 30 msec of baseline or ≤480 msec
- QTc interval increased by >30 msec on ECG on Day 8 of Cycle 1: Confirm ECG on Day 9; if confirmed, consider reducing dose to 80 mg
- Pancreatitis: Interrupt treatment until pancreatitis resolved; resume at 80 mg
- Other Grade ≥3 drug-related toxicity: Interrupt until toxicity resolves or improves to Grade 1; resume at 80 mg
-
Differentiation syndrome
- If suspected, administer systemic corticosteroids and initiate hemodynamic monitoring until symptoms resolve for at least 3 days
- Interrupt dose if severe signs and/or symptoms persist for >48 hr after initiation of corticosteroids
- Resume when signs and symptoms improve to Grade ≤2
Renal or hepatic impairment
- Mild or moderate ([CrCl 30-80 mL/min] or [Child-Pugh Class A or B]): No clinically meaningful effects on the pharmacokinetics of gilteritinib
- Severe ([CrCl <30 mL/min] or [Child-Pugh C]): Unknown
Dosing Considerations
Assess blood cell counts and chemistries prior to initiation, at least qWeek for the first month, once every other week for the second month, and once monthly thereafter
Perform ECG prior to initiation of treatment, on Days 8 and 15 of Cycle 1, and prior to the next 2 subsequent cycles
Patient selection
- Select patients based on presence of FLT3 mutation in blood or bone marrow by LeukoStrat CDx FLT3 Mutation Assay
- Information on FDA-approved tests for FLT3 mutation detection in AML is available at http://www.fda.gov/CompanionDiagnostics
Safey and efficacy not established
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (3)
- dronedarone
gilteritinib and dronedarone both increase QTc interval. Contraindicated.
- saquinavir
gilteritinib and saquinavir both increase QTc interval. Contraindicated.
- thioridazine
gilteritinib and thioridazine both increase QTc interval. Contraindicated.
Serious - Use Alternative (116)
- amiodarone
gilteritinib and amiodarone both increase QTc interval. Avoid or Use Alternate Drug.
- amisulpride
amisulpride and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug. ECG monitoring is recommended if coadministered.
- anagrelide
gilteritinib and anagrelide both increase QTc interval. Avoid or Use Alternate Drug.
- apalutamide
apalutamide will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- arsenic trioxide
gilteritinib and arsenic trioxide both increase QTc interval. Avoid or Use Alternate Drug.
- artemether
artemether and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- artemether/lumefantrine
artemether/lumefantrine and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine
gilteritinib and asenapine both increase QTc interval. Avoid or Use Alternate Drug.
- asenapine transdermal
asenapine transdermal and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- atazanavir
atazanavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- azithromycin
gilteritinib and azithromycin both increase QTc interval. Avoid or Use Alternate Drug.
- bedaquiline
bedaquiline and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine
gilteritinib and buprenorphine both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine buccal
buprenorphine buccal and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine subdermal implant
buprenorphine subdermal implant and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine transdermal
buprenorphine transdermal and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- buprenorphine, long-acting injection
buprenorphine, long-acting injection and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- carbamazepine
carbamazepine will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- ceritinib
ceritinib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- chloramphenicol
chloramphenicol will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- chloroquine
chloroquine and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- chlorpromazine
gilteritinib and chlorpromazine both increase QTc interval. Avoid or Use Alternate Drug.
- citalopram
gilteritinib will decrease the level or effect of citalopram by Other (see comment). Avoid or Use Alternate Drug. Coadministration of gilteritinib with drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary.
citalopram and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug. - clarithromycin
clarithromycin will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
gilteritinib and clarithromycin both increase QTc interval. Avoid or Use Alternate Drug. If coadministration necessary, monitor ECG - cobicistat
cobicistat will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- conivaptan
conivaptan will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- crizotinib
crizotinib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- darunavir
darunavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- desflurane
desflurane and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
gilteritinib and desflurane both increase QTc interval. Avoid or Use Alternate Drug. - disopyramide
gilteritinib and disopyramide both increase QTc interval. Avoid or Use Alternate Drug.
- dofetilide
gilteritinib and dofetilide both increase QTc interval. Avoid or Use Alternate Drug.
- droperidol
gilteritinib and droperidol both increase QTc interval. Avoid or Use Alternate Drug.
- encorafenib
encorafenib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- entrectinib
entrectinib and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- erdafitinib
erdafitinib will increase the level or effect of gilteritinib by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If coadministration unavoidable, separate administration by at least 6 hr before or after administration of P-gp substrates with narrow therapeutic index.
- eribulin
eribulin and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin base
gilteritinib and erythromycin base both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin ethylsuccinate
gilteritinib and erythromycin ethylsuccinate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin lactobionate
gilteritinib and erythromycin lactobionate both increase QTc interval. Avoid or Use Alternate Drug.
- erythromycin stearate
gilteritinib and erythromycin stearate both increase QTc interval. Avoid or Use Alternate Drug.
- escitalopram
gilteritinib will decrease the level or effect of escitalopram by Other (see comment). Avoid or Use Alternate Drug. Coadministration of gilteritinib with drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary.
gilteritinib and escitalopram both increase QTc interval. Avoid or Use Alternate Drug. - etrasimod
etrasimod, gilteritinib. Either increases effects of the other by immunosuppressive effects; risk of infection. Avoid or Use Alternate Drug. Risk of additive immune system effects with etrasimod has not been studied in combination with antineoplastic, immune-modulating, or noncorticosteroid immunosuppressive therapies. Avoid coadministration during and in the weeks following administration of etrasimod.
- fexinidazole
fexinidazole and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug. Avoid coadministration of fexinidazole with drugs known to block potassium channels or prolong QT interval.
- flecainide
gilteritinib and flecainide both increase QTc interval. Avoid or Use Alternate Drug.
- fluconazole
gilteritinib and fluconazole both increase QTc interval. Contraindicated.
- fluoxetine
gilteritinib will decrease the level or effect of fluoxetine by Other (see comment). Avoid or Use Alternate Drug. Coadministration of gilteritinib with drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary.
gilteritinib and fluoxetine both increase QTc interval. Avoid or Use Alternate Drug. - fluvoxamine
gilteritinib will increase the level or effect of fluvoxamine by Other (see comment). Avoid or Use Alternate Drug. Coadministrationwith drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary
gilteritinib and fluvoxamine both increase QTc interval. Avoid or Use Alternate Drug. - fosphenytoin
fosphenytoin will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- glasdegib
gilteritinib and glasdegib both increase QTc interval. Avoid or Use Alternate Drug.
- grapefruit
grapefruit will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- hydroxychloroquine sulfate
gilteritinib and hydroxychloroquine sulfate both increase QTc interval. Avoid or Use Alternate Drug.
- ibutilide
gilteritinib and ibutilide both increase QTc interval. Avoid or Use Alternate Drug.
- idelalisib
idelalisib will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- iloperidone
gilteritinib and iloperidone both increase QTc interval. Avoid or Use Alternate Drug.
- indinavir
indinavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- inotuzumab
gilteritinib and inotuzumab both increase QTc interval. Avoid or Use Alternate Drug.
- isoflurane
gilteritinib and isoflurane both increase QTc interval. Avoid or Use Alternate Drug.
- isoniazid
isoniazid will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- itraconazole
itraconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects.
gilteritinib and itraconazole both increase QTc interval. Avoid or Use Alternate Drug. - ivosidenib
gilteritinib and ivosidenib both decrease QTc interval. Avoid or Use Alternate Drug.
- ketoconazole
ketoconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- lapatinib
gilteritinib and lapatinib both increase QTc interval. Avoid or Use Alternate Drug.
- lefamulin
lefamulin and gilteritinib both increase QTc interval. Avoid or Use Alternate Drug.
- lenvatinib
gilteritinib and lenvatinib both increase QTc interval. Avoid or Use Alternate Drug.
- levoketoconazole
levoketoconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- lofexidine
gilteritinib and lofexidine both increase QTc interval. Avoid or Use Alternate Drug.
- lopinavir
lopinavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
gilteritinib and lopinavir both increase QTc interval. Avoid or Use Alternate Drug. - macimorelin
gilteritinib and macimorelin both increase QTc interval. Avoid or Use Alternate Drug.
- methadone
gilteritinib and methadone both increase QTc interval. Avoid or Use Alternate Drug.
- midostaurin
gilteritinib and midostaurin both increase QTc interval. Avoid or Use Alternate Drug.
- mifepristone
mifepristone will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
gilteritinib and mifepristone both increase QTc interval. Avoid or Use Alternate Drug. - mobocertinib
gilteritinib and mobocertinib both increase QTc interval. Avoid or Use Alternate Drug.
- moxifloxacin
gilteritinib and moxifloxacin both increase QTc interval. Avoid or Use Alternate Drug.
- nefazodone
nefazodone will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- nelfinavir
nelfinavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- nilotinib
gilteritinib and nilotinib both increase QTc interval. Avoid or Use Alternate Drug.
- ondansetron
gilteritinib and ondansetron both increase QTc interval. Avoid or Use Alternate Drug.
- osimertinib
gilteritinib and osimertinib both increase QTc interval. Avoid or Use Alternate Drug.
- oxaliplatin
gilteritinib and oxaliplatin both increase QTc interval. Avoid or Use Alternate Drug.
- ozanimod
gilteritinib and ozanimod both increase QTc interval. Avoid or Use Alternate Drug.
- paliperidone
gilteritinib and paliperidone both increase QTc interval. Avoid or Use Alternate Drug.
- panobinostat
gilteritinib and panobinostat both increase QTc interval. Avoid or Use Alternate Drug.
- paroxetine
gilteritinib will decrease the level or effect of paroxetine by Other (see comment). Avoid or Use Alternate Drug. Coadministration of gilteritinib with drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary.
gilteritinib and paroxetine both increase QTc interval. Avoid or Use Alternate Drug. - pazopanib
gilteritinib and pazopanib both increase QTc interval. Avoid or Use Alternate Drug.
- pentamidine
gilteritinib and pentamidine both increase QTc interval. Avoid or Use Alternate Drug.
- phenobarbital
phenobarbital will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- phenytoin
phenytoin will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- pimavanserin
gilteritinib and pimavanserin both increase QTc interval. Avoid or Use Alternate Drug.
- pimozide
gilteritinib and pimozide both increase QTc interval. Contraindicated.
- pitolisant
gilteritinib and pitolisant both increase QTc interval. Avoid or Use Alternate Drug.
- ponesimod
gilteritinib and ponesimod both increase QTc interval. Avoid or Use Alternate Drug.
- posaconazole
posaconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
gilteritinib and posaconazole both increase QTc interval. Avoid or Use Alternate Drug. - procainamide
gilteritinib and procainamide both increase QTc interval. Avoid or Use Alternate Drug.
- propafenone
gilteritinib and propafenone both increase QTc interval. Avoid or Use Alternate Drug.
- quetiapine
gilteritinib and quetiapine both increase QTc interval. Avoid or Use Alternate Drug.
- quinidine
gilteritinib and quinidine both increase QTc interval. Avoid or Use Alternate Drug.
- quinine
gilteritinib and quinine both increase QTc interval. Avoid or Use Alternate Drug.
- ribociclib
gilteritinib and ribociclib both increase QTc interval. Avoid or Use Alternate Drug.
- rifampin
rifampin will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- ritonavir
ritonavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- saquinavir
saquinavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- selpercatinib
gilteritinib and selpercatinib both increase QTc interval. Avoid or Use Alternate Drug.
- sertraline
gilteritinib will decrease the level or effect of sertraline by Other (see comment). Avoid or Use Alternate Drug. Coadministration of gilteritinib with drugs that inhibit 5HT2B or sigma nonspecific receptors. Avoid use of these drugs with gilteritinib unless coadministration is necessary.
- sevoflurane
gilteritinib and sevoflurane both increase QTc interval. Avoid or Use Alternate Drug.
- siponimod
gilteritinib and siponimod both increase QTc interval. Avoid or Use Alternate Drug.
- sorafenib
gilteritinib and sorafenib both increase QTc interval. Avoid or Use Alternate Drug.
- St John's Wort
St John's Wort will decrease the level or effect of gilteritinib by Other (see comment). Avoid or Use Alternate Drug. Gilteritinib is a P-gp and CYP3A4 substrates. Coadministration of gilteritinib with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure and efficacy.
- stiripentol
stiripentol will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- tetrabenazine
gilteritinib and tetrabenazine both increase QTc interval. Avoid or Use Alternate Drug.
- tipranavir
tipranavir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
- toremifene
gilteritinib and toremifene both increase QTc interval. Avoid or Use Alternate Drug.
- trazodone
gilteritinib and trazodone both increase QTc interval. Avoid or Use Alternate Drug.
- vandetanib
gilteritinib and vandetanib both increase QTc interval. Avoid or Use Alternate Drug.
- vemurafenib
gilteritinib and vemurafenib both increase QTc interval. Avoid or Use Alternate Drug.
- voriconazole
voriconazole will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Consider alternatives to any strong CYP3A4 inhibitor when coadministered with gilteritinib. If such a combination cannot be avoided, closely monitor for gilteritinib-related adverse effects. Interrupt and reduce gilteritinib dosage in patients with serious or life-threatening toxicity.
gilteritinib and voriconazole both increase QTc interval. Avoid or Use Alternate Drug. - ziprasidone
gilteritinib and ziprasidone both increase QTc interval. Avoid or Use Alternate Drug.
Monitor Closely (79)
- albuterol
albuterol and gilteritinib both increase QTc interval. Use Caution/Monitor.
- alfuzosin
alfuzosin and gilteritinib both increase QTc interval. Use Caution/Monitor.
- amitriptyline
gilteritinib and amitriptyline both increase QTc interval. Use Caution/Monitor.
- apomorphine
apomorphine and gilteritinib both increase QTc interval. Use Caution/Monitor.
- arformoterol
gilteritinib and arformoterol both increase QTc interval. Use Caution/Monitor.
- aripiprazole
aripiprazole and gilteritinib both increase QTc interval. Use Caution/Monitor.
- atomoxetine
atomoxetine and gilteritinib both increase QTc interval. Use Caution/Monitor.
- bosutinib
gilteritinib and bosutinib both increase QTc interval. Use Caution/Monitor.
- capecitabine
gilteritinib and capecitabine both increase QTc interval. Use Caution/Monitor.
- ciprofloxacin
gilteritinib and ciprofloxacin both increase QTc interval. Use Caution/Monitor.
- clofazimine
gilteritinib and clofazimine both increase QTc interval. Use Caution/Monitor.
- clomipramine
gilteritinib and clomipramine both increase QTc interval. Use Caution/Monitor.
- clozapine
clozapine and gilteritinib both increase QTc interval. Use Caution/Monitor.
- dasatinib
dasatinib and gilteritinib both increase QTc interval. Use Caution/Monitor.
- degarelix
degarelix and gilteritinib both increase QTc interval. Use Caution/Monitor.
- desipramine
gilteritinib and desipramine both increase QTc interval. Use Caution/Monitor.
- deutetrabenazine
deutetrabenazine and gilteritinib both increase QTc interval. Use Caution/Monitor. At the maximum recommended dose, deutetrabenazine does not prolong QT interval to a clinically relevant extent. Certain circumstances may increase risk of torsade de pointes and/or sudden death in association with drugs that prolong the QTc interval (eg, bradycardia, hypokalemia or hypomagnesemia, coadministration with other drugs that prolong QTc interval, presence of congenital QT prolongation).
- dolasetron
dolasetron and gilteritinib both increase QTc interval. Use Caution/Monitor.
- donepezil
donepezil and gilteritinib both increase QTc interval. Use Caution/Monitor.
- doxepin
doxepin and gilteritinib both increase QTc interval. Use Caution/Monitor.
- efavirenz
efavirenz and gilteritinib both increase QTc interval. Use Caution/Monitor.
- eliglustat
gilteritinib and eliglustat both increase QTc interval. Use Caution/Monitor.
- fingolimod
fingolimod and gilteritinib both increase QTc interval. Use Caution/Monitor.
- fluphenazine
gilteritinib and fluphenazine both increase QTc interval. Use Caution/Monitor.
- formoterol
gilteritinib and formoterol both increase QTc interval. Use Caution/Monitor.
- fostemsavir
gilteritinib and fostemsavir both increase QTc interval. Use Caution/Monitor. QTc prolongation reported with higher than recommended doses of fostemsavir.
- gadobenate
gadobenate and gilteritinib both increase QTc interval. Use Caution/Monitor.
- gemifloxacin
gemifloxacin and gilteritinib both increase QTc interval. Use Caution/Monitor.
- gemtuzumab
gilteritinib and gemtuzumab both increase QTc interval. Use Caution/Monitor.
- goserelin
gilteritinib and goserelin both increase QTc interval. Use Caution/Monitor.
- granisetron
gilteritinib and granisetron both increase QTc interval. Use Caution/Monitor.
- haloperidol
gilteritinib and haloperidol both increase QTc interval. Use Caution/Monitor.
- histrelin
gilteritinib and histrelin both increase QTc interval. Use Caution/Monitor.
- hydroxyzine
gilteritinib and hydroxyzine both increase QTc interval. Use Caution/Monitor.
- imipramine
gilteritinib and imipramine both increase QTc interval. Use Caution/Monitor.
- indacaterol, inhaled
gilteritinib and indacaterol, inhaled both increase QTc interval. Use Caution/Monitor.
- leuprolide
gilteritinib and leuprolide both increase QTc interval. Use Caution/Monitor.
- levalbuterol
gilteritinib and levalbuterol both increase QTc interval. Use Caution/Monitor.
- levofloxacin
gilteritinib and levofloxacin both increase QTc interval. Use Caution/Monitor.
- lithium
gilteritinib and lithium both increase QTc interval. Use Caution/Monitor.
- loperamide
gilteritinib and loperamide both increase QTc interval. Use Caution/Monitor.
- maprotiline
gilteritinib and maprotiline both increase QTc interval. Use Caution/Monitor.
- mefloquine
gilteritinib and mefloquine both increase QTc interval. Use Caution/Monitor.
- mirtazapine
gilteritinib and mirtazapine both increase QTc interval. Use Caution/Monitor.
- nortriptyline
gilteritinib and nortriptyline both increase QTc interval. Use Caution/Monitor.
- octreotide
gilteritinib and octreotide both increase QTc interval. Use Caution/Monitor.
- ofloxacin
gilteritinib and ofloxacin both increase QTc interval. Use Caution/Monitor.
- olanzapine
gilteritinib and olanzapine both increase QTc interval. Use Caution/Monitor. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances
- olodaterol inhaled
gilteritinib and olodaterol inhaled both increase QTc interval. Use Caution/Monitor.
- osilodrostat
gilteritinib and osilodrostat both increase QTc interval. Use Caution/Monitor. Dose dependent QT prolongation - avoid drugs known to prolong the QT interval
- pasireotide
gilteritinib and pasireotide both increase QTc interval. Use Caution/Monitor.
- perphenazine
gilteritinib and perphenazine both increase QTc interval. Use Caution/Monitor.
- primaquine
gilteritinib and primaquine both increase QTc interval. Use Caution/Monitor.
- prochlorperazine
gilteritinib and prochlorperazine both decrease QTc interval. Use Caution/Monitor.
- promethazine
gilteritinib and promethazine both decrease QTc interval. Use Caution/Monitor.
- protriptyline
gilteritinib and protriptyline both increase QTc interval. Use Caution/Monitor.
- ranolazine
gilteritinib and ranolazine both increase QTc interval. Use Caution/Monitor.
- rilpivirine
gilteritinib and rilpivirine both increase QTc interval. Use Caution/Monitor.
- risperidone
gilteritinib and risperidone both increase QTc interval. Use Caution/Monitor.
- romidepsin
gilteritinib and romidepsin both increase QTc interval. Use Caution/Monitor.
- salmeterol
gilteritinib and salmeterol both increase QTc interval. Use Caution/Monitor.
- sertraline
gilteritinib and sertraline both increase QTc interval. Use Caution/Monitor.
- siponimod
siponimod and gilteritinib both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.
- solifenacin
gilteritinib and solifenacin both increase QTc interval. Use Caution/Monitor.
- sotalol
gilteritinib and sotalol both increase QTc interval. Use Caution/Monitor.
- sunitinib
gilteritinib and sunitinib both increase QTc interval. Use Caution/Monitor.
- tacrolimus
gilteritinib and tacrolimus both increase QTc interval. Use Caution/Monitor.
- telavancin
gilteritinib and telavancin both increase QTc interval. Use Caution/Monitor.
- triclabendazole
gilteritinib and triclabendazole both increase QTc interval. Use Caution/Monitor.
- trifluoperazine
gilteritinib and trifluoperazine both decrease QTc interval. Use Caution/Monitor.
- trimipramine
gilteritinib and trimipramine both increase QTc interval. Use Caution/Monitor.
- triptorelin
gilteritinib and triptorelin both increase QTc interval. Use Caution/Monitor.
- umeclidinium bromide/vilanterol inhaled
gilteritinib and umeclidinium bromide/vilanterol inhaled both decrease QTc interval. Use Caution/Monitor.
- valbenazine
valbenazine and gilteritinib both increase QTc interval. Use Caution/Monitor.
- vardenafil
gilteritinib and vardenafil both increase QTc interval. Use Caution/Monitor.
- venlafaxine
gilteritinib and venlafaxine both decrease QTc interval. Use Caution/Monitor.
- vilanterol/fluticasone furoate inhaled
gilteritinib and vilanterol/fluticasone furoate inhaled both increase QTc interval. Use Caution/Monitor.
- voclosporin
gilteritinib and voclosporin both increase QTc interval. Use Caution/Monitor.
- vorinostat
gilteritinib and vorinostat both increase QTc interval. Use Caution/Monitor.
Minor (0)
Adverse Effects
>10%
Myalgia/arthralgia (42%)
Increased transaminases (41%)
Fatigue/malaise (40%)
Fever (35%)
Dyspnea (34%)
Edema (34%)
Noninfectious diarrhea (34%)
Rash (30%)
Pneumonia (30%)
Constipation (27%)
Nausea (27%)
Stomatitis (26%)
Cough (25%)
Pneumonia, Grade 3 or 4 (23%)
Hypotension (21%)
Headache (21%)
Dizziness (20%)
Vomiting (20%)
Renal impairment (19%)
Abdominal pain (17%)
Increased transaminases, Grade 3 or 4 (16%)
Decreased appetite (15%)
Sepsis (15%)
Insomnia (14%)
Sepsis, Grade 3 or 4 (14%)
Dyspnea, Grade 3 or 4 (12%)
Dysgeusia (11%)
Increased bilirubin (11%)
1-10%
Hypertension (10%)
Hypotension, Grade 3 or 4 (7%)
Hypertension, Grade 3 or 4 (6%)
Myalgia/arthralgia, Grade 3 or 4 (5%)
Increased bilirubin, Grade 3 or 4 (5%)
Fever, Grade 3 or 4 (5%)
Fatigue/malaise, Grade 3 or 4 (5%)
Renal impairment, Grade 3 or 4 (4%)
Stomatitis, Grade 3 or 4 (4%)
Noninfectious diarrhea, Grade 3 or 4 (3%)
Rash, Grade 3 or 4 (3%)
Edema, Grade 3 or 4 (2%)
Decreased appetite, Grade 3 or 4 (2%)
Abdominal pain, Grade 3 or 4 (2%)
Headache, Grade 3 or 4 (1%)
Nausea, Grade 3 or 4 (1%)
<1%
Constipation, Grade 3 or 4
Insomnia, Grade 3 or 4
Dizziness, Grade 3 or 4
Cough, Grade 3 or 4
Postmarketing Reports
Differentiation syndrome
Warnings
Black Box Warnings
Differentiation syndrome
- Symptoms of differentiation syndrome may occur, which can be fatal or life-threatening
- Symptoms may include fever, dyspnea, hypoxia, pulmonary infiltrates, pleural or pericardial effusions, rapid weight gain or peripheral edema, hypotension, or renal dysfunction
- If differentiation syndrome suspected, initiate corticosteroid therapy and hemodynamic monitoring until symptom resolution
Contraindications
Hypersensitivity to gilteritinib or any of the excipients
Cautions
Rare reports of posterior reversible encephalopathy syndrome (PRES) with symptoms including seizure and altered mental status; symptoms resolved after discontinuing treatment; a diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI); discontinue therapy in patients who develop PRES
Associated with prolonged QT interval cardiac ventricular repolarization; in clinical trials, 1% were found to have a QTc interval >500 msec and 7% of patients had an increase from baseline QTc >60 msec; interrupt and reduce dosage in patients who have a QTcF >500 msec
Hypokalemia or hypomagnesemia may increase QT prolongation risk; correct electrolyte abnormalities before initiating and during administration
In clinical trials, rare reports of pancreatitis noted; interrupt and reduce dose in patients who develop pancreatitis
Embryo-fetal harm may occur when administered to pregnant women (see Pregnancy)
Differentiation syndrome
- Differentiation syndrome reported (see Black Box Warnings)
- Associated with rapid proliferation and differentiation of myeloid cells and may be life-threatening or fatal if not treated
- May occur as early as 1 day and up to 82 days after initiation of therapy and has been observed with or without concomitant leukocytosis
- If differentiation syndrome 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 therapy until signs and symptoms are no longer severe
Drug interactions overview
- Gilteritinib is a CYP3A and P-gp substrate; it potentially inhibits breast cancer resistance protein (BCRP) and organic cation transporter 1 (OCT1) transporter
-
Combined P-gp and strong CYP3A inducers
- Coadministration with a combined P-gp and strong CYP3A inducer decreases gilteritinib exposure which may decrease efficacy
- Avoid use with combined P-gp and strong CYP3A inducers
-
Strong CYP3A inhibitors
- Coadministration with a strong CYP3A inhibitor increases gilteritinib exposure
- Consider alternative therapies that are not strong CYP3A inhibitors; if concomitant use is necessary, closely monitor for adverse reactions of gilteritinib
- Interrupt and reduce dose in patients with serious or life-threatening toxicity
-
Drugs that target 5HT2B receptor or sigma nonspecific receptor
- Coadministration with drugs that target 5HT2B receptors or sigma nonspecific receptors (eg, escitalopram, fluoxetine, sertraline) may reduce effects of these drugs
- Avoid use of these drugs unless clinically necessary
Pregnancy
Pregnancy
Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to pregnant women
No data available on use in pregnant women to inform a drug-associated risk of adverse developmental outcomes
Advise pregnant women of potential fetal risks
Pregnancy testing recommended for females of reproductive potential within 7 days before initiating treatment
Animal studies
- In animal reproduction studies, administration to pregnant rats during organogenesis caused adverse developmental outcomes including embryo-fetal lethality, suppressed fetal growth, and teratogenicity at maternal exposures ~0.4 times the AUC in patients receiving the recommended dose
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for ≥6 months after last dose
- Males: Males with partners of reproductive potential should use effective contraception during treatment and for ≥4 months
Lactation
No data on presence of gilteritinib and/or its metabolites in human milk, effects on the breastfed child, or effects on milk production
Following administration to lactating rats, milk concentrations of radioactivity were higher than radioactivity in maternal plasma at 4 and 24 hr post-dose
In animal studies, gilteritinib and/or its metabolite(s) were distributed to tissues in infant rats via the milk
Advise lactating women not to breastfeed during treatment and for 2 months after last dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Small molecule that inhibits multiple receptor tyrosine kinases, including FMS-like tyrosine kinase 3 (FLT3)
Demonstrates ability to inhibit FLT3 receptor signaling and proliferation in cells exogenously expressing FLT3 including FLT3-ITD, tyrosine kinase domain mutations (TKD) FLT3-D835Y and FLT3-ITD-D835Y, and induces apoptosis in leukemic cells expressing FLT3-ITD
Absorption
Peak plasma concentration (steady-state): 374 ng/mL
Peak plasma time (fasted state): 4-6 hr
AUC: 6943 ng·hr/mL
Steady-state plasma levels reached: Within 15 days
Effect of food (single 40-mg dose in healthy adults)
- Peak plasma concentration decreased by 26% and AUC decreased by <10% when coadministered with a high-fat meal compared to a fasted state
- Median peak plasma time delayed by 2 hr when administered with a high-fat meal
Distribution
Vd: 1092 L (central); 1100 L (peripheral)
Protein bound: ~94%
Metabolism
Primarily metabolized via CYP3A4
At steady state, primary metabolites include M17 (formed via N-dealkylation and oxidation), M16 and M10 (both formed via N-dealkylation)
None of these metabolites exceeded 10% of overall parent exposure
Elimination
Half-life: 113 hr
Clearance: 14.85 L/hr
Excretion (single-dose): Feces (64.5%)
Excretion (total-dose): Urine (16.4% [unchanged drug and metabolites])
Pharmacogenomics
Patient selection are based on presence of FLT3 mutation in blood or bone marrow
Administration
Oral Administration
Administer with or without food
Swallow whole; do not break or crush
Administer at same time each day
Missed dose
- Administer as soon as possible on the same day, and at least 12 hr prior to next scheduled dose; resume normal schedule the following day
- Do not administer 2 doses within 12 hr
Storage
Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)
Keep in original container
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Xospata oral - | 40 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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