gilteritinib (Rx)

Brand and Other Names:Xospata
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Dosing & Uses

AdultPediatric

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
  • Information on FDA-approved tests for FLT3 mutation detection in AML is available at http://www.fda.gov/CompanionDiagnostics

Safey and efficacy not established

Next:

Interactions

Interaction Checker

and gilteritinib

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      Serious - Use Alternative

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            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 (111)

            • abametapir

              abametapir will increase the level or effect of gilteritinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • 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.

            • 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.

            • 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.

            • 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 (78)

            • 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.

            • 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.

            • 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)

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              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

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              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
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              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.

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              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

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              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

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              Images

              BRAND FORM. UNIT PRICE PILL IMAGE
              Xospata oral
              -
              40 mg tablet

              Copyright © 2010 First DataBank, Inc.

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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

              Adding plans allows you to compare formulary status to other drugs in the same class.

              To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

              Adding plans allows you to:

              • View the formulary and any restrictions for each plan.
              • Manage and view all your plans together – even plans in different states.
              • Compare formulary status to other drugs in the same class.
              • Access your plan list on any device – mobile or desktop.

              The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
              PA Prior Authorization
              Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
              QL Quantity Limits
              Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
              ST Step Therapy
              Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
              OR Other Restrictions
              Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.