Gilteritinib

Gilteritinib is a prescription medication indicated for the treatment of patients who have relapsed or refractory acute myeloid leukemia (AML) with FMS-like tyrosine kinase 3 (FLT3) mutation.

• Gilteritinib is available under the following different brand names: Xospata

Common side effects of Gilteritinib include:

• muscle or joint pain
• transaminase increase
• fatigue/malaise
• fever
• noninfectious diarrhea
• shortness of breath
• fluid retention/swelling
• rash
• pneumonia
• nausea
• inflammation of the mouth and lips
• cough
• headache
• low blood pressure (hypotension)
• dizziness
• vomiting

Serious side effects of Gilteritinib include:

• inflammation of the pancreas (pancreatitis)
• nausea/vomiting that doesn't stop, stomach/abdominal pain
• vision changes (such as blurred vision, decreased vision)
• mental/mood changes (such as confusion)

Rare side effects of Gilteritinib include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablet

• 40 mg

AML

Adult dosage

• 120 mg orally once a day
• Response may be delayed
• Continue for at least 6 months for clinical response or until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows:

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Gilteritinib has severe interactions with the following drugs:
  • dronedarone
  • saquinavir
  • thioridazine
• Gilteritinib has serious interactions with at least 116 other drugs
• Gilteritinib has moderate interactions with at least 79 other drugs
• Gilteritinib has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to gilteritinib or any of the excipients

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Gilteritinib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Gilteritinib?"

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 MRI; discontinue therapy in patients who develop PRES
• Associated with prolonged QT interval cardiac ventricular repolarization; in clinical trials, 1% of patients were found to have a QTc interval above 500 msec, and 7% of patients had an increase from baseline QTc above 60 msec; interrupt and reduced dosage in patients who have a QTcF above 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 were noted; interrupt and reduce dose in patients who develop pancreatitis
• Embryo-fetal harm may occur when administered to pregnant women
• Differentiation syndrome
  • Differentiation syndrome reported
  • 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 is suspected, initiate dexamethasone 10 mg IV every 12 hours (or an equivalent dose of an alternative oral or IV corticosteroid) and hemodynamic monitoring until improvement
  • Taper corticosteroids after resolution of symptoms and administer corticosteroids for a minimum of 3 days; symptoms of differentiation syndrome may recur with premature discontinuation of corticosteroid treatment
  • If severe signs and/or symptoms persist for more than 48 hours after initiation of corticosteroids, interrupt 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 and organic cation transporter 1
• 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 the 5HT2B receptor or sigma nonspecific receptor
  • Coadministration with drugs that target 5HT2B receptors or sigma nonspecific receptors (eg, escitalopram, fluoxetine, sertraline) may reduce the effects of these drugs
  • Avoid use of these drugs unless clinically necessary

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to pregnant women
• No data are available on use in pregnant women to inform a drug-associated risk for adverse developmental outcomes
• Advise pregnant women of potential fetal risks
• Pregnancy testing is recommended for women of reproductive potential within 7 days before initiating treatment
• Contraception
  • Females of reproductive potential: Use effective contraception during treatment and for 6 months and more after the last dose
  • Males: Males with partners of reproductive potential should use effective contraception during treatment and for 4 months and more
• Lactation
  • No data on the presence of gilteritinib and/or its metabolites in human milk, its effects on the breastfed child, or its effects on milk production
  • Following administration to lactating rats, milk concentrations of radioactivity were higher than radioactivity in maternal plasma at 4 and 24 hours 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 the last dose