Relapsed or refractory acute myeloid leukemia (AML) with a FMS-like tyrosine kinase 3 (FLT3) mutation.
Inhibits FLT3 receptor signaling and cell proliferation, and induces apoptosis in leukemic cells expressing FLT3–ITD.
Improved survival in AML.
Absorption: Absorption ↓ and delayed with high-fat food.
Distribution: Extensively distributed to tissues.
Metabolism and Excretion: Primarily metabolized via the liver by the CYP3A4 isoenzyme. Primarily excreted in the feces (64.5%), 16.4% excreted in urine.
Half-life: 113 hr.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||4–6 hr||24 hr|
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Electrolyte abnormalities
- Rep: Women of reproductive potential and men with female partners of reproductive potential;
- Pedi: Safety and effectiveness not established in children.
Adverse Reactions/Side Effects
CV: hypotension, peripheral edema, QT interval prolongation
F and E: hypocalcemia, hyponatremia, hypophosphatemia
GI: PANCREATITIS, abdominal pain, constipation, ↑ liver enzymes, metallic taste, mucositis, nausea, vomiting, diarrhea
GU: renal impairment
Hemat: DIFFERENTIATION SYNDROME
MS: arthralgia, myalgia, ↑ creatine kinase
Neuro: neuropathy, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), dizziness, fatigue, headache, insomnia
Resp: cough, dyspnea
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Combined P-glycoprotein and strong CYP3A inducers may ↓ levels and effectiveness; avoid concurrent use.
- Strong CYP3A inhibitors may ↑ levels and risk of toxicity; consider an alternative therapy that does not inhibit CYP3A.
- May ↓ levels of escitalopram, fluoxetine, and sertraline ; avoid concurrent use.
PO (Adults): 120 mg once daily; continue treatment for ≥6 mo (provided that disease progression and/or unacceptable toxicity do not occur) to determine clinical response.
Tablets: 40 mg
Monitor for signs and symptoms of differentiation syndrome (fever, dyspnea, pleural effusion, pericardial effusion, pulmonary edema, hypotension, rapid weight gain, peripheral edema, rash, renal dysfunction) during therapy. If suspected, administer systemic corticosteroids (dexamethasone 10 mg IV every 12 hrs or equivalent) and begin hemodynamic monitoring until symptom resolution. Administer corticosteroids for at least 3 days and taper after symptoms resolve. If severe signs and symptoms persist for >48 hrs after starting corticosteroids, hold gilteritinib until signs and symptoms are no longer severe.
Monitor for signs and symptoms of posterior reversible encephalopathy syndrome (PRES) (impaired consciousness, convulsions, visual disturbances including blindness, loss of motor function, movement disorders, psychiatric disturbances, papilledema, visual impairment). Discontinue therapy if PRES develops. Usually reversible with discontinuation of gilteritinib.
Assess ECG before starting, on days 8 and 15 of cycle 1, and before starting next two subsequent cycles. If QTc >500 msec, hold dose and reduce to 80 mg when QTc interval returns to within 30 msec of baseline or ≤480 msec. If QTc increased by >30 msec on ECG on day 8 of cycle 1, confirm with ECG on day 9. If confirmed, consider dose reduction to 80 mg. Hypokalemia and hypomagnesemia may increase risk or QT prolongation; monitor levels and correct before and during therapy.
- Monitor for signs and symptoms of pancreatitis (severe abdominal pain) during therapy. If symptoms occur, hold gilteritinib and resume at 80 mg when symptoms resolved.
Lab Test Considerations:
Obtain a negative pregnancy test within 7 days before starting therapy.
- Selection of patients is based on the presence of FLT3 mutations in blood or bone marrow. FDA-approved tests for detection of FLT3 mutation are available at http://www.fda.gov/CompanionDiagnostics.
- Assess CBC and blood chemistries, including creatine kinase, before starting gilteritinib, at least once weekly for 1st mo, once every other wk for 2nd mo, and monthly for duration of therapy.
- Deficient knowledge, related to medication regimen (Patient/Family/Teaching)
- PO Administer once daily at the same time each day without regard to food. Swallow tablet whole; do not crush, break, or chew.
- Instruct patient to take gilteritinib as directed. Take missed doses as soon as remembered on the same day and at least 12 hrs before next scheduled dose; do not double doses. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional immediately if signs and symptoms of differentiation syndrome fever, cough, dizziness or lightheadedness, rapid weight gain, trouble breathing, swelling of arms or legs, rash, decreased urination), PRES (headache, decreased alertness, confusion, reduced eyesight, blurred vision, other visual problems), QT prolongation (dizziness, lightheadedness, feeling faint), or pancreatitis occur.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Rep: May be teratogenic. Advise females of reproductive potential to use effective contraception during and for at least 6 mo after last dose and to avoid breastfeeding during and for at least 2 mo after last dose of gilteritinib. Advise males with female partners of reproductive potential to use effective contraception during and for at least 4 mo after last dose.
Improved survival in AML.