Genetic Implications:
Pronunciation:
gil-te-ri-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
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.
Therapeutic Effect(s):
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)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | unknown | 4–6 hr | 24 hr |
Contraindicated in:
Use Cautiously in:
CV: hypotension, peripheral edema, QT interval prolongation
Derm: rash
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
Metabolic: hypertriglyceridemia
MS: arthralgia, myalgia, ↑ creatine kinase
Neuro: neuropathy, POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES), dizziness, fatigue, headache, insomnia
Resp: cough, dyspnea
Misc: fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
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.
Lab Test Considerations:
Obtain a negative pregnancy test within 7 days before starting therapy.
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.
Improved survival in AML.