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Vanflyta Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Tabs—14, 28
Manufacturer
Generic Availability
NO
Mechanism of Action
Quizartinib is a small molecule inhibitor of the receptor tyrosine kinase FLT3. Quizartinib and its active metabolite, AC886, inhibited FLT3 kinase activity, preventing autophosphorylation of the receptor, thereby inhibiting downstream FLT3 receptor signaling and blocking FLT3-ITD-dependent cell proliferation.
Vanflyta Indications
Indications
In combination with standard cytarabine and anthracycline induction, and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adults with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)-positive as detected by an FDA-approved test.
Limitations of Use
Not for maintenance monotherapy following allogeneic hematopoietic stem cell transplantation (HSCT).
Vanflyta Dosage and Administration
Adult
Confirm presence of FLT3-ITD mutation positivity. Swallow whole. Take at same time each day. Induction: 35.4mg once daily starting on Day 8 (for 7+3 regimen) for 2 weeks in each cycle (Days 8–21), for up to 2 cycles or until disease progression or unacceptable toxicity. For (5+2 regimen) as the second induction cycle, give dose on Days 6–19. Consolidation: 35.4mg once daily starting on Day 6 for 2 weeks in each cycle (Days 6–19), for up to 4 cycles or until disease progression or unacceptable toxicity. Maintenance: 26.5mg once daily Days 1–14 for the first cycle if QTcF ≤450ms; increase to 53mg once daily on Day 15 of first cycle if QTcF ≤450ms. Maintain at 26.5mg once daily if QTcF >500ms was seen during induction or conduction. Give once daily with no break between cycles for up to 36 cycles or until disease progression or unacceptable toxicity. Proceeding to HSCT: discontinue treatment 7 days before the start of a conditioning regimen. Dose modifications: see full labeling.
Children
Not established.
Vanflyta Contraindications
Contraindications
Severe hypokalemia. Severe hypomagnesemia. Long QT syndrome. History of ventricular arrhythmias or torsades de pointes.
Vanflyta Boxed Warnings
Boxed Warning
QT prolongation. Torsades de Pointes. Cardiac arrest.
Vanflyta Warnings/Precautions
Warnings/Precautions
Increased risk for QT prolongation, torsades de pointes, cardiac arrhythmias or arrest. Avoid in those who are at significant risk of developing torsades de pointes (including uncontrolled or significant cardiac disease, recent MI, heart failure, unstable angina, bradyarrhythmias, tachyarrhythmias, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism). Do not initiate if QTcF interval >450ms. Perform ECG and correct electrolyte abnormalities prior to initiation, during treatment, and as clinically indicated thereafter; monitor more frequently if at significant risk of developing QT prolongation and torsades de pointes, after dose increase, or vomiting/diarrhea occurs. Reduce dose if QTc >480–<500ms; interrupt and reduce dose if QTc >500ms. Permanently discontinue if recurrent QTc >500ms or QTc prolongation with signs of life-threatening arrhythmia develops. Severe renal or hepatic impairment: not studied. Embryo-fetal toxicity. Advise to use effective contraception during and for 7 months (females of reproductive potential) or 4 months (males w. female partners) after the last dose. Pregnancy: exclude status within 7 days prior to initiation. Nursing mothers: not recommended (during and for 1 month after the last dose).
REMS
Vanflyta Pharmacokinetics
Absorption
Absolute bioavailability: 71% (±7%). Time to peak concentration (median Tmax): ~4 hours (range 2–8 hours).
Distribution
Plasma protein bound: ≥99%. Volume of distribution (at steady state): 275 L.
Elimination
Fecal (76.3%), renal (1.64%). Half-life: 81±73 hours.
Vanflyta Interactions
Interactions
Potentiated by strong inhibitors; reduce dose. Concomitant strong or moderate CYP3A inducers; avoid. Concomitant other drugs known to prolong the QT interval (eg, azoles, ondansetron, granisetron, azithromycin, pentamidine, doxycycline, moxifloxacin, atovaquone, prochlorperazine, tacrolimus); monitor ECG more frequently.
Vanflyta Adverse Reactions
Adverse Reactions
Lab abnormalities (decreased lymphocytes, potassium, albumin, phosphorus, magnesium, calcium), increased alkaline phosphatase, increased creatine phosphokinase, febrile neutropenia, diarrhea, mucositis, nausea, abdominal pain, sepsis, neutropenia, headache, vomiting, upper respiratory tract infection, others.
Vanflyta Clinical Trials
See Literature
Vanflyta Note
Not Applicable
Vanflyta Patient Counseling
See Literature
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