Version May 2024
Quizartinib prolongs the QT interval in a dose- and concentration-related manner. Prior to quizartinib administration and periodically, monitor for hypokalemia or hypomagnesemia, and correct deficiencies. Perform ECGs to monitor the QTc at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter. Torsades de pointes and cardiac arrest have occurred in patients receiving quizartinib. Do not administer quizartinib to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome. Do not initiate treatment with quizartinib or escalate the quizartinib dose if the QTcF is >450 msec. Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required. Reduce the quizartinib dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure.
Because of the risk of QT prolongation, quizartinib is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Vanflyta REMS.
Note: Do not initiate treatment with quizartinib if the QTc interval (corrected by Fridericia formula [QTcF]) is >450 msec. Correct electrolyte abnormalities prior to initiation of treatment. Do not use quizartinib in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or history of ventricular arrhythmias or torsades de pointes.
Acute myeloid leukemia, newly diagnosed, FLT3-ITD-mutated:
Note: A treatment course consists of up to 2 induction quizartinib cycles (in combination with cytarabine and anthracycline), up to 4 consolidation quizartinib cycles (in combination with high-dose cytarabine), and up to 36 maintenance quizartinib cycles; initiate quizartinib maintenance therapy after consolidation chemotherapy and following blood count recovery to ANC >500/mm3 and platelets >50,000/mm3.
Induction: Oral: 35.4 mg once daily on days 8 to 21 of the 28-day induction cycle (in combination with cytarabine and anthracycline [7+3 regimen]); if definitive evidence of (clinically significant) residual leukemia, administer a second induction cycle of 35.4 mg once daily on days 8 to 21 (in combination with cytarabine and anthracycline [7+3 regimen]) or on days 6 to 19 (in combination with cytarabine and anthracycline [5+2 regimen]) of the 28-day cycle (Ref).
Consolidation: Oral: 35.4 mg once daily on days 6 to 19 of each 28-day consolidation cycle (in combination with high-dose cytarabine) for up to 4 cycles (Ref).
Maintenance:
Cycle 1: Oral: 26.5 mg once daily on days 1 to 14 of cycle if QTcF is ≤450 msec. Increase to 53 mg once daily on days 15 to 28 of a 28-day maintenance cycle if QTcF remains ≤450 msec. Maintain a dose of 26.5 mg once daily if QTcF >500 msec was observed during induction or consolidation (Ref).
Cycle 2 and beyond: Oral: 26.5 mg or 53 mg (as determined in maintenance cycle 1) once daily on days 1 to 28 of each 28-day maintenance cycle for up to 36 cycles (Ref). For patients proceeding to hematopoietic cell transplant, discontinue quizartinib 7 days prior to initiation of conditioning regimen.
Missed doses: If dose is missed, administer as soon as possible on the same day. Return to the normal dosing schedule the following day; do not administer 2 doses on the same day. If dose is vomited, do not administer a replacement dose; administer when the next scheduled dose is due.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Note: Kidney function estimated with the Cockcroft-Gault equation.
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild impairment (Child-Pugh class A, or total bilirubin ≤ ULN and AST > ULN, or total bilirubin >1 to 1.5 times ULN and any AST) or moderate impairment (Child-Pugh class B or total bilirubin >1.5 to 3 times ULN and any AST): No dosage adjustment necessary.
Severe impairment (Child-Pugh class C or total bilirubin >3 times ULN): There are no dosage recommendations provided in the manufacturer’s labeling (has not been studied).
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Current dosage |
Reduced dosage |
|---|---|
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53 mg once daily |
35.4 mg once daily |
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35.4 mg once daily |
26.5 mg once daily |
|
26.5 mg once daily |
Interrupt therapy |
|
17.7 mg once daily |
Interrupt therapy |
|
Adverse reaction |
Severity |
Quizartinib dosage modification |
|---|---|---|
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a Granulocyte colony stimulating factor was considered in the induction phase for patients with sepsis or life-threatening infection and allowed in the consolidation phase (Erba 2023). | ||
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b See recommended ECG monitoring for quizartinib in “Monitoring Parameters”. | ||
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Hematologic toxicity | ||
|
Neutropeniaa |
Grade 4 after achieving remission |
Continue quizartinib at reduced dose. Recommend bone marrow evaluation. |
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Thrombocytopenia |
Grade 4 after achieving remission |
Continue quizartinib at reduced dose. Recommend bone marrow evaluation. |
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Nonhematologic toxicity | ||
|
Prolonged QTc interval (corrected by Fridericia formula [QTcF]) |
Grade 1 (QTcF 450 msec to 480 msec) |
Continue quizartinib at current dose. |
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Grade 2 (QTcF 481 msec to 500 msec) |
Reduce quizartinib dose without interruption. In the next cycle following dose reduction, resume quizartinib at the previous dose if QTcF has decreased to <450 msec. Monitor closely for QT prolongation for first cycle at increased dose. | |
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Grade 3 (QTcF >500 msec) |
Withhold quizartinib and monitor as clinically indicatedb; resume at reduced dose when QTcF <450 msec. QTcF >500 msec during induction or consolidation: Continue 26.5 mg once daily dose during maintenance. | |
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Grade 3 (recurrent despite dose reduction and correction/elimination of risk factors) |
Permanently discontinue quizartinib. | |
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Grade 4 (torsades de pointes, polymorphic ventricular tachycardia, signs/symptoms of life-threatening arrhythmia) |
Permanently discontinue quizartinib. | |
|
Hypokalemia |
Grade 3 or 4 (<3 mEq/L or <3 mmol/L) |
Withhold quizartinib; restart at previous dose when improved to ≤ grade 2 without symptoms. Correct hypokalemia according to institutional guidance. |
|
Hypomagnesemia |
Grade 3 or 4 (<0.9 mg/dL or <0.4 mmol/L) |
Withhold quizartinib; restart at previous dose when improved to ≤ grade 2 without symptoms. Correct hypomagnesemia according to institutional guidance. |
|
Other treatment-related adverse reaction |
Grade 3 or 4 |
Withhold quizartinib; resume treatment if adverse reaction improves to ≤ grade 2: Improvement to ≤ grade 1: Resume at previous dose. Improvement to grade 2: Resume at reduced dose. Discontinue quizartinib if grade 3 or 4 adverse reaction persists beyond 28 days. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported with combination chemotherapy in adults.
>10%:
Cardiovascular: Prolonged QT interval on ECG (14%)
Endocrine & metabolic: Decreased serum albumin (53%), decreased serum calcium (33%), decreased serum magnesium (44%), decreased serum phosphate (52%), decreased serum potassium (59%), hypermagnesemia (14%), increased serum potassium (15%), increased serum sodium (13%)
Gastrointestinal: Abdominal pain (30%), decreased appetite (17%), diarrhea (42%; grades 3/4: 8%), dyspepsia (11%), nausea (34%; grades 3/4: 2%), stomatitis (38%; grades 3/4: 5%), vomiting (25%)
Hematologic & oncologic: Anemia (11%; grades 3/4: 6%), febrile neutropenia (44%; grades 3/4: 43%), lymphocytopenia (60%; grades 3/4: 57%), neutropenia (29%; grades 3/4: 26%), thrombocytopenia (18%; grades 3/4: 13%)
Hepatic: Increased serum alkaline phosphatase (51%), increased serum transaminases (19%; including increased serum alanine aminotransaminases and increased serum aspartate aminotransferase)
Infection: Fungal infection (16%), herpes virus infection (14%), sepsis (30%)
Nervous system: Headache (28%), insomnia (14%)
Neuromuscular & skeletal: Increased creatine phosphokinase in blood specimen (26%)
Ophthalmic: Eye irritation (11%; including ulcerative keratitis)
Respiratory: Epistaxis (15%), upper respiratory tract infection (21%)
<1%: Cardiovascular: Torsades de pointes, ventricular fibrillation
Severe hypokalemia, severe hypomagnesemia, long QT syndrome, or a history of ventricular arrhythmias or torsades de pointes.
Concerns related to adverse effects:
• Cardiac effects: Torsades de pointes (TdP), ventricular fibrillation, cardiac arrest, and sudden cardiac death have occurred in less than 1% of patients treated with quizartinib, primarily in the induction phase of treatment; some cases were fatal. When used in combination with chemotherapy, a small percentage of patients experienced QTcF greater than 500 msec, and ~10% of patients had a greater than 60 msec increase in QTcF from baseline. Prolongation of the QT interval in quizartinib-treated patients occurs in a dose- and concentration-dependent manner, via inhibition of the slow delayed rectifier potassium current (IKs). As most medications prolong the QTc interval via the rapid delayed rectifier potassium current (IKr), the level of QTc prolongation that predicts cardiac arrhythmia with quizartinib is unknown. Clinical trials of quizartinib excluded patients with QTcF ≥450 msec or other high-risk factors for QT prolongation or arrhythmia. Avoid use in patients who are at significant risk of developing TdP (uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmia, tachyarrhythmia, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, and/or uncontrolled hypothyroidism).
Other warnings/precautions:
• FLT3-internal tandem duplication (ITD) mutation positivity: In the treatment of acute myeloid leukemia, quizartinib is approved for use only in patients with FLT3-ITD mutation positivity (as detected by an approved test). Information on approved tests may be found at http://www.fda.gov/CompanionDiagnostics.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as dihydrochloride:
Vanflyta: 17.7 mg, 26.5 mg
No
Tablets (Vanflyta Oral)
17.7 mg (per each): $655.20
26.5 mg (per each): $655.20
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Quizartinib is available through specialty pharmacies and various specialty institutions/accounts. Examples from the manufacturer may be found at http://www.vanflytahcp.com.
Oral: Administer with or without food at approximately the same time each day. Swallow tablets whole; do not cut, crush, or chew.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Vanflyta: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216993s000lbl.pdf#page=20
Acute myeloid leukemia, newly diagnosed, FLT3-ITD-mutated: Treatment of adult patients with newly diagnosed acute myeloid leukemia that is FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD)–positive (as detected by an approved test), in combination with standard cytarabine and anthracycline induction, cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy.
Limitations of use: Not indicated as maintenance monotherapy following allogeneic hematopoietic cell transplantation.
Vanflyta may be confused with Inlyta.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP3A4 (major), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Azithromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May decrease the serum concentration of Quizartinib. Risk X: Avoid combination
CYP3A4 Inducers (Strong): May decrease the serum concentration of Quizartinib. Risk X: Avoid combination
CYP3A4 Inhibitors (Strong): May increase the serum concentration of Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
Dabrafenib: Quizartinib may enhance the QTc-prolonging effect of Dabrafenib. Dabrafenib may decrease the serum concentration of Quizartinib. Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of Quizartinib. Encorafenib may decrease the serum concentration of Quizartinib. Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fluorouracil Products: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination
Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Midostaurin: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
OLANZapine: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
PAZOPanib: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): Quizartinib may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of other QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): Quizartinib may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk). QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the serum concentration of Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Quizartinib may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of Quizartinib. Management: If combination is necessary, reduce quizartinib dose as follows: from 53 mg daily to 26.5 mg daily; from 35.4 mg daily to 17.7 mg daily; from 26.5 mg daily to 17.7 mg daily. If taking 17.7 mg daily avoid quizartinib while on the strong CYP3A4 inhibitor. Risk D: Consider therapy modification
RisperiDONE: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Verify pregnancy status within 7 days prior to quizartinib treatment in patients who could become pregnant.
Patients who could become pregnant should use effective contraception during therapy and for 7 months after the last dose of quizartinib. Patients with partners who could become pregnant should also use effective contraception during therapy and for 4 months after the last quizartinib dose.
Based on data from animal studies, quizartinib may impair fertility.
Based on the mechanism of action, and data from animal reproduction studies, in utero exposure to quizartinib may cause fetal harm.
It is not known if quizartinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 1 month after the last dose of quizartinib.
FLT3-ITD mutation status. Serum electrolytes (potassium, magnesium) prior to therapy initiation and as clinically indicated; patients who experience vomiting or diarrhea may require more frequent electrolyte monitoring. Evaluate pregnancy status within 7 days prior to therapy initiation in patients who could become pregnant. Monitor adherence.
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Recommended ECG Monitoring During Treatment With Quizartiniba | |
|---|---|
|
Phase of therapy |
ECG monitoring frequencyb |
|
a Perform ECG at baseline and prior to initiation of each phase of therapy. b Conduct more frequent monitoring of QT interval following any dose escalation and in patients who are at significant risk of developing QT interval prolongation or torsades de pointes, experiencing diarrhea or vomiting, or on concomitant medications known to prolong the QT interval. | |
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Induction |
Once weekly |
|
Consolidation |
Once weekly |
|
Maintenance |
Once weekly for first month after dose initiation and escalation, then as clinically indicated. |
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Quizartinib is a second-generation, selective, small molecule type II inhibitor of FMS-like tyrosine kinase 3 (FLT3) (Cortes 2019; Erba 2023). Quizartinib and its active metabolite (AC886) inhibit FLT3 receptor signaling and FLT3-internal tandem duplication–dependent cell proliferation via binding to the hydrophobic region adjacent to the adenosine triphosphate (ATP) binding domain while the receptor is in the inactive state, preventing autophosphorylation of the receptor. Because of the binding conformation of quizartinib, activity is limited to FLT3-ITD mutations (Cortes 2019; Erba 2023).
Distribution: Vd: 275 L.
Protein binding: ≥99% (to plasma proteins).
Metabolism: Primarily via oxidation by CYP3A4/5; AC886 is formed and metabolized by CYP3A4/5.
Bioavailability: 71%.
Half-life elimination: Quizartinib: 81 hours; AC886: 136 hours.
Time to peak: Quizartinib: ~4 hours (range: 2 to 8 hours); AC886: 5 to 6 hours (range: 4 to 120 hours).
Excretion: Feces: 76.3% (4% as unchanged drug); urine: <2%.
Clearance: 2.23 L/hour.
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