Quizartinib
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From MedlinePlus, U.S. National Library of Medicine
Boxed warning
WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST VANFLYTA prolongs the QT interval in a dose- and concentration-related manner [see Clinical Pharmacology (12.2) ] . Prior to VANFLYTA 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 [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ]. Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA.
Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome [see Contraindications (4) and Warnings and Precautions (5.1) ] . Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia's formula (QTcF) is greater than 450 ms [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] . Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required [see Dosage and Administration (2.3) and Warnings and Precautions (5.1) ] .
Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure [see Dosage and Administration (2.4) and Warnings and Precautions (5.1) ] . Because of the risk of QT prolongation, VANFLYTA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the VANFLYTA REMS [see Warnings and Precautions (5.2) ] . WARNING: QT PROLONGATION, TORSADES DE POINTES, and CARDIAC ARREST See full prescribing information for complete boxed warning. VANFLYTA prolongs the QT interval.
( 12.2 ) Prior to VANFLYTA administration and periodically, perform electrocardiograms (ECGs), monitor for hypokalemia or hypomagnesemia, and correct deficiencies. ( 2.3 , 5.1 ) Torsades de pointes and cardiac arrest have occurred in patients receiving VANFLYTA. Do not administer VANFLYTA to patients with severe hypokalemia, severe hypomagnesemia, or long QT syndrome. ( 4 , 5.1 ) Do not initiate treatment with VANFLYTA or escalate the VANFLYTA dose if the QT interval corrected by Fridericia's formula (QTcF) is greater than 450 ms. ( 2.3 , 5.1 ) Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required.
( 2.3 , 5.1 ) Reduce the VANFLYTA dose when used concomitantly with strong CYP3A inhibitors, as they may increase quizartinib exposure. ( 2.4 , 5.1 )…
Dosing in kidney impairment
Renal Impairment No dosage adjustment is recommended in patients with mild to moderate renal impairment (i.e., estimated creatinine clearance [CLcr] by Cockcroft-Gault equation: CLcr 30 to 89 mL/min). VANFLYTA has not been studied in patients with severe renal impairment (CLcr <30 mL/min) [see Clinical Pharmacology ] .
Dosing in liver impairment
Hepatic Impairment No dosage adjustment is recommended in patients with mild hepatic impairment (Child-Pugh Class A or total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] >ULN, or total bilirubin >1 to 1.5 times ULN and any value for AST) or moderate hepatic impairment (Child-Pugh Class B or total bilirubin >1.5 to 3 times ULN and any value for AST).
VANFLYTA has not been studied in patients with severe (Child-Pugh Class C or total bilirubin >3 times ULN and any value for AST) hepatic impairment [see Clinical Pharmacology ] .
Drug interactions
Check quizartinib against a medication listLabel text (4 paragraphs)
Table 7: Effect of Other Drugs on VANFLYTA Strong CYP3A Inhibitors Clinical Impact VANFLYTA is a CYP3A substrate. Concomitant use of VANFLYTA with a strong CYP3A inhibitor increases quizartinib systemic exposure [see Clinical Pharmacology (12.3) ] , which may increase the risk of VANFLYTA adverse reactions. Prevention or Management Reduce the dosage of VANFLYTA [see Dosage and Administration (2.4) ]. Strong or Moderate CYP3A Inducers Clinical Impact Concomitant use of VANFLYTA with strong or moderate CYP3A inducers decreases quizartinib systemic exposure [see Clinical Pharmacology (12.3) ] , which may reduce VANFLYTA efficacy.
Prevention or Management Avoid concomitant use of VANFLYTA with strong or moderate CYP3A inducers [see Clinical Pharmacology (12.3) ] . QT Interval Prolonging Drugs Clinical Impact VANFLYTA prolongs the QT/QTc interval. Coadministration of VANFLYTA with other drugs that prolong the QT interval may further increase the incidence of QT prolongation [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2) ] . Prevention or Management Monitor patients more frequently with ECG if co-administration of VANFLYTA with drugs known to prolong the QT interval is required.
Examples of QT prolonging drugs include but are not limited to antifungal azoles, ondansetron, granisetron, azithromycin, pentamidine, doxycycline, moxifloxacin, atovaquone, prochlorperazine, and tacrolimus. Breast Cancer Resistant Protein (BCRP) Substrates Clinical Impact Concomitant use of VANFLYTA with BCRP substrates may increase the risk of BCRP substrate-associated adverse reactions [see Clinical Pharmacology (12.3) ] . Prevention or Management Avoid concomitant use of VANFLYTA with drugs that are BCRP substrates where possible.
If concomitant use is unavoidable, monitor patients more frequently for BCRP substrate-associated adverse reactions and decrease the BCRP substrates dosage(s) in accordance with the respective Prescribing Information. Strong CYP3A Inhibitors: Reduce the VANFLYTA dose. ( 2.4 , 7 ) Strong or Moderate CYP3A Inducers: Avoid concomitant use. ( 7 , 12.3 ) Breast Cancer Resistant Protein (BCRP) substrates: Avoid concomitant use. ( 7 , 12.3 )
Contraindications
4 CONTRAINDICATIONS VANFLYTA is contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes [see Warnings and Precautions (5.1) ]. Contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes. ( 4 , 5.1 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, VANFLYTA can cause embryo-fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on VANFLYTA use in pregnant women to evaluate for a drug-associated risk. In animal reproduction studies, oral administration of quizartinib to pregnant rats during organogenesis resulted in adverse developmental outcomes including structural abnormalities and alterations to growth at maternal exposures approximately 3 times those in patients at the maximum recommended human dose (MRHD) of 53 mg/day ( see Data ).
Advise pregnant women of the potential risk to a fetus. The background risk in the U.S. general population of major birth defects is 2-4%, and of miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data In an embryo-fetal development study in rats, pregnant animals received oral doses of quizartinib of 0, 0.6, 2, or 6 mg/kg/day during the period of organogenesis. Administration of quizartinib at the dose of 6 mg/kg/day was associated with adverse developmental outcomes including structural abnormalities (anasarca and edema) and alterations to growth (lower fetal weights and effects on skeletal ossification).
At this dose, the maternal systemic exposures (AUC) were approximately 3 times the human exposure at the MRHD of 53 mg/day.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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