Precautions of Quizartinib

1. QT Prolongation, Torsades de Pointes, and Cardiac Arrest

Perform ECG monitoring of the QT interval more frequently in patients who are at significant risk of developing QT interval prolongation and torsades de pointes, or following dose escalation.

Monitor and correct hypokalemia and hypomagnesemia prior to and during treatment with Quizartinib. Maintain electrolytes in the normal range. Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting.

Monitor patients more frequently with ECGs if coadministration of Quizartinib with 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.

Reduce Quizartinib if QTc increases to greater than 480 ms and less than 500 ms. Interrupt and reduce Quizartinib if QTc increases to greater than 500 ms. Permanently discontinue Quizartinib in patients who develop recurrent QTc greater than 500 ms or QTc interval prolongation with signs or symptoms of  life-threatening arrhythmia.  

Quizartinib is available only through a restricted program under a REMS.

2. Quizartinib REMS

Quizartinib is available only through a restricted distribution program under a REMS called the Quizartinib REMS because of the serious risk of QT prolongation, torsades de pointes, and cardiac arrest.  

Notable requirements of the Quizartinib REMS include the following:

Prescribers must be certified in the Quizartinib REMS by enrolling and completing training.

Prescribers must counsel patients receiving Quizartinib about the risk of QT prolongation, torsades de pointes, and cardiac arrest, and provide patients with a Patient Wallet Card.

Pharmacies that dispense Quizartinib must be certified with the Quizartinib REMS and must verify prescribers are certified through the Quizartinib REMS.

3. Embryo-Fetal Toxicity

Based on findings in animals and its mechanism of action, Quizartinib can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, administration of quizartinib to pregnant rats during organogenesis at exposures 3 times the maximum recommended human dose  (MRHD) of 53 mg/day caused structural abnormalities and alterations to growth.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Quizartinib and for 7 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with Quizartinib and for 4 months after the last dose.

from FDA，2023.07