Quizartinib

Quizartinib is a prescription medication used in combination with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) that is FLT3 internal tandem duplication (ITD)–positive as detected using an FDA-approved test.

• Quizartinib is available under the following different brand names: Vanflyta

Common side effects of Quizartinib include:

• low white blood cell counts
• changes in levels of electrolytes in the blood
• changes in liver function tests
• low white blood cell counts with fever
• diarrhea
• mouth sores
• nausea
• stomach (abdominal) pain
• headache
• vomiting
• upper respiratory tract infections
• low platelet counts
• decreased appetite
• fungal infections
• nosebleed
• herpes virus infections
• trouble sleeping
• abnormal electrocardiogram (QT prolongation)
• upset stomach
• low red blood cell counts (anemia)
• eye irritation

Serious side effects of Quizartinib include:

• changes in the electrical activity of your heart called QT prolongation, torsades de pointes, and the heart stopping (cardiac arrest)
• serious infection throughout the body and organs (sepsis)

Rare side effects of Quizartinib include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, light-headedness, or passing out

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Tablets

• 17.7 mg
• 26.5 mg

Acute myeloid leukemia

Adult dosage

• Each cycle is 28 days
• For patients who proceed to hematopoietic stem cell transplantation, stop quizartinib 7 days before the start of a conditioning regimen
• Induction
  • May receive up to 2 cycles of induction
  • Quizartinib 35.4 mg orally once a day on days 8-21, PLUS
  • 7 + 3 regimens (cytarabine 100 or 200 mg/m2/day IV on days 1-7 plus daunorubicin 60 mg/m2/day IV or idarubicin 12 mg/m2/day IV on days 1-3)
  • Optional second induction (7+3 or 5+2 regimen [5 days cytarabine plus 2 days daunorubicin or idarubicin])
  • If the 5+2 regimen is administered as the second induction cycle, administer quizartinib on days 6-19
• Consolidation
  • Quizartinib 35.4 mg orally once a day on days 6-19, PLUS
  • Cytarabine 1.5-3 g/m2 every 12 hours on days 1, 3, and 5 for up to four cycles
• Maintenance
  • Quizartinib 26.5 mg orally once a day on days 1-14 of the first cycle if QTcF is less than 450 ms
  • Increase dose to 53 mg once daily on day 15 of the first cycle if QTcF is less than 450 ms
  • Maintain 26.5 mg orally once a day if QTcF of more than 500 ms was observed during induction or consolidation
  • Duration is once daily with no break between cycles for up to 36 cycles

Dosage Considerations – Should be Given as Follows: 

• See "Dosages"

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Quizartinib has severe interactions with no other drugs.
• Quizartinib has serious interactions with no other drugs.
• Quizartinib has serious interactions with the following drug:
  • siponimod
• Quizartinib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Contraindicated in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or in patients with a history of ventricular arrhythmias or torsades de pointes

Effects of drug abuse

• None

Short-Term Effects

• See "What Are Side Effects Associated with Using Quizartinib?"

Long-Term Effects

• See "What Are Side Effects Associated with Using Quizartinib?"

Cautions

• Based on findings in animals and its mechanism of action, fetal harm may occur when administered to pregnant women
• QT prolongation, torsades de pointes, and cardiac arrest
• QT interval prolongation in a dose- and concentration-dependent manner
• Torsades de pointes, ventricular fibrillation, cardiac arrest, and sudden death have occurred
• These severe cardiac arrhythmias occurred predominantly during the induction phase
• Avoid use in patients who are at a significant risk of developing torsades de pointes, including uncontrolled or significant cardiac disease, recent myocardial infarction, heart failure, unstable angina, bradyarrhythmia, tachyarrhythmia, uncontrolled hypertension, high-degree atrioventricular block, severe aortic stenosis, or uncontrolled hypothyroidism
• Do not initiate treatment if the QTcF interval is more than 450 ms
• Do not use in patients with severe hypokalemia, severe hypomagnesemia, long QT syndrome, or a history of ventricular arrhythmias or torsades de pointes
• Perform an ECG and correct electrolyte abnormalities before initiating
• During induction and consolidation, perform an ECG before initiation and then once weekly during treatment or more frequently as clinically indicated
• During maintenance, perform ECGs before initiation, once weekly for at least the first month following dose initiation and escalation, and as clinically indicated thereafter
• Do not escalate the dose if QTcF is more than 450 ms
• Perform ECG monitoring of the QT interval more frequently in patients who are at a significant risk of developing QT interval prolongation and torsades de pointes or following dose escalation
• Monitor and correct hypokalemia and hypomagnesemia before and during treatment
• Maintain electrolytes in the normal range
• Monitor electrolytes and ECGs more frequently in patients who experience diarrhea or vomiting
• Monitor more frequently with ECGs if coadministration of quizartinib with drugs known to prolong the QT interval
• Risk Evaluation and Mitigation Strategy (REMS) program
• Quizartinib is available only through a restricted distribution program under REMS called the VANFLYTA REMS
• Notable requirements include:
  • Prescribers must be certified by enrolling and completing training
  • Prescribers must counsel patients receiving quizartinib about the risk for 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 VANFLYTA REMS and must verify prescribers are certified through VANFLYTA REMS
  • Further information is available at www.VANFLYTAREMS.com or by telephone at 1-855-212-6670
• Drug interaction overview
  • CYP3A4 substrate
  • Strong CYP3A inhibitors
  • Reduce dose
  • Strong CYP3A inhibitor increases quizartinib systemic exposure
  • Strong or moderate CYP3A inducers
  • Avoid coadministration
  • Strong or moderate CYP3A inducers decrease quizartinib systemic exposure
• QT interval prolonging drugs
  • Monitor more frequently with ECG if coadministration with QT-prolonging drugs
  • Quizartinib with other drugs that prolong the QT interval may further increase the incidence of QT prolongation

Pregnancy and Lactation

• Based on findings from animal studies and its mechanism of action, embryofetal harm may occur when administered to pregnant women
• There are no available data on use in pregnant women to evaluate for drug-associated risk
• Pregnancy testing
  • Verify pregnancy status in women of reproductive potential within 7 days before initiating
• Contraception
  • Female of reproductive potential: Use effective contraception during treatment and for 7 months after the last dose
  • Males with female partners of reproductive potential: Use effective contraception during treatment and for 4 months after the last dose
• Infertility
  • May impair women's and men's fertility
  • These effects on fertility were reversible
• Lactation
  • There are no data on the presence of quizartinib or its metabolites in human milk or its effects on breastfed children or milk production
  • Advise women not to breastfeed during treatment and for 1 month after the last dose