Quizartinib Dosage

Medically reviewed by Drugs.com. Last updated on Nov 28, 2023.

Usual Adult Dose for Acute Myeloid Leukemia

Recommended Treatment Course:

• Induction: Up to (2) cycles of quizartinib in combination with cytarabine and anthracycline
• Consolidation: Up to (4) cycles of quizartinib in combination with high-dose cytarabine consolidation
• Maintenance: Up to (36) cycles of quizartinib as maintenance therapy or until disease progression or unacceptable toxicity

Recommended Dosing:
INDUCTION:

• Starting Day 8 (for 7 plus 3 regimen): 35.4 mg orally once a day
• Duration: Two weeks in each 28-day cycle (Days 8 to 21)

• Starting Day 6 (for 5 plus 2 regimen as the second induction cycle): 35.4 mg orally once a day
• Duration: Two weeks in each 28-day cycle (Days 6 to 19)

CONSOLIDATION:

• Starting on Day 6: 35.4 mg orally once a day
• Duration: Two weeks in each 28-day cycle (Days 6 to 19)

MAINTENANCE:
Initiate maintenance following consolidation chemotherapy upon blood count recovery:

• Absolute neutrophil count greater than 500/mm3 and platelet count greater than 50,000/mm3

First Cycle:

• Days 1 through 14: 26.5 mg orally once a day if QTcF 450 ms or less
• Day 15: Increase dose to 53 mg orally once a day if QTcF is 450 ms or less OR continue 26.5 mg orally once a day if QTcF greater than 500 ms was observed during induction or consolidation
• Duration: Once daily with no break between cycles for up to 36 cycles

Comments:

• Initiate (or escalate) dosing only if QTcF is 450 ms or less
• Adjust dose during treatment as indicated for QTcF elevations greater than 450 ms.
• Correct electrolyte abnormalities (hypokalemia and hypomagnesemia) before and during treatment.
• Perform ECGs at baseline and then once weekly during induction and consolidation; monitor weekly for the first month during maintenance and periodically thereafter.
• Stop treatment 7 days before starting conditioning regimen in patients requiring hematopoietic stem cell transplantation.

Use: For use 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 by an FDA-approved test.

• Limitation: Not indicated as maintenance monotherapy following allogeneic hematopoietic stem cell transplantation; improvement in overall survival with this drug in this setting has not been demonstrated.

Renal Dose Adjustments

Mild to moderate renal dysfunction (CrCl 30 to 89 mL/min): No dosage adjustment recommended
Severe renal dysfunction (CrCl less than 30 mL/min): Unknown; use has not been studied

Liver Dose Adjustments

MILD OR MODERATE LIVER DYSFUNCTION: No dosage adjustment recommended
Defined As:

• Child-Pugh Class A or B
• Total bilirubin (TB) value at the upper limit of normal (ULN) or less and AST greater than the ULN
• TB value greater than 1 to 1.5 times ULN and any AST value
• TB value greater than 1.5 to 3 times ULN and any AST value

SEVERE LIVER DYSFUNCTION: Unknown; use has not been studied
Defined As:

• Child-Pugh Class C
• TB value greater than 3 times ULN and any AST value

Dose Adjustments

Treatment Modifications for Adverse Reactions:
QTcF BETWEEN 450 MS AND 480 MS (GRADE 1):

• Continue treatment dose

QTcF BETWEEN 481 MS AND 500 MS (GRADE 2):

• Reduce treatment dose without interruption
• In the next cycle, resume treatment at the previous dose if the QTcF is less than 450 ms
• Monitor for QT prolongation during the first cycle at the increased dose

QTcF GREATER THAN 500 MS (GRADE 3):

• Interrupt treatment, and then resume this drug at a reduced dose when QTcF less than 450 ms
• During maintenance, continue 26.5 mg once a day if QTcF greater than 500 ms was observed during induction or consolidation

RECURRENT QTcF GREATER THAN 500 MS (GRADE 3):

• Permanently discontinue treatment with this drug if appropriate dose reduction and correction/elimination of other risk factors (e.g., serum electrolyte abnormalities, concomitant QT prolonging medications) results in reoccurrence of QTcF greater than 500 ms

NON-HEMATOLOGIC ADVERSE REACTION (GRADE 3 OR 4):

• Interrupt treatment, and then resume at the previous dose if adverse reaction improves to Grade 1 or less
• Resume treatment at reduced dose if adverse reaction improves to Grade 2
• Discontinue treatment if Grade 3 or 4 adverse reaction persists beyond 28 days

HYPOKALEMIA OR HYPOMAGNESEMIA (GRADE 3 OR 4):
For hypokalemia (less than 3 mmol/L) or hypomagnesemia (less than 0.4 mmol/L or 0.9 mg/dL):

• Interrupt treatment and correct electrolyte abnormalities according to institutional guidelines
• May resume treatment at the previous dose when adverse reaction improves to Grade 2 or less without symptoms

TORSADES DE POINTES, POLYMORPHIC VENTRICULAR TACHYCARDIA, LIFE-THREATENING ARRYTHMIA (GRADE 4):

• Permanently discontinue this drug

NEUTROPENIA OR THROMBOCYTOPENIA AFTER REMISSION (GRADE 4):

• Reduce treatment dose and recommend bone marrow evaluation

Dose Adjustments for Adverse Reactions:

• If current dosage is 53 mg once a day, then modify dose to 35.4 mg once a day
• If current dosage is 35.4 mg once a day, then modify dose to 26.5 mg once a day
• If current dosage is 26.5 mg once a day, then interrupt treatment
• If current dosage is 17.7 mg once a day, then interrupt treatment

Dose Modifications for Strong CYP450 3A4 Inhibitors:

• If current dosage is 53 mg once a day, then modify dose to 26.5 mg once a day
• If current dosage is 35.4 mg once a day, then modify dose to 17.7 mg once a day
• If current dosage is 26.5 mg once a day, then modify dose to 17.7 mg once a day
• If current dosage is 17.7 mg once a day, then interrupt treatment for duration of strong CYP450 3A4 inhibitor use. Once inhibitor discontinued for 5 half-lives, resume treatment with this drug at previous dose.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for quizartinib. It includes a medication guide, elements to assure safe use, and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm or at www.VANFLYTAREMS.com

US BOXED WARNINGS:

• QT INTERVAL PROLONGATION AND MONITORING: This drug prolongs the QT interval in a dose- and concentration-related manner. Monitor for hypokalemia or hypomagnesemia prior to administration of this drug and then periodically; correct deficiencies as indicated. Perform ECGs to monitor QT at baseline, weekly during induction and consolidation therapy, weekly for at least the first month of maintenance, and periodically thereafter. Do not initiate treatment or escalate the dose of this drug if the QT interval corrected by Fridericia's formula (QTcF) is greater than 450 ms.
• TORSADES DE POINTES AND CARDIAC ARREST: Patients taking this drug have experienced torsades de pointes and cardiac arrest. Do not administer this drug in patients with severe hypokalemia, severe hypomagnesemia, or long QT interval.
• ADDITIONAL MONITORING: Monitor ECGs more frequently if concomitant use of drugs known to prolong the QT interval is required.
• USE WITH STRONG CYP450 3A4 INHIBITORS: Reduce the dose of this drug when used concomitantly with strong CYP450 3A4 inhibitors as they may increase quizartinib exposure.
• REMS PROGRAM: Due to the risk of QT prolongation, torsades de pointes, and cardiac arrest this drug is only available through a restricted distribution program.

CONTRAINDICATIONS:

• Severe hypokalemia
• Severe hypomagnesemia
• Long QT syndrome
• History of ventricular arrhythmias or torsade de points

Safety and efficacy have not been established in patients less than 18 years of age

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer with or without food at approximately the same time each day.
• Swallow tablets whole; do not crush, cut or chew tablets.

Missed dose recommendations:

• If a dose is vomited: Do not administer a replacement; wait until next scheduled dose.
• If a dose is missed: Take as soon as possible on the same day and take at usual schedule the next day.
• Do not take 2 doses on the same day.

Storage requirements:

• Store at room temperature between 20C to 25C (68F to 77F)
• Excursions permitted to 15C to 30C (59F to 86F)

General:

• This drug should be administered as part of combination therapy with standard cytarabine and anthracycline induction and cytarabine consolidation, and as maintenance monotherapy following consolidation chemotherapy.
• Do not administer as maintenance monotherapy after allogeneic hematopoietic stem cell transplantation.

Monitoring:

• Perform ECGs prior to induction, consolidation, and maintenance therapy.
• Evaluate ECGs once weekly during induction and consolidation, and weekly for one month after dose initiation/escalation during maintenance therapy.
• Monitor patients more frequently if taking concomitant strong CYP450 3A4 inhibitors or other QT prolonging medications.
• Assess electrolytes during treatment and maintain in normal range.

Patient advice:

• Read the FDA-approved patient labeling (Medication Guide).
• Report any symptoms of QT prolongation such as dizziness, lightheadedness, and fainting to healthcare provider.
• Read the Patient Wallet Card. Carry it at all times and show to all healthcare providers.
• Inform healthcare providers of all concomitant medications including over-the-counter medications, vitamins, and herbal products.
• Use effective contraception during treatment and understand the potential risks to the fetus if pregnancy occurs during therapy.
• Do not breastfeed during use of this drug.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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