Detailed interpretation of Quizartinib instructions for use

1. Drug name

Generic Name: Quizartinib, Quizartinib

Product name:VANFLYTA

Other names: Quizartinib, AC220

2. Indications and scope of use

Quizatinib is mainly used for newly diagnosed patients with FLT3-ITD mutations Adult patients with acute myeloid leukemia (AML) must be treated with standard induction chemotherapy (cytarabine combined with anthracycline) and high-dose cytarabine consolidation chemotherapy. After completing the induction and consolidation courses, maintenance therapy with quizartinib can be further performed to extend the efficacy and reduce the risk of disease recurrence.

It should be noted that quizartinib is not suitable for maintenance use as a single agent after allogeneic hematopoietic stem cell transplantation. Current evidence has not shown a clear survival benefit in this setting, so it is not recommended in the guidelines as a long-term maintenance strategy after transplantation.

3. Usage, dosage and treatment cycle

Quizartinib's treatment plan is usually divided into three stages: induction phase, consolidation phase and maintenance phase. The dosage and duration of each phase are different and need to be flexibly adjusted based on the patient's bone marrow recovery.

1. How to use during the induction period

In the traditional "7+3" regimen (7 days of cytarabine + 3 days of anthracycline), quizartinib is generally administered starting on the 8th day and continues until the 21st day. If a second round of induction therapy is required, the administration time can vary according to the "7+3" or "5+2" protocol, and should be started after bone marrow reconstruction to ensure safety.

2. Dosage arrangement during the consolidation period

The consolidation phase is often combined with high-dose cytarabine, and quizartinib is generally administered on days from 6 to 19 days, lasting within 4 cycles, depending on the patient's tolerance and blood picture recovery.

3. Maintenance treatment strategy

After completing consolidation chemotherapy and achieving stable blood routine (such as recovery of neutrophil and platelet values), the maintenance phase can be entered. Maintenance therapy usually starts with a lower dose and gradually increases after observing the QT interval. Treatment can last up to 36 cycles. If significant ECG changes occur during the induction or consolidation phase, the dose during the maintenance phase may need to be kept at a lower level.

4. Common adverse reactions and monitoring points

The adverse reactions of quizartinib include blood system abnormalities, electrolyte disorders, gastrointestinal symptoms, and infections. Therefore, blood routine, electrolytes, liver function and electrocardiogram need to be closely monitored during treatment.

The more common adverse reactions include:

Neutropenia, febrile neutropenia

Electrolyte abnormalities, such as decreased potassium, magnesium, and calcium

Gastrointestinal reactions, such as diarrhea, vomiting, mucositis

Elevated liver enzymes or elevated creatinase

Increased risk of upper respiratory tract infections, fungal infections, and sepsis

QT interval prolongation (the most important clinical safety issue)

Cardiac risk is a major concern during the use of quizartinib, and electrocardiogram monitoring is required before and after treatment.

5. Storage method

Quizatinib is a film-coated tablet and should be stored at room temperature. It is generally recommended to keep it between 20°C and 25°C. Short-term deviations from 15°C to 30°C are also acceptable. Moisture and high temperature environments need to be avoided to ensure drug stability.

6. Taboo groups

Quizartinib is not recommended for use in the following situations:

Known longPatients with QT syndrome

Severe hypomagnesemia or uncorrected hypokalemia

Those who have had torsade de pointes or other serious ventricular arrhythmias in the past

These contraindications are mainly based on the risk of prolonging the QT interval of quizartinib itself. Therefore, relevant risk factors need to be eliminated before starting treatment.

7. Overview of mechanism of action

Quizatinib inhibits FLT3 kinase activity to play a role. Both itself and its main metabolite AC886 can bind to the ATP pocket region of FLT3, effectively blocking the autophosphorylation process of the FLT3 receptor, thereby cutting off downstream signal transduction and inhibiting the proliferation of leukemia cells that depend on FLT3-ITD mutations. Animal model studies suggest that quizartinib can significantly inhibit tumor burden, laying the foundation for its clinical application.

Reference materials:https://go.drugbank.com/drugs/DB12874