quizartinib (Pending FDA Approval)

Action and Spectrum

Actions and Spectrum  

quizartinib selectively binds to and inhibits the FLT3 protein kinase, which is expressed on the surface of leukemia cells. quizartinib aids in preventing the growth and survival of FLT3-ITD positive acute myeloid leukaemia (AML) cells by obstructing FLT3 signalling.  

Leukemia cells may experience cell cycle arrest and apoptosis (programmed cell death) as a result of this inhibition, which lessens the tumor load. quizartinib targets AML patients with FLT3-ITD mutations and has a rather narrow spectrum of activity.

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution:  

• quizartinib has been linked to QT interval lengthening, which raises the danger of life-threatening cardiac arrhythmias. Electrocardiograms (ECGs) should be used to check the QT interval periodically before starting quizartinib treatment and throughout. 
• The potential cardiac toxicity of quizartinib has been associated to heart failure, left ventricular dysfunction, and a reduced ejection fraction.   
• quizartinib should not be used when pregnant since it could affect developing foetuses. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion into human milk is unknown  

Pregnancy Categories:         

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.   
Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women. 
Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
Category N: There is no data available for the drug under this category.

Pharmacology

Pharmacology  

The FLT3 protein kinase is expressed on the surface of leukemia cells, and quizartinib is specifically developed to limit the activity of this enzyme, especially in patients with FLT3-ITD mutations. Leukemia cells proliferate and survive unchecked due to FLT3-ITD mutations’ constitutive activation of FLT3 signaling. 

Pharmacodynamics 

quizartinib can cause cell cycle arrest in leukemia cells by blocking FLT3 signalling. Cell growth is hampered as a result of the disruption of the G1 to S phase transition of the cell cycle. 

In acute myeloid leukemia (AML) cells that are FLT3-ITD positive, quizartinib has been demonstrated to cause apoptosis, or programmed cell death.  

Pharmacokinetics 

Absorption 

The oral route of administration for quizartinib is through capsules. It is absorbed in the gastrointestinal tract upon oral consumption. It has a bioavailability of about 33%. quizartinib can be absorbed differently depending on what you eat because eating a high-fat meal before taking it can boost its bioavailability. 

Distribution 

A significant amount of quizartinib is distributed. It has a large affinity for plasma proteins, especially albumin, with a 98% binding rate. The drug absorbs all human tissues, including bone marrow. 

Metabolism   

In the liver, quizartinib is extensively metabolized. Cytochrome P450 enzymes, especially CYP3A4, are the primary enzymes responsible for its metabolism.  

Elimination and Excretion 

With little renal excretion, quizartinib and its metabolites are mostly removed through feces. Less than 1% of the prescribed dose is excreted in urine, whereas over 86% is lost in feces. 

Adminstartion

Administration  

quizartinib capsules should be taken orally with water. Instead of chewing, crushing, or opening them, they should be consumed whole. It is advised to take the capsules with or without food. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: quizartinib (Pending FDA Approval) 

Why do we use quizartinib?  

Adult patients with acute myeloid leukemia (AML) are the target population for quizartinib therapy. quizartinib is a medication that selectively targets and inhibits the FLT3 protein kinase, which is hyperactive in FLT3-ITD positive AML, to reduce leukemia cell proliferation and survival.