ripretinib

Action and Spectrum

Actions and Spectrum 

ripretinib works by preventing specific enzymes known as kinases from functioning, namely KIT and PDGFRA kinases. These kinases are essential for the development and survival of the cells that make up gastrointestinal stromal tumors (GISTs).  

ripretinib helps in slowing the growth of GIST tumors and may cause tumor shrinking by obstructing the activation of these kinases. Adult patients with advanced GISTs are treated with ripretinib.

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

All grades 

Decreased neutrophil count (10%) 

Grade 3-4 

Increased lipase (7%)  

Decreased appetite (1.2%) 

Myalgia (1.2%) 

Decreased sodium (2.4%) 

Increased INR (3.8%)  

Peripheral edema (1.2%) 

Asthenia (1.2%) 

Increased ALT (1.2%) 

Constipation (1.2%) 

Diarrhea (1.2%) 

Increased triglycerides (2.4%) 

Fatigue (3.5%) 

Decreased phosphate (4.9%)  

Increased serum amylase (1.2%) 

Nausea (3.5%) 

Increased CPK (1.2%) 

Vomiting (3.5%) 

Abdominal pain (7%) 

Hypertension (7%) 

>10% 

All grades 

Stomatitis (11%) 

Myalgia (32%) 

Decreased phosphate (26%)  

Peripheral edema (17%) 

Increased creatinine (16%)  

Increased ALT (12%) 

Pruritus (11%) 

Hypertension (14%) 

Increased lipase (32%) 

Alopecia (52%)  

Increased triglycerides (26%) 

Muscle spasms (15%) 

Decreased weight (19%) 

Headache (19%) 

Decreased sodium (17%) 

Arthralgia (18%) 

Decreased calcium (23%) 

Increased blood bilirubin (22%) 

Decreased appetite (27%)  

Dyspnea (13%) 

Increased serum amylase (13%) 

Asthenia (13%) 

Abdominal pain (36%)  

Constipation (34%) 

PPES (21%) 

Dry skin (13%) 

Increased CPK (21%) 

Vomiting (21%) 

Diarrhea (28%) 

Increased aPTT (35%) 

Fatigue (42%) 

Nausea (39%) 

Increased INR (21%) 

Post marketing Reports 

Photosensitivity 

Black Box Warning

Black Box Warning 

None  

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• People with a history of allergy or hypersensitivity to ripretinib or any of its ingredients should not take it. 

Caution: 

• Patients who show moderate to severe hepatic impairment should be treated cautiously when taking the medication. 
• ripretinib may have harmful consequences on the heart, such as left ventricular dysfunction and cardiac failure.  
• ripretinib may result in gastrointestinal side effects such diarrhoea, nausea, vomiting, and discomfort in the abdomen. 

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  

KIT and platelet-derived growth factor receptor alpha (PDGFRA) kinases are among the kinases that ripretinib blocks from acting. It accomplishes this by attaching to the ATP-binding site of these kinases and blocking the transfer of phosphate groups required for kinase activation. 

Pharmacodynamics 

ripretinib prevents these kinases from activating by attaching to their ATP binding site and obstructing downstream signaling pathways essential in tumor growth, proliferation, and survival. This KIT and PDGFRA inhibition are especially important when it comes to gastrointestinal stromal tumors (GISTs), which frequently have unique mutations in these kinases.  

Angiogenesis, the mechanism by which new blood vessels emerge to assist tumor growth, has also been demonstrated to be inhibited by ripretinib. 

Pharmacokinetics 

Absorption   

ripretinib tablets are used for oral administration. After consumption, it is readily absorbed, and peak plasma concentrations are usually attained in 4 to 6 hours. Food consumption has little impact on how well ripretinib is absorbed. 

Distribution 

For plasma proteins, especially albumin, ripretinib has a high affinity for binding. In addition to being widely disseminated throughout the body, it also has a large volume of dispersion. 

Metabolism 

ripretinib is extensively metabolized in the liver, mostly by the cytochrome P450 enzyme CYP3A4. Its N-oxide metabolite, which also has inhibitory effect against KIT and PDGFRA kinases, is the main active metabolite of ripretinib.  

Elimination and excretion 

The majority of ripretinib and its metabolites are excreted in the feces (69%), while a lesser amount is eliminated in the urine (19%). ripretinib has an elimination half-life of roughly 15 hours. 

Adminstartion

Administration 

ripretinib is available in the form of oral tablets and is typically administered once daily.  

ripretinib tablets should be inhaled whole along with water. Before eating, they should not be chewed, fractured or crushed. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ripretinib 

Why do we use ripretinib? 

For the treatment purpose in adult patients with advanced gastrointestinal stromal tumors (GISTs), ripretinib is recommended.   

It is used specifically when a tumor cannot be surgically removed or has spread to other sections of the body.