dovitinib (Pending FDA Approval)

Action and Spectrum

Actions and Spectrum  

Multiple receptor tyrosine kinases, such as the fibroblast growth factor receptors, vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors, are specifically inhibited by dovitinib.  

dovitinib prevents angiogenesis, or the growth of new blood vessels, in a significant way by inhibiting VEGFRs. Fibroblast growth factor receptors are involved in angiogenesis and the formation of tumors. Receptors for platelet-derived growth factors, which are involved in angiogenesis and tumor formation. 

Drug Interaction

Adverse Reaction

None

Black Box Warning

Black Box Warning: 

None 

Contraindication / Caution

Contraindication/Caution:  

Contraindication: 

• Any known allergic or hypersensitive reactions to dovitinib or any of its ingredients.  

Caution: 

• Patients with pre-existing liver impairment should use caution when using dovitinib because it may result in hepatotoxicity (liver damage). 
• Patients with history of heart issues or who have pre-existing cardiac diseases should be properly watched during treatment. 
• Patients with compromised renal function may need to alter their dosage because dovitinib is predominantly excreted through the kidneys.  
• Patients undergoing anticoagulant treatment or those with a history of bleeding issues should use caution. 

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  

dovitinib blocks the signaling pathways of numerous RTKs by competitively inhibiting their ATP (adenosine triphosphate) binding sites. Fibroblast growth factor receptors, vascular endothelial growth factor receptors, and platelet-derived growth factor receptors are among the important RTKs whose activity is inhibited in tumor growth, angiogenesis, and metastasis.  

dovitinib interferes with these mechanisms, hence preventing the growth, survival, and angiogenesis of cancer cells. 

Pharmacodynamics 

dovitinib inhibits several RTKs, which prevents the signals that promote cell division and growth and has anti-proliferative properties. In order to further increase its anticancer efficacy, it can encourage the apoptosis (programmed cell death) of cancer cells. 

The tumour microenvironment can be altered by dovitinib’s effects on RTKs involved in angiogenesis and tumor-stromal interactions. It can hinder the growth of new blood vessels and lessen the delivery of nutrients to the tumour by interfering with pro-angiogenic signalling. 

Pharmacokinetics 

Absorption  

Oral administration of dovitinib results in absorption of the medication into the bloodstream from the gastrointestinal system. It is normally advised to take dovitinib on an empty stomach because food has a moderate impact on how well the drug is absorbed. 

Distribution    

dovitinib is dispersed all over the body. It has a strong affinity for albumin and other plasma proteins. There is little information on how the medication enters tissues and organs. 

Metabolism   

The liver is where dovitinib is largely metabolized. Enzymes mediate the major metabolic pathway, with CYP3A4 serving as the key enzyme. Several metabolites are produced as a result of dovitinib’s metabolism.  

Elimination and Excretion   

dovitinib and its metabolites are predominantly excreted in the feces, with a lesser amount also passing through the urine. Both the medication and its metabolites are either excreted conjugated or unmodified. 

Adminstartion

Administration  

dovitinib is administered orally in the form of capsules.

Patient Information Leaflet

Patient information leaflet 

Generic Name: dovitinib (Pending FDA Approval) 

Why do we use dovitinib? 

A kind of kidney cancer called advanced or metastatic renal cell carcinoma has been studied with dovitinib. Clinical investigations have demonstrated that it is effective at reducing tumor angiogenesis and proliferation. 

Patients with GIST who had previously responded poorly to other targeted treatments like imatinib have been investigated with dovitinib. It has demonstrated potential for slowing the spread of disease and preventing tumor growth.