zibotentan and dapagliflozin

Action and Spectrum

Actions and spectrum: 

zibotentan: zibotentan is an endothelin receptor antagonist, which means it blocks the action of endothelin, a substance that can narrow blood vessels. This class of medications has been studied for potential use in conditions like prostate cancer. 

dapagliflozin: It is the sodium glucose co-transporter 2 (SGLT2) inhibitor used primarily to treat type 2 diabetes. It works by reducing the reabsorption of glucose by kidneys, leading to increased glucose excretion in the urine. 

Drug Interaction

Adverse Reaction

N/A 

Black Box Warning

Black Box Warning: 

There is no specific black box warning associated with zibotentan and dapagliflozin. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication 

• Hypersensitivity: zibotentan/ dapagliflozin is contraindicated in individuals with known hypersensitivity or allergic reaction to drug or its components.  
• Pregnancy and Lactation: zibotentan is contraindicated during pregnancy and lactation unless the potential benefits outweigh the risks.  
• Type 1 Diabetes Mellitus: dapagliflozin is not indicated for the treatment of type 1 diabetes.  
• Ketoacidosis: dapagliflozin is contraindicated in patients with a history of ketoacidosis. 

Caution 

• Hepatic Impairment: Caution is advised in hepatic impairment. Close monitoring of liver function may be necessary.  
• Hypertension: The Blood pressure should be monitored during treatment, and adjustments to antihypertensive therapy may be necessary.  
• Genital Mycotic Infections: dapagliflozin increases the risk of genital mycotic infections. Patients should be educated on hygiene practices, and treatment may be necessary if infections occur.

Comorbidities 

• Cardiovascular Effects: zibotentan may have cardiovascular effects, and caution is recommended in patients with a history of cardiovascular disease.  
• Severe Renal Impairment: dapagliflozin is contraindicated in individuals with severe renal impairment or in end stage renal disease. 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category: not assigned 

Lactation: excreted into human milk: unknown  

Pregnancy category: 

• 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: 

• zibotentan: zibotentan is an endothelin receptor antagonist, acting specifically on endothelin receptors. Endothelin is a peptide that plays a role in regulating blood vessel constriction. By blocking endothelin receptors, zibotentan aims to dilate blood vessels, potentially impacting conditions such as hypertension or certain cancers. 
• dapagliflozin: It is the sodium glucose co-transporter 2 (SGLT2) inhibitor used in type 2 diabetes. It works by inhibiting SGLT2 in the kidneys, reducing glucose reabsorption, and promoting the excretion of glucose in the urine, thereby lowering blood glucose levels. 

Pharmacodynamics: 

• zibotentan: By blocking endothelin A receptors, zibotentan aims to reduce the effects of endothelin, a peptide that can contribute to blood vessel constriction and cell proliferation. It is primarily investigated for its potential use in the treatment of prostate cancer. 
• dapagliflozin: It helps lower blood glucose levels by promoting the elimination of excess glucose through the urine. It is primarily used in the management of type 2 diabetes mellitus. 

Pharmacokinetics: 

zibotentan: 

• Absorption: zibotentan is orally administered and is expected to be absorbed from the gastrointestinal tract. 
• Distribution: It distributes throughout the body, and binding to plasma proteins may occur. 
• Metabolism: zibotentan undergoes hepatic metabolism, primarily through cytochrome P450 enzymes. 
• Excretion: The metabolites are excreted through feces, with a smaller portion eliminated in urine. 

dapagliflozin: 

• Absorption: dapagliflozin is rapidly absorbed following oral administration. 
• Distribution: It has a moderate volume of distribution, and it binds minimally to plasma proteins. 
• Metabolism: dapagliflozin undergoes minimal metabolism. 
• Excretion: The majority of dapagliflozin is excreted unchanged in the urine. 

Adminstartion

Administration: 

N/A 

Patient Information Leaflet

Patient information leaflet 

Generic Name: zibotentan and dapagliflozin 

Pronounced: (zi-BOT-en-tan-and- da-pa-GLIF-lo-zin)  

Why do we use zibotentan and dapagliflozin? 

The use of the combination of zibotentan and dapagliflozin to treat CKD is still in the early stages of development. However, the results of the ZENITH-CKD trial are promising and suggest that the combination could be a new and effective treatment for CKD.