daprodustat

Action and Spectrum

Actions and Spectrum:

daprodustat is a small molecule oral hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor. It is being developed as a treatment for anemia in patients with chronic kidney disease (CKD).

HIF-PH inhibitors work by increasing the levels of hypoxia-inducible factor (HIF), a transcription factor that regulates the expression of genes involved in erythropoiesis (the production of red blood cells) and oxygen homeostasis.

By increasing HIF levels, daprodustat stimulates the production of erythropoietin, a hormone that regulates red blood cell production, leading to an increase in hemoglobin levels and a reduction in the symptoms of anemia.

Drug Interaction

Adverse Reaction

Frequency Defined 

>10%  

Abdominal pain (11%)

Hypertension (24%)

1-10% 

Hypersensitivity (7%)

Dizziness (7%)

Vascular access thrombosis (5%)

Stroke (1.2%)

Myocardial infarction (3.4%)

<1% 

Pulmonary embolism (0.3%)

Deep vein thrombosis (0.7%)

Black Box Warning

Black Box Warning

The Black Box Warning for daprodustat states that there is a risk of serious renal impairment or failure, as well as an increased risk of death, in patients with moderate or severe renal impairment or who are receiving dialysis.

Contraindication / Caution

Contraindication/Caution:

Contraindications:

daprodustat is contraindicated in patients with a known hypersensitivity reaction to the drug or any of its components.

Cautions:

• daprodustat can cause elevations in serum creatinine levels, which can be indicative of impaired renal function. Therefore, it is important to monitor renal function regularly in patients taking this drug.
• It can increase the risk of thrombotic events, including myocardial infarction and stroke, particularly in patients with a history of these events.
• It can cause anemia, which may worsen symptoms of certain underlying conditions, such as heart failure or chronic kidney disease.
• It may interact with other medications, including those used to treat anemia or those that affect renal function.
• daprodustat has not been studied in pregnant or breastfeeding women, and it is not known whether it is safe to use during these times.

Pregnancy / Lactation

Pregnancy warnings:   

US FDA pregnancy category: N/A

Lactation:  

Excreted into human milk is unknown

Pregnancy Categories:        

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were lack of studies on pregnant women and no evidence of risk to the foetus in animal experiments.

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 available 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: 

daprodustat is an orally administered used to the treat anemia due to chronic kidney disease (CKD).

Pharmacodynamics: 

It works by increasing the levels of HIF, a transcription factor that regulates the production of erythropoietin, a hormone that stimulates the production of red blood cells. This results in an increase in the production of red blood cells, which helps to alleviate anemia symptoms.

Pharmacokinetics:  

Absorption 

daprodustat is an oral drug that is absorbed into the bloodstream following ingestion

Distribution 

Once absorbed, daprodustat is distributed throughout the body, including the kidneys where it can exert its effect

Metabolism 

The metabolic pathways of daprodustat are not well understood

Elimination and Excretion 

daprodustat is primarily excreted through the urine

Adminstartion

Administration: 

Oral administration

daprodustat is an oral medication that is administered once daily. It should be taken with a meal to enhance its absorption. The dose of daprodustat is adjusted based on the patient’s hemoglobin levels and their response to the medication.

Patient Information Leaflet

Patient information leaflet

Generic Name: daprodustat

Why do we use daprodustat?

daprodustat is a medication used to treat anemia, a condition where the body doesn’t produce enough red blood cells. It works by increasing the production of erythropoietin, a hormone that regulates red blood cell production. daprodustat is used in people with chronic kidney disease, as this condition can lead to anemia.