plozasiran

Action and Spectrum

Action and spectrum:    

Actions:  

 A GalNAc-conjugated small interfering RNA (siRNA) that targets and breaks down apolipoprotein C3 (apoC3) messenger RNA via an RNA interference pathway, thereby lowering both hepatic and circulating apoC3 protein levels. 

By decreasing apoC3 concentrations, it enhances the removal of triglycerides from the bloodstream. 

Drug Interaction

Adverse Reaction

Frequency Defined    

>10% 

Nausea (14%) 

Headache (16%) 

Hyperglycemia (20%) 

1-10% 

Injection site reaction (10%) 

Black Box Warning

Black Box Warning     

None 

Contraindication / Caution

Contraindication/Caution:    

Contraindications 

None 

Pregnancy / Lactation

Pregnancy Warnings:    

Pregnancy category: N/A    

Lactation: Excretion in human breastmilk is unknown    

Pregnancy categories:    

Category A: Satisfactory and well-controlled studies show no evidence of risk to the fetus in the first trimester or in the later trimester.    

Category B: No evidence of risk to fetus found in animal reproduction studies and there are not enough studies on pregnant women.    

Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women.    

Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category clearly outweigh risks over benefits. These category drugs should be prohibited for pregnant women.     

Category N: There is no data available for the drug under this category.     

Pharmacology

Pharmacology:    

A GalNAc-conjugated small interfering RNA (siRNA) that targets and breaks down apolipoprotein C3 (apoC3) messenger RNA via an RNA interference pathway, thereby lowering both hepatic and circulating apoC3 protein levels. 

By decreasing apoC3 concentrations, it enhances the removal of triglycerides from the bloodstream. 

Pharmacokinetics:     

Absorption
The drug reaches its maximum plasma level approximately six hours after dosing, with a peak concentration of around 68.5 ng/mL. 

Distribution
It shows about 78% plasma protein binding and has an estimated volume of distribution of roughly 146 L. 

Metabolism
The drug is primarily broken down by nucleases, which convert it into shorter oligonucleotides of varying lengths. 

Excretion and Elimination
Its elimination half-life is approximately 3-4 hours, and the clearance rate is about 33.8 L/ hour. 

Adminstartion

Administration:    

The drug should be injected subcutaneously into the front of the thigh or the abdomen. A healthcare professional or caregiver may also administer it in the outer part of the upper arm. Injections should be avoided in areas where the skin is irritated, bruised, red, hardened, or broken. Sites with scars or stretch marks should not be used for administration. 

Patient Information Leaflet

Patient information leaflet    

Generic Name: plozasiran 

Why do we use plozasiran?   

Plozasiran is used to lower triglyceride levels in adults with familial chylomicronemia syndrome (FCS) and is also being studied for severe hypertriglyceridemia and mixed hyperlipidemia due to its ability to significantly reduce APOC3 and triglyceride levels.