alirocumab

Action and Spectrum

Actions and Spectrum 

alirocumab functions by preventing the PCSK9 enzyme from doing its job, which controls the quantity of LDL receptors on the surface of liver cells. In its natural state, PCSK9 attaches to LDL receptors and encourages their destruction, which causes a reduction in the clearance of LDL-C from the bloodstream.  

alirocumab increases the number of LDL receptors that are available on liver cells by decreasing PCSK9, which improves the removal of LDL-C from the blood. Patients with primary hyperlipidemia or mixed dyslipidemia should primarily be treated with alirocumab. 

Drug Interaction

Adverse Reaction

Frequency defined  

1-10% 

Injection site reactions (7.2%) 

Allergic reactions (8.6%) 

Influenza (5.7%) 

Bronchitis (4.3%) 

Cough (2.5%) 

Musculoskeletal pain (2.1%) 

Urinary tract infection (4.8%) 

Muscle spasms (3.1%) 

Contusion (2.1%) 

Liver-related disorders (2.5%) 

Diarrhea (4.7%) 

Sinusitis (3%) 

Myalgia (4.2%) 

Antidrug antibodies (4.8%) 

>10% 

Nasopharyngitis (11.3%) 

Post marketing reports 

Vasculitis 

Angioedema 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• People who have a history of allergy or hypersensitivity to alirocumab or any of its ingredients should not use alirocumab.  
• Patients who have had allergic reactions should avoid taking the medication. 

Caution: 

• Plenty of research has not been done on the usage of alirocumab during pregnancy or breast-feeding.  
• alirocumab should not be used while breastfeeding because it is unknown whether it excretes into breast milk. 
• Patients with significant liver or kidney damage have not been well examined in relation to alirocumab. 

Pregnancy / Lactation

Pregnancy warnings:     

Pregnancy category: N/A 

Lactation: Excretion 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 

Proprotein convertase subtilisin type 9 (PCSK9) on the surface of liver cells cannot attach to LDLRs because of the interaction between alirocumab and PCSK9. LDLRs are normally degraded by PCSK9, which reduces the amount of LDL cholesterol (LDL-C) removed from the bloodstream. alirocumab increases the amount of functional LDLRs present on liver cells by decreasing PCSK9, resulting in improved LDL-C clearance. 

Pharmacodynamics 

A monoclonal antibody called alirocumab binds to PCSK9, or proprotein convertase subtilisin type 9, in the blood. 

As a result of its binding to LDLRs and encouragement of their breakdown, there are fewer LDLRs available for LDL-C clearance. alirocumab boosts the expression and accessibility of LDLRs on liver cells by inhibiting PCSK9. 

Improved LDL-C clearance from the bloodstream is made possible by the increased number of functioning LDLRs on liver cells.  

alirocumab not only stops the LDLR from degrading, but it also encourages the recycling of internalized LDLRs back to the cell surface. 

Pharmacokinetics 

Absorption   

alirocumab is given subcutaneously, allowing for immediate absorption into the bloodstream. Following subcutaneous treatment, the medication is quickly absorbed, and peak plasma concentrations are obtained in 3 to 7 days. 

Distribution 

alirocumab is absorbed and then transported throughout the body by the circulation. It is anticipated that, being a monoclonal antibody, it will have a sizable volume of distribution, especially in the extracellular region. 

Metabolism 

Since alirocumab is a monoclonal antibody, its metabolism is quite low. The body does not fully metabolize it. It is anticipated that proteolysis and subsequent degradation inside the reticuloendothelial system will make up the main metabolic pathway for alirocumab. 

Elimination and excretion 

alirocumab is largely eliminated as tiny peptide fragments as a result of proteolysis and subsequent breakdown. The body then eliminates these fragments, primarily through the reticuloendothelial system. 

Adminstartion

Patient Information Leaflet

Patient information leaflet 

Generic Name: alirocumab 

Why do we use alirocumab? 

For the treatment of primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), alirocumab is recommended as an addition to diet and maximally tolerated statin medication.   

A separate indication for alirocumab is the treatment of mixed dyslipidemia, which is characterised by aberrant lipid levels and high LDL-C levels.