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Alirocumab (Praluent)

Approved for cholesterol lowering as a PCSK9 inhibitor.

Alirocumab, used as a second-line treatment for high cholesterol for adults whose cholesterol is not controlled by diet and statin treatment. 

 

It  is used as a second-line treatment to lower LDL cholesterol for adults who have a severe form of hereditary high cholesterol and people with atherosclerosis who require additional lowering of LDL cholesterol when diet and statin treatment have not worked.

 

It significantly reduces major adverse cardiovascular events by 15% and is associated with a 15% lower risk of death from any cause.

It not known whether alirocumab prevents early death from cardiovascular disease or prevents heart attacks.

 

 

Sold under the brand name Praluent.

 

 

It is a human monoclonal antibody that is of the novel class of anti-cholesterol drugs, known as PCSK9 inhibitors.

 

Alirocumab is a human monoclonal antibody of the IgG1 isotype.

Pregnancy category AU: B1

Routes of administration: Subcutaneous

Approved for use along with diet and statin therapy for adults with heterozygotes familial hypercholesterolemia or patients with clinical atherosclerotic cardiovascular disease whose low density lipoprotein cholesterol level is elevated.

An antibody given by injection to target PCSK9, a protein that normally functions to reduce receptors on the surface of liver cells that remove LDL cholesterol from the blood.

 

It inhibits  the PCSK9 protein, which binds to the low-density lipoprotein receptor (LDLR), taking cholesterol out of circulation.

 

 

Such binding leads to the receptor being degraded, and less LDL cholesterol being removed from circulation. 

When PCSK9 is blocked, more receptors are available to eliminate LDL-cholesterol and lower blood levels of bad cholesterol.

PCSK9 binds to LDL receptors on hepatocytes, promoting receptor degradation, preventing LVL-C clearance from blood, and increases serum concentrations of LDL-C.

This drug is a human monoclonal antibody that targets PCSK9 prevents it from binding to LDL receptors, and increases the hepatic uptake of LDL-C.

Reduces LDL cholesterol levels from 36-59% compared with placebo.

Subcutaneous administration of alirocumab results in maximal suppression of free PCSK9 within 4 to 8 hours and has an apparent half-life of 17 to 20 days. 

 

 

PCSK9  inhibition is dose-dependent. 

 

 

The antibody is distributed through the circulation.

Use further reduces LDL-cholesterol with heterozygous familial hypercholesterolemia or other atherosclerotic cardiovascular disease processes by 40% when taking maximally tolerate doses of a statin..

Most common adverse events are itching, swelling, pain, and bruising at the site of injection, and nasopharyngitis.

Side effects:  nose and throat irritation, injection site reactions and bruising, flu-like symptoms, urinary tract infection, diarrhea, bronchitis and cough, and muscle pain, soreness, and spasms.

 

 

No available data on use of alirocumab in pregnant women to assess risks to the fetus, nor is there data on use in children.

Allergic reactions such as hypersensitivity vasculitis in hypersensitivity reactions have been reported.

Metabolism is probably by degradation of small peptides and amino acids.

Elimination with low concentrations saturable binding to PCSK8 and higher concentrations non saturable proteolysis.

Half-life 12 days which stat you coadministration.

Administered subcutaneously every 2 weeks.

Formulation: 75, 150 mg/ml, preservative free solutions in single use pen or prefilled syringe.

Patients with previous acute coronary syndrome (ACS), adding alirocumab to high-intensity statin therapy was associated with a reduction in the risk of recurrent ischemic cardiovascular events.

In a multicenter, randomized, double-blind, placebo-controlled trial involving 18,924 patients with ACS: participants had had an acute coronary syndrome 1 to 12 months before baseline, had low-density lipoprotein (LDL) cholesterol level of 70 mg/dL, a non-high-density lipoprotein cholesterol level of 100 mg/dL, or an apolipoprotein B level of 80 mg/dL, and were receiving high-intensity statin therapy.

In the above study they were randomly assigned to either alirocumab (75 mg) or matching placebo, given subcutaneously every 2 weeks: among patients who had a previous ACS and whose levels of atherogenic lipoproteins remained elevated despite statin therapy at a high-intensity dose or at the maximum tolerated dose, the risk of major adverse cardiovascular events was lower among those who were treated with alirocumab than among those who received placebo.

ODYSSEY OUTCOMES trial above revealed that among patients who had a previous acute coronary syndrome and who were receiving high intensity statin therapy, the risk of recurrent ischemic cardiovascular events was lower among those who received alicumab than among those who receive placebo.

It is eliminated at low concentrations by binding to its target, and at higher concentrations through a proteolytic pathway.

 

 

It is produced using Chinese hamster ovary cells transfected with recombinant DNA, that are grown in tanks.

 

 

Its FDA approval was based on lowering cholesterol alone, and not on better health outcomes, such as fewer heart attacks or longer life.

 

 

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