NAV

Alirocumab

Identification

Summary

Alirocumabis a PCSK9 inhibitor used as an adjunct to manage heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease in patients who require additional lowering of LDL-cholesterol (LDL-C).

Brand Names
Praluent
Generic Name
Alirocumab
DrugBank加入数量
DB09302
Background

Alirocumab is a biopharmaceutical that obtained FDA approval in July 2015 as a second line treatment for high cholesterol in adults whose LDL-cholesterol (LDL-C) is not controlled by the combination of diet and statin treatment. It is a human monoclonal antibody part of the family of the PCSK9 inhibitors which are a novel class of anticholesterol therapeutics. From this family, it was the first agent to receive FDA approval. The FDA approval was contingent on the completion of further clinical trials to better determine efficacy and safety. PCSK9 inhibition facilitates more LDL-C clearance from the blood.

Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Protein Structure
Protein Chemical Formula
C6472H9996N1736O2032S42
蛋白质Average Weight
146000.0 Da
Sequences
Not Available
Synonyms
  • Alirocumab
External IDs
  • REGN727
  • SAR236553

Pharmacology

Indication

Alirocumab is an antibody eliciting proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor activity that is indicated for:

(i) use in reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease4, and/or

(ii) use as an adjunct to diet or use alone or in combination with other lipid-lowering therapies (statins, ezetimibe, for example) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce low-density lipoprotein cholesterol (LDL-C) levels in the body4.

Reduce drug development failure rates
Build, train, & validate machine-learning models
with evidence-based and structured datasets.
See how
Build, train, & validate predictive machine-learning models with structured datasets.
See how
Associated Conditions
Contraindications & Blackbox Warnings
Avoid life-threatening adverse drug events
Improve clinical decision support with information oncontraindications & blackbox warnings, population restrictions, harmful risks, & more.
Learn more
Avoid life-threatening adverse drug events & improve clinical decision support.
Learn more
Pharmacodynamics

Alirocumab reduces levels of PCSK9 in a concentration-dependent manner.

Mechanism of action

Alirocumab是人类IgG1单克隆antibo完全dy that binds and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), an enzyme found to have "gain of function" mutations in autosomal dominant hypercholesterolemia. PCSK9 is secreted by the liver and typically binds to the LDL receptors in serum and marks them for lysosomal degradation. In result, the LDL receptors are not able to recycle to the plasma membrane, reducing their binding to LDL-C and therefore reducing the clearance of LDL-C from plasma. Therefore by inhibiting PCSK9's actions, alirocumab allows for more LDL-C reuptake by the liver and facilitates a higher rate of clearance. Lower LDL cholesterol concentrations are associated with a reduced risk of coronary heart disease.

Target Actions Organism
AProprotein convertase subtilisin/kexin type 9
inhibitor
 Humans
Absorption

Following subcutaneous (SC) administration, alirocumab is absorbed into the bloodstream and maximum concentrations are reached at a median time of 3-7 days. The absolute availability after SC administration was 85%.

Volume of distribution

Alirocumab is mainly distributed through the circulatory system, with minimal extravascular distribution.

Protein binding

Not Available

Metabolism

Antibodies are generally metabolized by the reticuloendothelial system and degraded into small peptides and individual amino acids - therefore specific metabolism studies were not conducted. Alirocumab did not show evidence of affecting CYP 450 enzymes or transporter proteins in co-administration with statins.

Route of elimination

Not Available

Half-life

In monotherapy, the median half-life of alirocumab at steady state was 17–20 days in patients receiving alirocumab at SC doses of 75 or 150 mg every 2 weeks. As statin therapy increases the production of PCSK9, statin co-administration is thought to shorten alirocumab half-life; therefore the median apparent half-life of alirocumab was reduced to 12 days at equivalent alirocumab doses. However, this difference is not considered clinically significant and does not change dosing recommendations.

Clearance

Not Available

Adverse Effects
Improve decision support & research outcomes
With structured adverse effects data, including:blackbox warnings, adverse reactions, warning & precautions, & incidence rates.
Learn more
Improve decision support & research outcomes with our structured adverse effects data.
Learn more
Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRsBrowse all" title="" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug InteractionsLearn More" title="" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction
Integrate drug-drug
interactions in your software
Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Alirocumab.
Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Alirocumab.
Aducanumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Aducanumab.
Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Alirocumab.
Amivantamab The risk or severity of adverse effects can be increased when Alirocumab is combined with Amivantamab.
Anifrolumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Anifrolumab.
Ansuvimab The risk or severity of adverse effects can be increased when Alirocumab is combined with Ansuvimab.
Anthrax immune globulin human The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Alirocumab.
Antilymphocyte immunoglobulin (horse) The risk or severity of adverse effects can be increased when Alirocumab is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit) The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Alirocumab.
Identify potential medication risks
Easily compare up to 40 drugs with our drug interaction checker.
Get severity rating, description, and management advice.
Learn more
Food Interactions
No interactions found.

Products

Drug product information from 10+ global regions
Our datasets provide approved product information including:
dosage, form, labeller, route of administration, and marketing period.
Access now
Access drug product information from over 10 global regions.
Access now
Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image
Praluent Injection, solution 150 mg/1mL Subcutaneous Sanofi US Corporation 2019-02-15 Not applicable US flag
Praluent Injection, solution 300 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2021-03-03 Not applicable EU flag
Praluent Injection, solution 75 mg/1mL Subcutaneous sanofi-aventis U.S. LLC 2015-07-24 Not applicable US flag
Praluent Injection, solution 75 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU flag
Praluent Injection, solution 150 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2021-03-03 Not applicable EU flag
Praluent Injection, solution 75 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU flag
Praluent Solution 75 mg / mL Subcutaneous Sanofi Aventis 2016-08-13 2021-03-04 Canada flag
Praluent Injection, solution 75 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2021-03-03 Not applicable EU flag
Praluent Injection, solution 150 mg/1mL Subcutaneous Regeneron Pharmaceuticals, Inc. 2019-02-15 Not applicable US flag
Praluent Injection, solution 150 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU flag

Categories

ATC Codes
C10AX14 — Alirocumab
Drug Categories
Chemical TaxonomyProvided byClassyfire
Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available
Affected organisms
Not Available

Chemical Identifiers

UNII
PP0SHH6V16
CAS number
1245916-14-6

References

一般引用
  1. Farnier M: An evaluation of alirocumab for the treatment of hypercholesterolemia. Expert Rev Cardiovasc Ther. 2015 Dec;13(12):1307-23. doi: 10.1586/14779072.2015.1111759. Epub 2015 Nov 13. [Article]
  2. Devito F, Zito A, Ricci G, Carbonara R, Dentamaro I, Cortese F, Carbonara S, Ciccone MM: Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia. Pharmacol Res. 2015 Dec;102:168-75. doi: 10.1016/j.phrs.2015.09.021. Epub 2015 Oct 8. [Article]
  3. Authors unspecified: Alirocumab (Praluent) to Lower LDL-Cholesterol. JAMA. 2015 Sep 22-29;314(12):1284-5. doi: 10.1001/jama.2015.11372. [Article]
  4. Alirocumab FDA Label 2019 [File]
KEGG Drug
D10335
PubChem Substance
347910431
RxNav
1659152
ChEMBL
CHEMBL2109540
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Alirocumab
FDA label
Download (967 KB)

Clinical Trials

Clinical TrialsLearn More" title="" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count
4 Active Not Recruiting Treatment Peripheral Arterial Disease (PAD) 1
4 Completed Treatment Acute Coronary Syndrome (ACS)/High Cholesterol 1
4 Completed Treatment Dyslipidemia 1
4 Completed Treatment High Cholesterol 1
4 Completed Treatment High Cholesterol/Myocardial Infarction 1
4 Completed Treatment Primary Hypercholesterolemia 1
4 Completed Treatment Randomized Controlled Trials 1
4 Recruiting Treatment Acute Myocardial Infarction (AMI) 1
4 Recruiting Treatment Cardiac Allograft Vasculopathy 1
4 Recruiting Treatment Early PCSK9 Inhibitor on Ventricular Remodling 1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Form Route Strength
Injection, solution Parenteral; Subcutaneous 150 MG
Injection, solution Parenteral; Subcutaneous 300毫克
Injection, solution Parenteral; Subcutaneous 75 MG
Injection, solution Subcutaneous 150 mg/1mL
Injection, solution Subcutaneous 300 mg
Injection, solution Subcutaneous 75 mg/1mL
Solution Subcutaneous 150 mg / mL
Solution Subcutaneous 75 mg / mL
Injection, solution 150 mg/nl
Injection, solution 150 mg/ml
Injection, solution Subcutaneous
Injection, solution 75 mg/ml
Injection, solution Subcutaneous 150 mg/ml
Injection, solution Subcutaneous 75 mg/ml
Injection, solution Subcutaneous 150 mg
Injection, solution Subcutaneous 75 MG
Solution Subcutaneous 75 mg
Solution Subcutaneous 150 mg
Prices
Not Available
Patents
Not Available

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Build, predict & validate machine-learning models
Use our structured and evidence-based datasets tounlock new
insights and accelerate drug research.
Learn more
Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
Learn more
Details 1.Proprotein convertase subtilisin/kexin type 9
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Very-low-density lipoprotein particle receptor binding
Specific Function
Crucial player in the regulation of plasma cholesterol homeostasis. Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein recepto...
Gene Name
PCSK9
Uniprot ID
Q8NBP7
Uniprot Name
Proprotein convertase subtilisin/kexin type 9
分子量
74285.545 Da
References
  1. Devito F, Zito A, Ricci G, Carbonara R, Dentamaro I, Cortese F, Carbonara S, Ciccone MM: Focus on alirocumab: A PCSK9 antibody to treat hypercholesterolemia. Pharmacol Res. 2015 Dec;102:168-75. doi: 10.1016/j.phrs.2015.09.021. Epub 2015 Oct 8. [Article]

Drug created at November 11, 2015 20:54 / Updated at February 24, 2023 03:03