Identification
- Summary
Alirocumab is 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 Accession Number
- 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
- Protein 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 disease 4, 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 body 4.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Adjunct therapy in management of Heterozygous familial hypercholesterolemia (hefh) •••••••••••• ••••• ••••••••• Adjunct therapy in management of Heterozygous familial hypercholesterolemia (hefh) •••••••••••• ••••• ••••••••• Adjunct therapy in management of Homozygous familial hypercholesterolaemia (hofh) •••••••••••• ••••• ••••••••• Prevention of Myocardial infarction •••••••••••• ••••• ••••••••••• •••••••••••••• ••••••• ••••••••• Prevention of Stroke •••••••••••• ••••• ••••••••••• •••••••••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Alirocumab reduces levels of PCSK9 in a concentration-dependent manner.
- Mechanism of action
Alirocumab is a fully human IgG1 monoclonal antibody 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 inhibitorHumans - 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
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" 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 softwareAbciximab 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. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Praluent Injection, solution 150 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU 
Praluent Injection, solution 75 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU Praluent Injection, solution 75 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2016-09-08 Not applicable EU Praluent Injection, solution 300 mg Subcutaneous SANOFI WINTHROP INDUSTRIE 2021-03-03 Not applicable EU Praluent Solution 75 mg / mL Subcutaneous Sanofi Aventis 2016-08-13 2021-03-04 Canada 
Categories
- ATC Codes
- C10AX14 — Alirocumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Anticholesteremic Agents
- Antimetabolites
- Blood Proteins
- Enzyme Inhibitors
- Globulins
- Hypercholesterolemia, drug therapy
- Hypolipidemic Agents
- Hypolipidemic Agents Indicated for Hyperlipidemia
- Immunoglobulins
- Immunoproteins
- Lipid Modifying Agents
- Lipid Modifying Agents, Plain
- Lipid Regulating Agents
- Non-statin Hypolipidemic Agents Indicated for Hyperlipidemia
- PCSK9 Inhibitor
- Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
- Protease Inhibitors
- Proteins
- Serine Protease Inhibitors
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- 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
- General References
- 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]
- 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]
- Authors unspecified: Alirocumab (Praluent) to Lower LDL-Cholesterol. JAMA. 2015 Sep 22-29;314(12):1284-5. doi: 10.1001/jama.2015.11372. [Article]
- Alirocumab FDA Label 2019 [File]
- External Links
- KEGG Drug
- D10335
- PubChem Substance
- 347910431
- 1659152
- ChEMBL
- CHEMBL2109540
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Alirocumab
- FDA label
- Download (967 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 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 Peripheral Arterial Disease (PAD) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Parenteral; Subcutaneous 150 MG Injection, solution Parenteral; Subcutaneous 300 MG 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/ml Injection, solution 150 mg/nl 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
- 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
- Molecular Weight
- 74285.545 Da
References
- 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 November 01, 2023 04:04