Skip to main content

Alirocumab

Class: Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
ATC Class: C10AX14
Chemical Name: Immunoglobulin G1, anti-(human neural apoptosis-regulated proteinase 1) (human REGN727 heavy chain), disulfide with human REGN727 κ-chain, dimer
Molecular Formula: C6472H9996N1736O2032S42
CAS Number: 1245916-14-6
Brands: Praluent

Medically reviewed by Drugs.com on Jul 26, 2021. Written by ASHP.

Introduction

Antilipemic agent; fully human IgG1 monoclonal antibody that binds to proprotein convertase subtilisin kexin type 9 (PCSK9).

Uses for Alirocumab

Prevention of Cardiovascular Events

Used for secondary prevention to reduce risk of MI, stroke, and unstable angina requiring hospitalization in patients with established cardiovascular disease.

Has been shown to substantially reduce the risk of cardiovascular events when added to hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin)-based antilipemic therapy in high-risk patients with clinical atherosclerotic cardiovascular disease (ASCVD).

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of ASCVD risk reduction. If pharmacologic therapy is needed, statins are first-line drugs of choice because of their demonstrated benefits in reducing risk of ASCVD. The addition of a nonstatin drug may be considered in certain high-risk patients who require further reduction in LDL-cholesterol concentrations.

Because of the lack of long-term safety information and cost considerations, AHA/ACC states that the benefits, safety, and costs of PCSK9 inhibitors should be discussed with the patient prior to use.

Prior to initiating a nonstatin drug, ensure that patients are treated with maximally tolerated statin therapy first and that lifestyle modifications are intensified/optimized. Because true statin intolerance is uncommon, systematically and rigorously evaluate patients for this condition to encourage adherence to evidence-based statin therapy.

Primary Hyperlipidemia

Used alone or in combination with other lipid-lowering therapies (e.g., statins, ezetimibe) as an adjunct to diet in patients with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-cholesterol concentrations.

Further reduces LDL-cholesterol concentrations by approximately 40–60% when added to maximally tolerated statin therapy or when used as monotherapy.

Alirocumab Dosage and Administration

General

  • Periodically reinforce adherence to lifestyle modifications.

  • Monitor serum LDL-cholesterol concentrations to assess response to therapy and need for dosage adjustments. For patients receiving the every-2-week regimen, measure LDL-cholesterol concentrations within 4–8 weeks of initiating therapy. For patients receiving the every-4-week (i.e., once-monthly) regimen, measure LDL-cholesterol concentrations just prior to next scheduled dose since some patients may experience considerable variation in LDL-cholesterol concentrations during dosing interval. In all patients, reassess LDL-cholesterol concentrations within 4–8 weeks of any dosage adjustment.

Administration

Sub-Q Administration

Administer sub-Q every 2 weeks or every 4 weeks (i.e., once monthly).

Injection may take up to 20 seconds to complete.

Instruct patients on proper techniques for self-administration using prefilled pen provided by manufacturer. (See Advice to Patients.)

Prior to administration, allow prefilled pens to warm to room temperature for 30–40 minutes. Do not return drug to refrigerator once removed. (See Storage under Stability.)

Inject into thigh, abdomen (except for 2-inch area around the navel), or upper arm; rotate injection sites. Do not administer into areas of active skin disease or injury (e.g., sunburns, rashes, inflammation, infections), or any area that is tender, irritated, erythematous, or that has visible veins, scars, or stretch marks.

Do not administer with other drugs at the same injection site.

If a dose is missed, administer as soon as remembered within 7 days. If the missed dose is not administered within 7 days in a patient receiving the every-2-week regimen, withhold dose and administer next dose at regularly scheduled time. If the missed dose is not administered within 7 days in a patient receiving the every-4-week regimen, administer the dose and initiate a new dosing schedule starting on that date.

Contains no preservatives; intended for single use only.

Dosage

Adults

Prevention of Cardiovascular Events
Secondary Prevention in Adults with Established Cardiovascular Disease
Sub-Q

Initially, 75 mg every 2 weeks. In clinical studies, most patients were able to achieve sufficient LDL-cholesterol reduction with this dosage. Monitor LDL-cholesterol concentrations within 4–8 weeks after initiation of therapy; may increase dosage to maximum of 150 mg every 2 weeks if response is inadequate.

Alternatively, for patients who prefer less frequent dosing, may administer initial dosage of 300 mg (2 consecutive 150-mg injections at 2 different injection sites) every 4 weeks (i.e., once monthly). Monitor LDL-cholesterol concentrations just prior to next scheduled dose; may adjust dosage to 150 mg every 2 weeks if response is inadequate (administer first dose of new regimen on the date of next scheduled dose of previous regimen).

Reassess LDL-cholesterol concentrations within 4–8 weeks of dosage adjustments.

Dyslipidemias
Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)
Sub-Q

Initially, 75 mg every 2 weeks. In clinical studies, most patients were able to achieve sufficient LDL-cholesterol reduction with this dosage. Monitor LDL-cholesterol concentrations within 4–8 weeks after initiation of therapy; may increase dosage to maximum of 150 mg every 2 weeks if response is inadequate.

Alternatively, for patients who prefer less frequent dosing, may administer initial dosage of 300 mg (2 consecutive 150-mg injections at 2 different injection sites) every 4 weeks (i.e., once monthly). Monitor LDL-cholesterol concentrations just prior to next scheduled dose; may adjust dosage to 150 mg every 2 weeks if response is inadequate (administer first dose of new regimen on the date of next scheduled dose of previous regimen).

Reassess LDL-cholesterol concentrations within 4–8 weeks of dosage adjustments.

In adults with heterozygous familial hypercholesterolemia undergoing LDL apheresis, recommended dosage is 150 mg every 2 weeks. May administer without regard to timing of the procedure.

Prescribing Limits

Adults

Prevention of Cardiovascular Events
Secondary Prevention in Adults with Established Cardiovascular Disease
Sub-Q

150 mg every 2 weeks.

Dyslipidemias
Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)
Sub-Q

150 mg every 2 weeks.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No dosage adjustment necessary.

Severe hepatic impairment: Data are lacking.

Renal Impairment

Mild or moderate renal impairment: No dosage adjustment necessary.

Severe hepatic impairment: Data are lacking.

Geriatric Patients

No specific dosage recommendations.

Other Special Populations

Dosage adjustments based on age, body weight, gender, or race not required.

Cautions for Alirocumab

Contraindications

  • History of serious hypersensitivity reaction to alirocumab. (See Sensitivity Reactions under Cautions.)

Warnings/Precautions

Sensitivity Reactions

Serious hypersensitivity reactions, including angioedema, vasculitis, and nummular eczema, reported; in some cases, hospitalization was required.

If a serious hypersensitivity reaction occurs, discontinue drug and initiate standard of care treatment; monitor patient until signs and symptoms resolve. (See Contraindications under Cautions.)

Immunogenicity

Development of anti-alirocumab antibodies reported, some of which were neutralizing. Efficacy in terms of LDL-cholesterol reduction generally similar among patients who developed antibodies and those who did not; however, some patients with persistent or neutralizing antibodies experienced an attenuated response. Antibody-positive patients appeared to have a higher incidence of injection site reactions than those who did not have antibodies.

Long-term effects of continued alirocumab therapy in the presence of such antibodies not known.

Specific Populations

Pregnancy

No adequate and well-controlled studies in pregnant women. Weigh potential benefits versus possible risk to fetus.

Adverse developmental effects not observed in animal studies; however, suppression of humoral immune response observed in infant monkeys exposed to the drug in utero.

Pregnancy registry at 877-311-8792 or .

Lactation

Not known whether distributed into human milk. Human IgG is distributed into human milk; however, published data suggest that IgG antibodies in human milk are not substantially distributed into the circulation of neonates and infants.

Weigh known benefits of breastfeeding against potential adverse effects of the drug on the infant, taking into account the importance of the drug to the woman.

Pediatric Use

Safety and efficacy not established.

Geriatric Use

No overall differences in efficacy or safety relative to younger adults; however, possibility of increased sensitivity cannot be ruled out.

Hepatic Impairment

Pharmacokinetics of alirocumab not substantially altered by mild or moderate hepatic impairment.

Safety and efficacy not established in patients with severe hepatic impairment.

Renal Impairment

Renal function not expected to affect pharmacokinetics of alirocumab.

Safety and efficacy not established in patients with severe renal impairment.

Common Adverse Effects

Primary hyperlipidemia studies: Nasopharyngitis, injection site reactions (e.g., erythema/redness, itching, swelling, pain/tenderness), influenza, urinary tract infection, diarrhea, bronchitis, myalgia, muscle spasms, sinusitis, cough, contusion, musculoskeletal pain.

Cardiovascular outcomes study: Noncardiac chest pain, nasopharyngitis, myalgia.

Low levels (<25 mg/dL) and very low levels (<15 mg/dL) of LDL cholesterol occurred in some patients in clinical studies; however, long-term, prolonged effects not known.

Interactions for Alirocumab

Not expected to affect CYP isoenzymes (e.g., CYP3A4, CYP2C9) or transport proteins such as P-glycoprotein (P-gp) and organic anion transport protein (OATP).

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP substrates: Pharmacokinetic interactions unlikely.

Drugs Affected by Transport Systems

Substrates of P-gp or OATP: Pharmacokinetic interactions unlikely.

Specific Drugs

Drug

Interaction

Comments

HMG-CoA reductase inhibitors (statins)

Decreased half-life of alirocumab to 12 days; however, not clinically important

Atorvastatin: No clinically important changes in the statin concentration observed

Rosuvastatin: No clinically important changes in the statin concentration observed

No dosage adjustments necessary

Alirocumab Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 85% after sub-Q injection.

Monthly dose-normalized exposure is similar between patients receiving dosage of 300 mg every 4 weeks and those receiving dosage of 150 mg every 2 weeks.

Onset

Following sub-Q administration, maximal suppression of free PCSK9 occurs within 4–8 hours. In healthy individuals, maximal reduction in LDL-cholesterol concentrations observed 15 days after injection.

Plasma Concentrations

Peak plasma concentrations achieved in 3–7 days.

Slightly greater than dose-proportional increases in plasma concentration observed with increased doses.

Steady-state concentrations achieved after 2–3 doses; accumulation ratio up to maximum of approximately twofold.

Distribution

Extent

Distributed principally into circulatory system.

Crosses the placenta.

Not known whether distributed into milk.

Elimination

Metabolism

Expected to be degraded into small peptides and individual amino acids.

Elimination Route

At low concentrations, elimination occurs principally through saturable binding to the PCSK9 target.

At high concentrations, elimination occurs principally through a nonsaturable proteolytic pathway.

Half-life

Approximately 17–20 days.

Stability

Storage

Parenteral

Solution for Injection

2–8°C. Store in original carton to protect from light. Do not shake, freeze, or expose to extreme heat or direct sunlight.

If necessary, may store at room temperature (up to 25°C) for up to 30 days. Must use within 30 days after removal from refrigeration.

Actions

  • Fully human IgG1 monoclonal antibody that binds to PCSK9. Produced by recombinant DNA technology.

  • PCSK9 is a serine protease produced principally in the liver. Major function of PCSK9 is to promote degradation of LDL receptors, the primary receptors responsible for clearing circulating LDL cholesterol.

  • Alirocumab binds specifically and with high affinity to PCSK9; inhibition of PCSK9 increases number of receptors available to clear LDL cholesterol, and consequently reduces plasma concentrations of LDL cholesterol.

  • Reductions in lipoprotein (a), apolipoprotein B, and other lipid fractions also demonstrated.

Advice to Patients

  • Importance of patients reading the manufacturer’s patient information and instructions for use prior to starting therapy and each time the prescription is refilled.

  • Importance of discontinuing alirocumab and promptly seeking medical attention if any signs or symptoms of serious hypersensitivity (e.g., severe pruritus, rash, or redness; swollen face; difficulty breathing) occur. (See Sensitivity Reactions under Cautions.)

  • Importance of instructing patients and/or caregivers regarding proper preparation and sub-Q administration of alirocumab, including use of aseptic technique and safe disposal of the prefilled pens in a puncture-resistant container. Importance of informing patients that injection of alirocumab may take up to 20 seconds.

  • Importance of instructing patients on proper storage of the drug.

  • Importance of instructing patients not to reuse the prefilled pens.

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Importance of encouraging women who become pregnant while receiving alirocumab to participate in the pregnancy registry. (See Pregnancy under Cautions.)

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Alirocumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for subcutaneous use

75 mg/mL

Praluent (available as single-dose prefilled injection pens)

Sanofi-Aventis and Regeneron

150 mg/mL

Praluent (available as single-dose prefilled injection pens)

Sanofi-Aventis and Regeneron

AHFS DI Essentials™. © Copyright 2022, Selected Revisions July 26, 2021. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

Show article references

Frequently asked questions