Alirocumab (Monograph)

Brand name: Praluent
Drug 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

Medically reviewed by Drugs.com on Dec 13, 2024. 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 adults with established cardiovascular disease.

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of atherosclerotic cardiovascular disease (ASCVD) risk reduction. If pharmacologic therapy is needed, hydroxymethyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) are the first-line drugs of choice. Certain patient groups may benefit from the addition of a nonstatin drug such as a PCSK9 inhibitor if maximally tolerated statin therapy is insufficient to achieve goal reductions in LDL cholesterol concentrations. Patients who are intolerant of at least 2 statin therapies with one attempt using the lowest approved daily dosage may also be considered for treatment with nonstatin drugs.

Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)

Used alone or in combination with other LDL-cholesterol-lowering therapies as an adjunct to diet in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce LDL-cholesterol concentrations.

Current treatments for patients with HeFH include lifestyle modifications (e.g., low-fat diet, maintenance of a healthy body weight, smoking cessation), first-line treatment with statins, and, if necessary, combination therapy with other lipid-lowering medications (e.g., bile acid sequestrants, ezetimibe, PCSK9 inhibitors, bempedoic acid, inclisiran). According to ACC, patients without clinical ASCVD with baseline LDL cholesterol concentrations greater than 190 mg/dL not due to secondary causes may be considered for ezetimibe and/or a PCSK9 inhibitor if they have not met certain thresholds of LDL cholesterol reduction on maximally tolerated statin therapy.

Homozygous Familial Hypercholesterolemia

Used as an adjunct to other LDL-cholesterol-lowering therapies in adults with homozygous familial hypercholesterolemia (HoFH) to reduce LDL cholesterol concentrations. Designated an orphan drug by FDA for this use.

Current treatments for patients with HoFH and clinical ASCVD include lifestyle modifications (e.g., low-fat diet, maintenance of a healthy body weight, smoking cessation) and maximally tolerated dosages of statins. In patients with HoFH and ASCVD who do not achieve target reductions in LDL cholesterol with maximally tolerated doses of statins alone, ezetimibe and/or a PCSK9 inhibitor should be considered; other nonstatin options (e.g., bempedoic acid, inclisiran, evinacumab, lomitapide) may be considered if LDL cholesterol remains uncontrolled.

Alirocumab Dosage and Administration

General

Patient Monitoring

Assess low-density lipoprotein (LDL)-cholesterol when clinically appropriate. Alirocumab’s LDL-lowering effects can be measured as early as 4 weeks after initiation of treatment.
For patients receiving the every-4-week (i.e., once-monthly) alirocumab regimen, LDL-cholesterol concentrations should be measured just prior to the next scheduled dose since some patients may experience considerable variation in LDL-cholesterol concentrations during the monthly dosing interval.

Other General Considerations

Periodically reinforce adherence to lifestyle modifications. Antilipemic therapy is an adjunct to, not a substitute for, lifestyle modifications that reduce the risk of ASCVD.

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.

Prior to administration, allow prefilled pens to warm to room temperature for 30–40 minutes. Do not return drug to refrigerator once removed.

Inject into areas of thigh, abdomen (except for 2-inch area around the navel), or upper arm that are not tender, bruised, red, or indurated; rotate injection sites.

To administer a 300 mg dose of alirocumab, administer 2 consecutive doses of 150 mg at 2 different injection sites.

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, either 75 mg every 2 weeks or 300 mg every 4 weeks. May adjust dosage to 150 mg every 2 weeks if response is inadequate.

For patients receiving 300 mg every 4 weeks, reassess LDL cholesterol concentrations just prior to the next scheduled dose because LDL cholesterol concentrations can vary between doses in some patients.

Primary Hyperlipidemia (including Heterozygous Familial Hypercholesterolemia)

Sub-Q

Initially, either 75 mg every 2 weeks or 300 mg every 4 weeks. May adjust dosage to 150 mg every 2 weeks if response is inadequate.

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.

Homozygous Familial Hypercholesterolemia

Sub-Q

150 mg every 2 weeks. In patients undergoing LDL apheresis, may administer without regard to timing of the procedure.

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.

Cautions for Alirocumab

Contraindications

History of serious hypersensitivity reaction to alirocumab or any of its excipients.

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.

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. Monoclonal antibodies cross placenta in increasing amounts closer to term.

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

Report alirocumab exposure in pregnancy at 1-844-743-6643.

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

Adverse effects (≥5%) in primary hyperlipidemia studies: nasopharyngitis, injection site reactions (e.g., erythema/redness, itching, swelling, pain/tenderness), influenza.

Adverse effects (≥5%) in patients with established cardiovascular disease: noncardiac chest pain, nasopharyngitis, myalgia.

Drug Interactions

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

Advise patients to read the manufacturer’s patient information and instructions for use prior to starting therapy and each time the prescription is refilled.
Advise patients to discontinue alirocumab and promptly seek medical attention if any signs or symptoms of serious hypersensitivity (e.g., severe pruritus, rash, or redness; swollen face; difficulty breathing) occur.
Instruct patients and/or caregivers regarding proper preparation and subcutaneous administration of alirocumab, including use of aseptic technique and safe disposal of the prefilled pens in a puncture-resistant container. Inform patients that injection of alirocumab may take up to 20 seconds.
Instruct patients on proper storage of the drug.
Instruct patients not to reuse the prefilled pens.
Advise patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed. Encourage women who become pregnant while receiving alirocumab to contact the pregnancy safety study.
Advise patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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