Skip to Content
Explore different treatments for your high cholesterol >

Praluent

Generic Name: Alirocumab
Class: Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Inhibitors
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

Introduction

Antilipemic agent; fully human monoclonal antibody to human proprotein convertase subtilisin kexin type 9 (PCSK9).1 2 3 4 7 10 11 12 17 19

Uses for Praluent

Primary Hypercholesterolemia

Adjunct to diet and maximally tolerated hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (i.e., statin) therapy in patients with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL-cholesterol concentrations.1 2 3 19 24 25

Further reduces LDL concentrations by approximately 40–60% when added to maximally tolerated statin therapy; however, effects on cardiovascular morbidity and mortality have not been established.1 9 18 19 22 23 24 26 32 34

Praluent Dosage and Administration

General

Monitor serum LDL-cholesterol concentrations to assess response to therapy and need for dosage adjustments.1

Administration

Sub-Q Administration

Administer by sub-Q injection once every 2 weeks.1

Injection may take up to 20 seconds to complete.1

Instruct patients on proper techniques for self-administration using prefilled pen or syringe provided by manufacturer.1 13 15 16 (See Advice to Patients.)

Prior to administration, allow prefilled pens and syringes to warm to room temperature for 30–40 minutes and use as soon as possible thereafter.1 15 16 Do not return drug to refrigerator once removed.15 16 (See Storage under Stability.)

Inject into thigh, abdomen (except for 2-inch area around the navel), or upper arm; rotate injection sites.1 15 16 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.1 15 16

Do not administer with other drugs at the same injection site.1

If a dose is missed, administer as soon as remembered within 7 days and then resume regular dosing schedule (i.e., administer next dose 2 weeks from the day of the missed dose).1 If missed dose is not administered within 7 days, skip the dose and resume regular dosing schedule.1

Contains no preservatives; intended for single use only.1

Dosage

Adults

Primary Hypercholesterolemia
Patients with Heterozygous Familial Hypercholesterolemia or Clinical ASCVD
Sub-Q

Initially, 75 mg every 2 weeks.1

May increase to 150 mg every 2 weeks if response is inadequate.1

Monitor serum LDL-cholesterol concentrations within 4–8 weeks of initiating or titrating therapy and adjust dosage accordingly.1

Prescribing Limits

Adults

Primary Hypercholesterolemia
Patients with Heterozygous Familial Hypercholesterolemia or Clinical ASCVD
Sub-Q

150 mg every 2 weeks.1

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: No dosage adjustment necessary.1

Severe hepatic impairment: Data are lacking.1

Renal Impairment

Mild or moderate renal impairment: No dosage adjustment necessary.1

Severe hepatic impairment: Data are lacking.1

Geriatric Patients

No specific dosage recommendations.1

Other Special Populations

Dosage adjustments based on age, body weight, gender, or race not required.1

Cautions for Praluent

Contraindications

  • History of serious hypersensitivity reaction to alirocumab.1 (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.1 18

If a serious hypersensitivity reaction occurs, discontinue drug and initiate standard of care treatment; monitor patient until signs and symptoms resolve.1 (See Contraindications under Cautions.)

Immunogenicity

Development of anti-alirocumab antibodies reported, some of which were neutralizing.1 A higher incidence of injection site reactions observed in antibody-positive patients.1 Some patients who developed neutralizing antibodies exhibited a transient or prolonged loss of efficacy.1

Long-term effects of continued alirocumab therapy in the presence of such antibodies not known.1

Specific Populations

Pregnancy

No adequate and well-controlled studies of alirocumab in pregnant women.1 Weigh potential benefits versus possible risk to fetus.1

Adverse embryofetal effects not observed in animal studies with alirocumab; however, some evidence of humoral immune suppression demonstrated in infant monkeys exposed to the drug in utero.1

Lactation

Not known whether distributed into human milk.1 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.1

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.1

Pediatric Use

Safety and efficacy not established.1

Geriatric Use

No overall differences in efficacy or safety relative to younger adults; however, possibility of increased sensitivity cannot be ruled out.1

Hepatic Impairment

Pharmacokinetics of alirocumab not substantially altered by mild or moderate hepatic impairment.1

Safety and efficacy not established in patients with severe hepatic impairment.1

Renal Impairment

Renal function not expected to affect pharmacokinetics of alirocumab.1

Safety and efficacy not established in patients with severe renal impairment.1

Common Adverse Effects

Nasopharyngitis,1 3 injection site reactions (e.g., erythema/redness, itching, swelling, pain/tenderness),1 2 3 influenza,1 urinary tract infection,1 3 diarrhea,1 bronchitis,1 myalgia,1 2 muscle spasms,1 sinusitis,1 3 cough,1 contusion,1 musculoskeletal pain.1

Very low levels of LDL cholesterol (e.g., <25 mg/dL) occurred in clinical studies.1 32 Although adverse consequences were not identified, long-term effects not known.1

Interactions for Praluent

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).1

Drugs Metabolized by Hepatic Microsomal Enzymes

CYP substrates: Pharmacokinetic interactions unlikely.1

Drugs Affected by Transport Systems

Substrates of P-gp or OATP: Pharmacokinetic interactions unlikely.1

Specific Drugs

Drug

Interaction

Comments

HMG-CoA reductase inhibitors (statins)

Decreased half-life of alirocumab to 12 days; however, not clinically important1

Atorvastatin: No clinically important changes in the statin concentration observed1

Rosuvastatin: No clinically important changes in the statin concentration observed1

No dosage adjustments necessary1

Praluent Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability approximately 85% after sub-Q injection.1

Onset

Following sub-Q administration, maximal suppression of free PCSK9 occurs within 4–8 hours.1 In healthy individuals, maximal reduction in LDL-cholesterol concentrations observed 15 days after injection.10

Plasma Concentrations

Peak plasma concentrations achieved in 3–7 days.1 10

Slightly greater than dose-proportional increases in plasma concentration observed with increased doses.1

Steady-state concentrations achieved after 2–3 doses; accumulation ratio approximately twofold.1

Distribution

Extent

Distributed principally into circulatory system.1

Crosses the placenta.1

Not known whether distributed into milk.1

Elimination

Metabolism

Expected to be degraded into small peptides and individual amino acids.1

Elimination Route

At low concentrations, elimination occurs principally through saturable binding to the PCSK9 target.1

At high concentrations, elimination occurs principally through a nonsaturable proteolytic pathway.1

Half-life

Approximately 17–20 days.1

Stability

Storage

Parenteral

Solution for Injection

2–8°C.1 Store in original carton to protect from light.1 Do not shake, freeze, or expose to extreme heat or direct sunlight.1 15 16

Use within 24 hours after removal from refrigeration.1

Actions

  • Fully human IgG1 monoclonal antibody that binds to PCSK9.1 2 3 4 7 10 11 12 17 19 Produced by recombinant DNA technology.1

  • PCSK9 is a serine protease produced principally in the liver.7 9 11 12 Major function of PCSK9 is to promote degradation of LDL receptors, the primary receptors responsible for clearing circulating LDL cholesterol.1 9 11 25

  • 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.1 7 10 17

  • Reductions in lipoprotein (a), apolipoprotein B, and other lipid fractions also demonstrated.1 2 3 24 32

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.1 13 15 16

  • 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.1 13 (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 and syringes in a puncture-resistant container.1 13 Importance of informing patients that injection of alirocumab may take up to 20 seconds.1

  • Importance of instructing patients on proper storage of the drug.1

  • Importance of instructing patients not to reuse the prefilled pens and syringes.1

  • 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.1 13

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 13 (See Pregnancy in Cautions.)

  • Importance of informing patients of other important precautionary information.1 (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 and syringes)

Sanofi-Aventis and Regeneron

150 mg/mL

Praluent (available as single-dose prefilled injection pens and syringes)

Sanofi-Aventis and Regeneron

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814. Review Date: September 06, 2016.

References

1. Sanofi-Aventis U.S. LLC. Praluent (alirocumab) injection prescribing information. Bridgewater, NJ; 2015 Jul.

2. Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372:1489-99. [PubMed 25773378]

3. Kereiakes DJ, Robinson JG, Cannon CP et al. Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study. Am Heart J. 2015; 169:906-915.e13. [PubMed 26027630]

4. Kastelein JJ, Robinson JG, Farnier M et al. Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia not adequately controlled with current lipid-lowering therapy: design and rationale of the ODYSSEY FH studies. Cardiovasc Drugs Ther. 2014; 28:281-9. [PubMed 24842558]

5. . Risk of fatal coronary heart disease in familial hypercholesterolaemia. Scientific Steering Committee on behalf of the Simon Broome Register Group. BMJ. 1991; 303:893-6. [PubMed 1933004]

6. World Health Organization. Familial hypercholesterolemia (FH): report of a second WHO consultation. Geneva: World Health Organization; 1998.

7. Reiner Z. Management of patients with familial hypercholesterolaemia. Nat Rev Cardiol. 2015; 12:565-75. [PubMed 26076948]

8. Ito MK, McGowan MP, Moriarty PM et al. Management of familial hypercholesterolemias in adult patients: recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia. J Clin Lipidol. 2011; 5(3 Suppl):S38-45. [PubMed 21600528]

9. Okere AN, Serra C. Evaluation of the Potential Role of Alirocumab in the Management of Hypercholesterolemia in Patients with High-Risk Cardiovascular Disease. Pharmacotherapy. 2015; 35:771-9. [PubMed 26256279]

10. Lunven C, Paehler T, Poitiers F et al. A randomized study of the relative pharmacokinetics, pharmacodynamics, and safety of alirocumab, a fully human monoclonal antibody to PCSK9, after single subcutaneous administration at three different injection sites in healthy subjects. Cardiovasc Ther. 2014; 32:297-301. [PubMed 25256660]

11. Farnier M. PCSK9: From discovery to therapeutic applications. Arch Cardiovasc Dis. 2014; 107:58-66. [PubMed 24373748]

12. Gouni-Berthold I, Berthold HK. PCSK9 antibodies for the treatment of hypercholesterolemia. Nutrients. 2014; 6:5517-33. [PubMed 25470376]

13. Sanofi-Aventis U.S. LLC. Praluent (alirocumab) injection patient information. Bridgewater, NJ; 2015 Jul.

15. Sanofi-Aventis U.S. LLC. Praluent (alirocumab) injection single-dose pre-filled pen (75 mg/mL or 150 mg/mL) instructions for use. Bridgewater, NJ; 2015 Jul.

16. Sanofi-Aventis U.S. LLC. Praluent (alirocumab) injection single-dose pre-filled syringe (75 mg/mL or 150 mg/mL) instructions for use. Bridgewater, NJ; 2015 Jul.

17. Kühnast S, van der Hoorn JW, Pieterman EJ et al. Alirocumab inhibits atherosclerosis, improves the plaque morphology, and enhances the effects of a statin. J Lipid Res. 2014; 55:2103-12. [PubMed 25139399]

18. US Food and Drug Administration. Summary Review: BLA# 125559. From FDA website.

19. . Alirocumab (Praluent) to lower LDL-Cholesterol. Med Lett Drugs Ther. 2015; 57:113-5. [PubMed 26262881]

20. European Association for Cardiovascular Prevention & Rehabilitation, Reiner Z, Catapano AL et al. ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011; 32:1769-818. [PubMed 21712404]

21. Schwartz GG, Bessac L, Berdan LG et al. Effect of alirocumab, a monoclonal antibody to PCSK9, on long-term cardiovascular outcomes following acute coronary syndromes: rationale and design of the ODYSSEY outcomes trial. Am Heart J. 2014; 168:682-9. [PubMed 25440796]

22. Everett BM, Smith RJ, Hiatt WR. Reducing LDL with PCSK9 Inhibitors--The Clinical Benefit of Lipid Drugs. N Engl J Med. 2015; 373:1588-91. [PubMed 26444323]

23. White CM. Therapeutic Potential and Critical Analysis of the PCSK9 Monoclonal Antibodies Evolocumab and Alirocumab. Ann Pharmacother. 2015; 49:1327-35. [PubMed 26424774]

24. Kastelein JJ, Ginsberg HN, Langslet G et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015; 36:2996-3003. [PubMed 26330422]

25. Markham A. Alirocumab: First Global Approval. Drugs. 2015; 75:1699-705. [PubMed 26370210]

26. Doggrell SA, Lynch KA. Is there enough evidence with evolocumab and alirocumab (antibodies to proprotein convertase substilisin-kexin type, PCSK9) on cardiovascular outcomes to use them widely? Evaluation of Sabatine MS, Giugliano RP, Wiviott SD et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1500-1509, and Robinson JG, Farnier M, Krempf M et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med 2015;372:1488-99. Expert Opin Biol Ther. 2015; :1-5. [PubMed 26414456]

30. Cannon CP, Blazing MA, Giugliano RP et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015; 372:2387-97. [PubMed 26039521]

31. Navarese EP, Kolodziejczak M, Schulze V et al. Effects of Proprotein Convertase Subtilisin/Kexin Type 9 Antibodies in Adults With Hypercholesterolemia: A Systematic Review and Meta-analysis. Ann Intern Med. 2015; 163:40-51. [PubMed 25915661]

32. Reviewers' comments (personal observations) on alirocumab.

34. Sanofi-aventis. Bridgewater, NJ: Personal Communication.

248. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults: Adult Treatment Panel III Report. From AHA web site.

269. Grundy SM, Cleeman JI, Bairey Merz CN et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004; 110: 227-39.

350. Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63:2889-934. [PubMed 24239923]

352. Eckel RH, Jakicic JM, Ard JD et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014; 63:2960-84. [PubMed 24239922]

Hide