General

Pronunciation:
a-li-roe-kyoo-mab

Trade Name(s)

• Praluent

Ther. Class.

lipid-lowering agents

Pharm. Class.

proprotein convertase subtilisin kexin type9 pcsk9 inhibitors

monoclonal antibodies

Indications

• Primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) (as adjunct to diet, as monotherapy, or in combination with other low-density lipoprotein cholesterol [LDL-C]–lowering therapies).
• Reduction in risk of MI, stroke, and unstable angina requiring hospitalization in patients with established cardiovascular disease.
• Homozygous familial hypercholesterolemia (HoFH) (as adjunct to other LDL-C lowering therapies).
• HeFH in children ≥8 yr (as adjunct to diet and other LDL-C-lowering therapies).

Action

A human monoclonal immunoglobulin (IgG1) produced in genetically engineered Chinese hamster ovary cells that binds to PCSK9, inhibiting its binding to the low-density lipoprotein receptor (LDLR) resulting in ↑ number of LDLRs available to clear LDL from blood.

Therapeutic Effect(s):

• Reduction in LDL-C in primary hyperlipidemia, HoFH, and HeFH.
• Reduction in risk of MI, stroke, and unstable angina requiring hospitalization.

Pharmacokinetics

Absorption: Well absorbed (85%) following SUBQ administration.

Distribution: Mostly distributed in the circulatory system.

Metabolism and Excretion: Eliminated by binding to PCSK9 and by proteolytic degradation.

Half-life: 17–20 days.

TIME/ACTION PROFILE (effect on circulating unbound PCSK9)

Contraindication/Precautions

Contraindicated in:

• Serious hypersensitivity.

Use Cautiously in:

• Severe renal impairment;
• Severe hepatic impairment;
• OB:  Safety not established in pregnancy;
• Lactation: Safety not established in breastfeeding;
• Pedi:  Safety and effectiveness not established in children <8 yr (HeFH) or <18 yr (other types of hyperlipidemia);
• Geri:  Older adults may be more sensitive to drug effects.

Adverse Reactions/Side Effects

Local: injection site reactions

Neuro: confusion

Misc: HYPERSENSITIVITY REACTIONS (including angioedema, vasculitis)

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

None reported.

Route/Dosage

Primary Hyperlipidemia (Including Heterozygous Familial Hypercholesterolemia) or Established Cardiovascular Disease

SUBQ (Adults): 75 mg every 2 wk  or  300 mg every 4 wk; if desired LDL-C has not been achieved, may ↑ dose to 150 mg every 2 wk.  Patients with HeFH undergoing apheresis:  150 mg every 2 wk.

Homozygous Familial Hypercholesterolemia

SUBQ (Adults): 150 mg every 2 wk.

Heterozygous Familial Hypercholesterolemia

SUBQ (Children 8–17 yr and ≥50 kg): 300 mg every 4 wk; if desired LDL-C has not been achieved, may ↑ dose to 150 mg every 2 wk. .

SUBQ (Children 8–17 yr and <50 kg): 150 mg every 4 wk; if desired LDL-C has not been achieved, may ↑ dose to 75 mg every 2 wk. .

Availability

Solution for injection (prefilled pens): 75 mg/mL, 150 mg/mL

Assessment

• Obtain a diet history, especially with regard to fat consumption.
• Monitor for signs and symptoms of hypersensitivity reactions (pruritus, rash, urticaria, hypersensitivity vasculitis, and hypersensitivity reactions requiring hospitalization) during therapy. If severe symptoms occur, discontinue alirocumab.

Lab Test Considerations:

Assess LDL-C levels within 4–8 wk of initiating or titrating alirocumab for patients taking every 2 wk or just before next dose for patients taking every 4 wk, to assess response and adjust dose, if needed.

Implementation

• SUBQ Allow solution to warm to room temperature for 30–40 min before injecting. May be kept at room temperature for up to 30 days. Solution is clear and colorless to pale yellow; do not administer solutions that are cloudy or contain particulate matter. Do not shake. Inject into thigh, abdomen, or upper arm into areas not tender, bruised, red, or indurated. Rotate sites with each injection. Do not inject into areas with skin disease or injury (sunburns, rashes, inflammation, skin infections). Do not reuse prefilled pen or syringe. Do not administer other injectable drugs at same site. Store in refrigerator; keep in original container; protect from light. Do not freeze.
  • Administer 300 mg dose as two 150 mg injections in 2 different sites.

Patient/Family Teaching

• Instruct patient in correct technique for self-injection and care and disposal of equipment. Administer missed doses within 7 days; then resume original schedule. If not administered within 7 days, wait until next dose on original schedule. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
• Advise patient that this medication should be used in conjunction with diet restrictions (fat, cholesterol, carbohydrates, alcohol), exercise, and cessation of smoking.
• Advise patient to notify health care professional immediately if signs and symptoms of hypersensitivity reactions occur.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products.
• Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
• Rep:  Advise patient to notify health care professional if pregnancy is planned or suspected or if breastfeeding. There is a pregnancy safety study for alirocumab. If alirocumab is administered during pregnancy, report alirocumab exposure by contacting Regeneron at 1-844-734-6643.

Evaluation/Desired Outcomes

• ↓ LDL-C levels.
• Reduction in risk of MI, stroke, and unstable angina requiring hospitalization.