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Alirocumab

Pronunciation

(al i ROK ue mab)

Index Terms

  • REGN727
  • SAR236553

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Pen-injector, Subcutaneous [preservative free]:

Praluent: 75 mg/mL (1 mL); 150 mg/mL (1 mL) [contains mouse (murine) and/or hamster protein]

Solution Prefilled Syringe, Subcutaneous [preservative free]:

Praluent: 75 mg/mL (1 mL [DSC]); 150 mg/mL (1 mL [DSC]) [contains mouse (murine) and/or hamster protein]

Brand Names: U.S.

  • Praluent

Pharmacologic Category

  • Antilipemic Agent, PCSK9 Inhibitor
  • Monoclonal Antibody

Pharmacology

Alirocumab is a human monoclonal antibody (IgG1isotype) that binds to proprotein convertase subtilisin kexin type 9 (PCSK9). PCSK9 binds to the low-density lipoprotein receptors (LDLR) on hepatocyte surfaces to promote LDLR degradation within the liver. LDLR is the primary receptor that clears circulating LDL; therefore, the decrease in LDLR levels by PCSK9 results in higher blood levels of LDL-C. By inhibiting the binding of PCSK9 to LDLR, alirocumab increases the number of LDLRs available to clear LDL, thereby lowering LDL-C levels.

Distribution

IV: Vd: ~0.04 to 0.05 L/kg

Metabolism

Expected to undergo proteolysis and be degraded to small peptides and amino acids

Onset of Action

Peak effect: Proprotein convertase subtilisin kexin type 9 (PCSK9) suppression: 4 to 8 hours

Time to Peak

SubQ: 3 to 7 days

Half-Life Elimination

SubQ: Steady-state: 17 to 20 days; reduced to 12 days when administered with a statin

Use: Labeled Indications

Hyperlipidemia, primary: Adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease, who require additional lowering of LDL-C.

Limitation of use: The effect of alirocumab on cardiovascular morbidity and mortality has not been determined.

Contraindications

Serious hypersensitivity to alirocumab or any component of the formulation.

Documentation of allergenic cross-reactivity for PCSK9 inhibitors is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosing: Adult

Hyperlipidemia, primary: SubQ: Initial: 75 mg every 2 weeks or 300 mg every 4 weeks; for both regimens, if an adequate LDL-C response is not achieved, may increase or modify dosing regimen to a maximum of 150 mg every 2 weeks.

Switching regimens: When switching from the monthly regimen to an every 2 week regimen, start the new dose on the next scheduled dosing date; reassess LDL-C 4 to 8 weeks after dosing change.

Missed dose: If a dose is missed ≤7 days from the usual day of administration, administer the dose as soon as possible and then resume the original schedule; otherwise, if beyond 7 days, skip the missed dose and resume the normal dosing schedule, or if dosage is monthly, start a new schedule based on this date.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, dosage adjustment is unlikely to be required as monoclonal antibodies are not known to be renally eliminated.

Dosing: Hepatic Impairment

Mild to moderate impairment: No dosage adjustment necessary.

Severe impairment: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

Administration

SubQ: Allow solution to come to room temperature for 30 to 40 minutes prior to administration. Do not shake. Administer by subcutaneous injection into the thigh, abdomen, or upper arm; rotate injection site with each injection. For the 300 mg dose, administer two 150 mg injections consecutively at two different injection sites. Do not inject into areas of active skin disease or injury (eg, sunburns, skin rashes, inflammation, skin infections). Do not coadminister with other injectable drugs at the same injection site.

Storage

Store at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. Time out of refrigeration should not exceed 24 hours at 25°C (77°F). Do not freeze. Do not expose to extreme heat. Do not shake.

Drug Interactions

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Adverse Reactions

1% to 10%

Gastrointestinal: Diarrhea (5%)

Hepatic: Liver enzyme disorder (3%), increased serum transaminases (>3 X ULN; 2%)

Immunologic: Immunogenicity (5% to 6%; neutralizing: ≤1%; loss of efficacy: <1%)

Infection: Influenza (6%)

Local: Injection site reaction (7% to 17%)

Neuromuscular & skeletal: Myalgia (4%), muscle spasm (3%)

Respiratory: Cough (3%)

Frequency not defined: Endocrine & metabolic: Decreased LDL cholesterol (<25 mg/dL)

<1% (Limited to important or life-threatening): Confusion, hypersensitivity reaction (including hypersensitivity angiitis, pruritus, severe hypersensitivity, skin rash, urticaria), memory impairment

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions, including some severe reactions requiring hospitalization (eg, hypersensitivity vasculitis), have been reported. Discontinue treatment and initiate supportive treatment in patients who develop serious allergic reaction. Other hypersensitivity reactions, including pruritus, rash, and urticaria, have been reported.

Monitoring Parameters

LDL-C within 4 to 8 weeks of initiation or dose titration. For patients receiving 300 mg every 4 weeks, measure LDL-C just prior to the next scheduled dose (LDL-C varies considerably between doses with this regimen). Monitor for hypersensitivity reactions.

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies. Information specific to alirocumab in pregnancy is not available. However, IgG molecules are known to cross the placenta, with increasing amounts during the second and third trimesters of pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience rhinitis, pharyngitis, injection site pain, itching or irritation, or flu-like symptoms (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating, and advising patients.

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