Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution Auto-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]
Pharmacology
Mechanism of Action
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.
Pharmacokinetics/Pharmacodynamics
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, alone or in combination with other lipid-lowering therapies (eg, statins, ezetimibe) for the treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia [HeFH]) to reduce low-density lipoprotein cholesterol (LDL-C).
Secondary prevention of cardiovascular events: To reduce the risk of MI, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease (Schwartz 2018).
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.
Dosage and Administration
Dosing: Adult
Note: Use may be considered in patients who do not meet cholesterol treatment goals with dietary modification and other lipid-lowering therapies (ie, maximally tolerated statin plus ezetimibe) (AHA/ACC [Grundy 2018]).
Hyperlipidemia, primary: SubQ: Initial: 75 mg once every 2 weeks or 300 mg once 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. Note: In patients with heterozygous familial hypercholesterolemia undergoing LDL apheresis, the recommended initial dose is 150 mg once every 2 weeks.
Secondary prevention of cardiovascular events: SubQ: Initial: 75 mg once every 2 weeks or 300 mg once every 4 weeks; for both regimens, if an adequate LDL-C response is not achieved, may increase or modify dosing regimen to a maximum dose 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.
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. For patients undergoing LDL apheresis, may be administered without regard to the timing of apheresis.
Storage
Store at 2°C to 8°C (36°F to 46°F) in the outer carton to protect from light. If needed, solution may be kept at room temperature up to 25°C (77°F) for a maximum of 30 days in original carton to protect from light. Do not store >25°C (>77°F). After removal from the refrigerator, solution must be used within 30 days or discarded. Do not freeze. Do not expose to extreme heat. Do not shake.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
>10%: Local: Injection site reaction (4% to 17%)
1% to 10%:
Gastrointestinal: Diarrhea (5%)
Hematologic & oncologic: Bruise (2%)
Hepatic: Liver enzyme disorder (3%), increased serum transaminases (>3 x ULN: 2%)
Hypersensitivity: Hypersensitivity reaction (9%)
Immunologic: Antibody development (6%; neutralizing: <1%)
Infection: Influenza (6%)
Neuromuscular & skeletal: Myalgia (4% to 6%), muscle spasm (3%)
Respiratory: Cough (3%)
Frequency not defined:
Cardiovascular: Hypersensitivity angiitis
Endocrine & metabolic: Decreased LDL cholesterol (<25 mg/dL)
<1%, postmarketing, and/or case reports: Angioedema, flu-like symptoms
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
Lipid profile (fasting or nonfasting) before initiating treatment. Fasting lipid profile should be rechecked 4 to 12 weeks after starting therapy and every 3 to 12 months thereafter (AHA/ACC [Grundy 2018]). 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
Pregnancy Considerations
Alirocumab is a humanized monoclonal antibody (IgG1). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).
Health care providers are encouraged to enroll women exposed to alirocumab during pregnancy in the MotherToBaby Pregnancy Studies by contacting the Organization of Teratology Information Specialists (OTIS) (877-311-8972).
Patient Education
What is this drug used for?
- It is used to lower cholesterol.
- It is used to lower the risk of heart attack, stroke, and a type of chest pain (unstable angina) in people with heart disease.
Frequently reported side effects of this drug
- Stuffy nose
- Sore throat
- Injection site pain
- Itching or irritation
- Flu-like symptoms
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
