Introduction
Praluent (alirocumab) is a fully human monoclonal antibody belonging to the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor class of lipid-lowering agents. Developed by Sanofi and Regeneron Pharmaceuticals, it received FDA approval in 2015 as an adjunct to diet and maximally tolerated statin therapy for patients requiring additional LDL cholesterol reduction. Praluent represents a significant advancement in the management of hypercholesterolemia, particularly for patients who cannot achieve target LDL-C levels with conventional therapies.
Mechanism of Action
Praluent binds selectively and with high affinity to PCSK9, a protein that promotes degradation of LDL receptors on hepatocyte surfaces. By inhibiting the interaction between PCSK9 and LDL receptors, Praluent increases the number of available LDL receptors, enhancing hepatic uptake of LDL cholesterol from the bloodstream. This mechanism results in significant reductions in circulating LDL-C, apolipoprotein B, and lipoprotein(a) levels.
Indications
- Primary hyperlipidemia: As an adjunct to diet, alone or in combination with other lipid-lowering therapies, in adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) to reduce LDL-C
- Heterozygous familial hypercholesterolemia (HeFH): To reduce LDL-C in pediatric patients aged 8 years and older with HeFH
- Cardiovascular risk reduction: To reduce the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease
Dosage and Administration
Standard dosing: 75 mg administered subcutaneously every 2 weeks Dose adjustment: May increase to 150 mg every 2 weeks if LDL-C response is inadequate Administration: Subcutaneous injection in the thigh, abdomen, or upper arm Special populations:- Renal impairment: No dose adjustment necessary
- Hepatic impairment: Use with caution in moderate to severe impairment
- Pediatric: 75 mg every 2 weeks for children ≥8 years with HeFH (may increase to 150 mg if needed)
- Geriatric: No dose adjustment required
Pharmacokinetics
Absorption: Peak plasma concentrations achieved in 3-7 days after subcutaneous administration Distribution: Volume of distribution approximately 0.04-0.05 L/kg Metabolism: Degraded via proteolytic enzymes to small peptides and amino acids Elimination: Half-life of 17-20 days; clearance occurs primarily via intracellular catabolism Bioavailability: Approximately 85% following subcutaneous administrationContraindications
- History of serious hypersensitivity reaction to alirocumab or any component of the formulation
- Active hepatic disease or unexplained persistent elevations in serum transaminases
Warnings and Precautions
- Hypersensitivity reactions: Including pruritus, rash, urticaria, and rarely, anaphylaxis
- Hepatic effects: Monitor liver function tests before initiation and during therapy
- Neurocognitive effects: Reports of neurocognitive adverse reactions in clinical trials
- Fetal risk: Based on animal studies, may cause fetal harm; advise women of reproductive potential
- Immunogenicity: Potential for anti-drug antibody development
Drug Interactions
- No clinically significant pharmacokinetic interactions with commonly co-administered drugs including statins, warfarin, or oral contraceptives
- Theoretical potential for reduced efficacy when administered with other PCSK9 inhibitors (concomitant use not recommended)
- Monitor lipid levels when adding or discontinuing other lipid-lowering therapies
Adverse Effects
Most common (≥5%):- Injection site reactions (redness, itching, swelling)
- Nasopharyngitis
- Influenza
- Urinary tract infections
- Hypersensitivity reactions
- Neurocognitive disorders
- Hepatic enzyme elevations
- Allergic conditions (eczema, allergic rhinitis)
Monitoring Parameters
- Baseline: Lipid profile, liver function tests (ALT, AST)
- Ongoing: LDL-C levels 4-8 weeks after initiation or dose adjustment
- Quarterly: Lipid panel until goals achieved, then every 6-12 months
- Periodic: Liver function tests, assessment for neurocognitive changes
- Continuous: Monitoring for injection site reactions and hypersensitivity
Patient Education
- Proper technique for subcutaneous injection and rotation of injection sites
- Importance of adherence to prescribed dosing schedule
- Continue dietary modifications and other lipid-lowering therapies as prescribed
- Recognize and report signs of hypersensitivity reactions
- Inform healthcare providers of all medications being taken
- Report any unusual cognitive changes or memory problems
- Store medication in original carton in refrigerator (2°C to 8°C)
- Do not freeze or shake the medication
- Allow prefilled pen or syringe to reach room temperature for 30-40 minutes before injection
References
1. FDA Prescribing Information: Praluent (alirocumab). 2023 2. Robinson JG, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499 3. Schwartz GG, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379(22):2097-2107 4. Ray KK, et al. Long-term efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolemia. J Clin Lipidol. 2020;14(2):154-165 5. Stroes ES, et al. PCSK9 inhibitors in clinical practice: Delivering on the promise? Atherosclerosis. 2021;321:90-96 6. American College of Cardiology/American Heart Association Guideline on the Management of Blood Cholesterol. 2018 7. European Society of Cardiology/European Atherosclerosis Society Guidelines for the management of dyslipidaemias. 2019