Alirocumab

1. Drug Name

• Generic Name: Alirocumab

• Brand Name: Praluent

2. Drug Classification

• Class: Antihyperlipidemic agent

• Subclass: PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitor

3. Mechanism of Action

• Inhibition of PCSK9: Alirocumab is a monoclonal antibody that binds to PCSK9, a protein that degrades LDL receptors on liver cells. By inhibiting PCSK9, alirocumab increases the availability of LDL receptors on hepatocyte surfaces, enhancing the uptake and clearance of LDL cholesterol from the bloodstream.

• Effect on Lipid Profile: This mechanism results in substantial reductions in LDL cholesterol levels, and moderate reductions in total cholesterol and apolipoprotein B.

4. Pharmacokinetics

• Absorption:

  • Bioavailability: Approximately 85% following subcutaneous injection.

  • Time to Peak: Peaks at 3-7 days post-injection.

• Distribution:

  • Protein Binding: As a monoclonal antibody, binds specifically to PCSK9; volume of distribution is low.

• Metabolism:

  • Primarily degraded by nonspecific proteolysis as a monoclonal antibody.

• Excretion:

  • Half-Life: Ranges between 17 to 20 days, depending on dose and LDL receptor expression.

• Special Populations:

  • Hepatic/Renal Impairment: No specific adjustments recommended; however, clearance may be altered in hepatic dysfunction.

5. Indications

• Primary Indications:

  • Primary Hyperlipidemia: Adjunct to diet and statins for patients with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who need additional LDL reduction.

• Off-Label Uses: Occasionally used in severe cases of hypercholesterolemia when statins are contraindicated.

6. Dosage and Administration

• Adult Dosage: Initial dose is typically 75 mg subcutaneously every 2 weeks, or 300 mg once a month. Dosage may be adjusted up to 150 mg every 2 weeks for additional LDL reduction.

• Administration: Subcutaneous injection in the thigh, abdomen, or upper arm.

• Renal/Hepatic Adjustment: No dose adjustments recommended for mild to moderate renal or hepatic impairment.

7. Contraindications

• Absolute Contraindications:

  • Known hypersensitivity to alirocumab or any component of the formulation.

• Relative Contraindications:

  • Severe hepatic impairment due to unknown safety and efficacy in this population.

8. Warnings and Precautions

• Hypersensitivity Reactions: Rare cases of allergic reactions, including vasculitis and hypersensitivity requiring medical attention.

• Injection Site Reactions: Localized pain, erythema, and swelling are possible, usually mild to moderate.

• Neurocognitive Effects: Some studies have noted a mild increase in neurocognitive symptoms such as memory loss and confusion; monitoring is suggested for patients with a history of cognitive impairment.

9. Adverse Effects

• Common:

  • Injection Site Reactions: Pain, erythema, swelling.

  • Flu-like Symptoms: Nasopharyngitis, upper respiratory tract infection.

• Less Common but Significant:

  • Hypersensitivity Reactions: Rash, pruritus, and allergic vasculitis.

• Serious Adverse Effects:

  • Neurocognitive Impairment: Rare cases of confusion and memory disturbance.

10. Drug Interactions

• Statins: No clinically significant interactions, but commonly co-administered for synergistic LDL lowering.

• CYP450 Involvement: Not metabolized via CYP enzymes, reducing the risk of drug-drug interactions.

11. Clinical Pharmacology

• Pharmacodynamics: Alirocumab’s lipid-lowering effects are mediated through PCSK9 inhibition, specifically increasing hepatic LDL receptor availability.

• Effects Beyond LDL: Minimal effects on HDL cholesterol and triglycerides; primarily LDL reduction.

12. Special Populations

• Pregnancy: Classified as Category B; limited data available, so use only if the potential benefit justifies the potential risk.

• Lactation: Unknown if excreted in human milk; caution advised.

• Geriatrics: No dosage adjustments necessary.

• Pediatrics: Safety and efficacy have not been established.

• Renal and Hepatic Impairment: Generally well-tolerated, but use with caution in severe hepatic disease.

13. Therapeutic Uses

• Hyperlipidemia Management: Effective as an adjunct to statin therapy or as monotherapy in cases of statin intolerance.

• ASCVD Risk Reduction: Approved for patients with clinical ASCVD needing additional LDL lowering despite statin use.

• Heterozygous Familial Hypercholesterolemia (HeFH): A key treatment option when LDL levels remain elevated despite conventional therapy.

14. Monitoring and Follow-Up

• Lipid Panel: Regular lipid panel monitoring every 4-6 weeks during dose adjustments and routinely every 6-12 months thereafter.

• Hypersensitivity Monitoring: Observe for signs of allergic reactions, especially after initial doses.

• Neurocognitive Status: Routine cognitive assessments are not necessary but monitor if the patient reports new or worsening cognitive symptoms.

15. Overdose Management

• Symptoms: No specific overdose symptoms identified due to the high therapeutic index.

• Management: Supportive care; monitor for adverse effects and manage symptomatically if necessary.

16. Patient Counseling Information

• Administration: Teach patients proper subcutaneous injection techniques and rotating injection sites to minimize irritation.

• Potential Side Effects: Advise patients about possible injection site reactions and flu-like symptoms.

• Storage: Store in the refrigerator and protect from light; bring to room temperature before injection to reduce discomfort.

• Regular Follow-Up: Stress the importance of regular follow-up visits for lipid panel checks and to discuss any new symptoms.