Generic Name

Evolocumab

Mechanism

• Selective PCSK9 inhibition: binds circulating PCSK9 and prevents it from binding to LDL‑receptor (LDLR) on hepatocytes.
• Receptor recycling: preserves LDLR on the hepatocyte surface, increasing clearance of LDL‑C from plasma.
• Result: significant reduction in LDL‑C levels (≈45‑60 % with standard dosing) and a modest decline in other atherogenic lipids.

Pharmacokinetics

Indications

• Heterozygous familial hypercholesterolemia (HeFH) or homozygous FH with LDL‑C levels that remain above target despite maximally tolerated statin therapy.
• Statin‑tolerant patients with atherosclerotic cardiovascular disease (ASCVD) requiring LDL‑C reduction.
• Post‑acute coronary syndrome (ACS) patients as part of intensive lipid‑lowering strategy.
• CMC guidelines support Evolocumab for high‑risk ASCVD patients who do not achieve LDL‑C goals with standard therapies.

Contraindications

• Known hypersensitivity to Evolocumab or any of its excipients.
• Pregnancy/Lactation: Not recommended; data insufficient.
• Active infection: Particularly in patients with severe inflammation (antibody‑mediated).
• Immunocompromised patients: Monitor for infections; not contraindicated but warrants caution.

Warnings
• Immunogenicity: rare anti‑drug antibodies may reduce efficacy.
• Injection‑site reactions: can occur; educate on rotation sites.

Dosing

• Standard regimen:
• 75 mg subcutaneously every 2 weeks, or
• 150 mg subcutaneously every 4 weeks.
• Initiation: first dose via health‑care professional; thereafter patient self‑injects at home.
• Supplement: May be given with maximally tolerated statins or ezetimibe to maximize LDL‑C reduction.
• Dose adjustment: Not routinely needed; adjust if significant LDL‑C decline occurs without adverse effects.

Adverse Effects

• Common (≥10 %)
• Upper respiratory tract infection
• Injection‑site reaction (rash, erythema, pain)
• Headache, nasopharyngitis
• Serious
• Hypersensitivity reactions (anaphylaxis)
• Severe infections (case reports of invasive bacterial infections)
• Amyloidosis (very rare)
• Rare
• Autoimmune disorders (e.g., lupus‑like syndrome)
• Livedo reticularis

Monitoring

• Baseline & periodic lipid panels: LDL‑C, HDL‑C, total cholesterol, triglycerides.
• Liver function tests: ALT/AST, occasionally bilirubin.
• Anti‑drug antibodies: In patients with loss of response.
• Routine labs: CBC, serum creatinine to monitor overall health and compliance.
• Clinical: Record injection‑site reactions, signs of infection, or allergic symptoms.

Clinical Pearls

• “When the Statin Falls Short”: If LDL‑C remains >100 mg/dL after high‑dose statin plus ezetimibe, add Evolocumab to achieve >50 % LDL‑C reduction.
• “Dose Flexibility”: Patients who miss a 2‑week dose can simply advance the next dose; a 4‑week interval is acceptable.
• “Injecting at Home”: Teach proper subcutaneous technique—use pre‑filled 3 mL syringes, clean the skin, and rotate arm/leg sites.
• “Pregnancy Counseling”: Discuss risk/benefit; drug is not metabolized like small molecules but caution remains until more safety data is available.
• “Drug‑Drug Interaction”: No significant interactions; clearance is via proteolysis, not CYP enzymes.
• “Adherence Boost”: Align dosing with other medications; set reminders to help patients maintain a strict schedule.

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