Repatha
Repatha
Generic Name
Repatha
Mechanism
Repatha (alirocumab) is a fully human, monoclonal IgG₂ antibody that selectively binds proprotein convertase subtilisin/kexin type 9 (PCSK9). By neutralizing PCSK9, it prevents the proteolytic degradation of low‑density lipoprotein receptors (LDLR) on hepatocyte surfaces, thereby:
• Increasing LDL‑receptor recycling
• Enhancing hepatic clearance of LDL‑cholesterol (LDL‑C)
Result: a sustained 50–60 % reduction in LDL‑C when combined with statin therapy or as monotherapy in statin‑intolerant patients.
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Pharmacokinetics
| Property | Value | Notes |
| Route | Subcutaneous (SC)** | Typically 0.5 ml, pen‑injection |
| Absorption | 88–95 % bioavailability; peak serum concentration ~14 days post‑dose | Linear pharmacokinetics up to 300 mg |
| Half‑life | ~14–19 days | Supports q2w dosing |
| Volume of distribution | ≈ 17 L | Mirrors serum distribution of monoclonal antibodies |
| Clearance | ~0.5 ml day⁻¹ | Primarily target‑mediated disposition |
| Metabolism/Excretion | Proteolytic catabolism to peptides/amino acids | Minimal renal/hepatic elimination of unchanged drug |
*Key point:* The 2‑week interval is pharmacologically justified by nearly 90 % of the drug remaining in circulation after 14 days.
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Indications
- Heterozygous Familial Hypercholesterolemia (HeFH) with inadequate LDL‑C control on maximally tolerated statins or statin‑intolerant patients.
- Homozygous Familial Hypercholesterolemia (HoFH) (select patient subgroups).
- Secondary prevention in adults at very high cardiovascular risk who fail to achieve LDL‑C targets with maximally tolerated statins ± ezetimibe.
*Target LDL‑C goal:* < 1.4 mmol/L (55 mg/dL) for very high‑risk patients, < 1.8 mmol/L (70 mg/dL) for high‑risk.
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Contraindications
Contraindications
• Known hypersensitivity to alirocumab or any excipient.
• Active systemic infection or uncontrolled inflammatory disease.
Warnings
• Injection‑site reactions (pain, erythema, pruritus).
• Hypersensitivity reactions including anaphylaxis.
• Pregnancy/Lactation – Category C; avoid unless benefits outweigh risks.
• Liver Enzyme Elevation – monitor AST/ALT; rare hepatotoxicity reported.
• Rare PML – monitor for unexplained neurologic symptoms.
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Dosing
1. Starter dose: 75 mg every 2 weeks SC.
2. Titration: After 12 weeks, if LDL‑C > 1.8 mmol/L, increase to 150 mg q2w.
3. Maintenance: 150 mg q2w; dose may be altered to 75 mg q2w if LDL‑C target achieved earlier.
4. Route: Self‑administered SC injection (pre‑filled syringe or vial/pen; rotate sites).
5. Special Populations:
• Renal/ hepatic impairment: No dose adjustment required.
• Pediatrics (≥ 12 yrs): Approved dose 140 mg SC q1‑2 wk (US) or 75 mg q2w; monitor LDL‑C.
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Adverse Effects
| Category | Examples |
| Common | Injection‑site reactions, nasopharyngitis, muscle aches, headache, allergic contact dermatitis. |
| Serious | Anaphylactic reactions; eosinophilic pneumonia; serious hepatic events; rare severe cutaneous reactions (Stevens‑Johnson syndrome). |
| Laboratory | Elevated ALT/AST (≥ 3× ULN), mild hyperglycemia. |
*Action:* Report any allergic or severe reactions immediately; reassess liver function at screening and 12 weeks.
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Monitoring
- Baseline: CBC, CMP, lipid panel, liver enzymes, HbA1c.
- Follow‑up:
- Lipid panel *at 4–6 weeks* (to gauge response) and every 12 weeks thereafter.
- LFTs *at 12 weeks* and then annually (or sooner if clinically indicated).
- Injection‑site inspection at each visit.
- Risk‑Adjusted: For patients on concomitant anticoagulation, monitor INR if warfarin is used.
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Clinical Pearls
- Synergistic Statin Use: Achieve *maximally tolerated* statin dose before starting Repatha; combination increases LDL‑C reduction by ~85 %.
- Early Indication Works Best: Initiate therapy before LDL‑C rises ≥ 100 mg/dL to prevent atherosclerotic progression in HeFH.
- Dose Tailoring: If LDL‑C falls below 1.0 mmol/L (40 mg/dL), consider reducing to 75 mg q2w to mitigate injection‑site troubles while maintaining target.
- Lifestyle Punch‑through: Repatha is *not a substitute* for diet/exercise; counsel patients to continue Mediterranean‑style diets and regular aerobic activity.
- Ezetimibe Augmentation: Adding ezetimibe (10 mg daily) can reduce LDL‑C by ~15 %; useful when 150 mg q2w alone insufficient.
- Pregnancy Precautions: Repatha has no proven benefit in pregnancy; counsel on pregnancy planning.
- Vaccinations: No evidence contraindicating live vaccines; proceed as per routine schedule.
> Remember: Repatha is a *PCSK9 inhibitor* – a class that is distinctly different from statins and must be positioned as adjunctive therapy in evidence‑based lipid guidelines.
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