Praluent
Praluent
Generic Name
Praluent
Mechanism
- Inhibits PCSK9: Evolocumab binds circulating PCSK9, preventing its interaction with low‑density lipoprotein receptors (LDLR) on hepatocyte surfaces.
- Enhances LDL‑R recycling: By blocking PCSK9‑mediated LDLR degradation, the number of functional LDL receptors on the liver is increased, leading to accelerated clearance of LDL‑C from plasma.
- Potent LDL‑C reduction: Typical weekly or bi‑weekly subcutaneous dosing decreases LDL‑C by 50‑60% compared with baseline.
Pharmacokinetics
| Parameter | Typical Value (based on phase III data) |
| Absorption | Rapid, with peak serum concentrations 2–4 days post‑subcutaneous injection. |
| Distribution | Moderate volume of distribution (~15 L). Limited protein binding beyond PCSK9. |
| Metabolism | Proteolytic catabolism via normal antibody clearance pathways. Not metabolized by CYP enzymes. |
| Elimination | Linear clearance; mean half‑life ~14 days (supports bi‑weekly dosing). |
| Factors affecting PK | Body weight, renal/hepatic impairment have minimal impact; no dose adjustment needed. |
Indications
- Primary hypercholesterolemia (heterozygous familial hypercholesterolemia or mixed dyslipidemia) *in adults and children ≥18 y*.
- Heparin‑induced hyperlipidemia or LDL‑C lowering for atherosclerotic cardiovascular disease (ASCVD) when statins alone are insufficient or not tolerated.
- Adjunct therapy to statins, fibrates, nicotinic acid, ezetimibe, or bile acid sequestrants where ≥30% LDL‑C reduction is desired.
Contraindications
- Allergy to evolocumab or any component.
- Pregnancy and lactation: Not indicated; insufficient safety data.
- Adverse events: Severe hypersensitivity reactions (anaphylaxis) may require discontinuation.
- Cautions: Use with caution in patients with active infection, inflammatory disease, or those on systemic immunosuppressants due to potential immune modulation.
Dosing
| Regimen | Injection | Frequency | Notes |
| Initial | 140 mg SC | Weekly | For rapid LDL‑C lowering. |
| Maintenance | 140 mg SC | Bi‑weekly | Once sustained LDL‑C targets are achieved. |
| Weight‑based | 0.6 mg/kg SC | Bi‑weekly | Alternative dosing, particularly in children or extremes of body weight. |
• Administration technique: Subcutaneous injection into thigh or abdomen; rotate sites.
• Device: Pre‑filled syringe or autoinjector.
• Missed dose: If a scheduled dose is missed, take as soon as remembered; do not double‑dose.
Adverse Effects
Common (≥1 % incidence)
• Injection‑site reactions: pain, erythema, swelling, pruritus.
• Upper respiratory tract infections.
• Flu‑like symptoms: fever, myalgia.
• Headache.
Serious (rare)
• Hypersensitivity reactions (anaphylaxis, angioedema).
• Arthralgia (possible inflammatory arthritis).
• Infusion‑related reactions not typical due to SC route.
• Potential increased risk of depression or mood disorders observed in some trials – monitor patient mood.
Monitoring
| Parameter | Frequency | Rationale |
| Baseline & 6‑week LDL‑C | At initiation and 6 weeks | Target LDL‑C achievement. |
| Continued LDL‑C | Every 3–6 months | Long‑term efficacy. |
| Injection site inspection | Each visit | Detect cellulitis or abscess. |
| Renal & hepatic panels | Every 6–12 months | Although no dosage adjustment, assess overall health. |
| CBC & basic metabolic panel | Annually | Detect inflammatory changes. |
| Review for depression or anxiety | Every visit | Early detection of mood changes. |
Clinical Pearls
- Combining Statins & Evolocumab: When both are used, the LDL‑C reduction is additive. Clinicians may down‑titrate statins if LDL‑C targets are met, potentially reducing statin‑related side effects.
- Weight‑based dosing: Preferred in children or patients >120 kg, ensuring sufficient systemic exposure while minimizing cost.
- Storage: Refrigerate at 2–8 °C; do not freeze. Reconstitute with 0.3 mL of sterile, non‑buffered saline before injection.
- Injection site rotation: To reduce local reactions; use thigh or abdomen alternating.
- Patient education: Emphasize that evolocumab is a *monoclonal antibody*, not a small‑molecule drug; it does not interfere with CYP450 or drug‑drug interactions typical of statins.
- Insurance & cost: Same‑as‑earlier: many payers require statin failure before approving; document LDL‑C target unmet documents ahead of request.
- Post‑marketing surveillance: Monitor reports of new autoimmune phenomena; remain vigilant in patients with prior rheumatologic disorders.
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