Leqembi
Leqembi
Generic Name
Leqembi
Mechanism
- Selective binding to soluble Aβ protofibrils, sparing monomeric and fibrillar Aβ.
- Immune‑mediated clearance via microglial Fcγ receptors, enhancing phagocytosis of Aβ deposits.
- Reduction in cerebral amyloid plaque burden → slows clinical decline in mild cognitive impairment and mild AD.
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Pharmacokinetics
| Parameter | Detail |
| Administration | Intravenous infusion (10 mg/kg, 2 h). |
| Half‑life | ~30 days (steady‑state achieved ≈ 4 months). |
| Volume of distribution | 4.6 L (limited to vascular and CNS compartments). |
| Clearance | Linear, 5.4 L/day; no dose adjustment for age, weight, or mild renal/hepatic impairment. |
| Steady‑state | Reached after ~4–5 infusions; maintenance dosing q2 weeks thereafter. |
| Metabolism | Protein catabolism via the reticuloendothelial system; no significant CYP interactions. |
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Indications
- Early Alzheimer’s disease (age ≥ 40 y) presenting as mild cognitive impairment or mild dementia due to AD.
- Confirmed amyloid pathology: positive amyloid PET scan or CSF Aβ₁–₄₀/₁–₄₂ ratio.
- Eligible for risk‑management tools (e.g., Amyloid‑Related Imaging Abnormalities [ARIA] monitoring).
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Contraindications
| Category | Note |
| Contraindications | Severe ARIA risk (history of ARIA‑h in a previous trial), known hypersensitivity to lecanemab components. |
| Warnings |
• Amyloid‑Related Imaging Abnormalities (ARIA) – edema (ARIA‑e) or microhemorrhage/bruising (ARIA‑h). • Hypersensitivity/anaphylaxis during infusion. |
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Dosing
- Initial dose: 10 mg/kg IV infusion over 2 h, every 2 weeks.
- Concentration: 10 mg/mL in sterile infusion solution.
- Premedication: Antihistamine (e.g., diphenhydramine 25 mg) *optional* for patients with prior infusion reactions.
- Monitoring: Vital signs pre‑, during, and post‑infusion; watch for chills, fever, rash.
- Duration: Continuous infusion for at least 3–5 years or until disease progression.
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Adverse Effects
- Common
- Infusion‑related reactions (fever, chills, rash, headache).
- Headache, dizziness, fatigue, back pain.
- Mild elevated liver enzymes (rare).
- Serious
- Amyloid‑Related Imaging Abnormalities (ARIA‑e or ARIA‑h).
- Severe hypersensitivity/anaphylaxis.
- Opportunistic infections (no increased infection rate reported).
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Monitoring
| Parameter | Frequency | Rationale |
| MRI (baseline + 6‑month intervals) | Pre‑treatment, 3 months after first 4 infusions, then every 6 months | Detect ARIA before clinical symptoms. |
| Vital signs during infusion | Every 15 min during infusion | Identify infusion reactions early. |
| Cognitive testing (MMSE or MoCA) | Every 6 months | Track disease progression. |
| Blood chemistry (CBC, CMP) | Every 3 months | Monitor for liver dysfunction or cytopenia. |
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Clinical Pearls
- Baseline MRI is essential: Any asymptomatic ARIA‑h identified pre‑treatment increases risk; patients with ≥ 3 microhemorrhages should be excluded.
- ARIA risk stratification: The presence of APOE ε4 allele (especially 2 copies) increases ARIA‑e risk 3‑fold; consider genotype testing when baseline MRI is ambiguous.
- Management of ARIA:
- ARIA‑e > 5 mm: Pause treatment, repeat MRI in 4 weeks.
- ARIA‑h: Manage as with any cerebral microbleed; if symptomatic or > 10 mm, hold treatment indefinitely.
- Patient education: Inform patients to report sudden headache, visual changes, or neurological deficits promptly; early recognition reduces adverse outcomes.
- Infusion monitoring: Even with antiallergic premedication, always keep antivenom ready; most reactions occur within the first 30 min.
- Drug–drug interactions: None clinically significant, but avoid concomitant IVIG or rituximab within 4 weeks to reduce potential for cross‑reactivity.
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• Leqembi represents a paradigm shift in AD therapy, targeting amyloid pathology while demanding careful monitoring for ARIA. Its use continues to be refined through post‑marketing registries, offering critical real‑world insights into efficacy, safety, and optimal patient selection.