lecanemab

General

Genetic Implications: Genetic Implications

Pronunciation:
lek-an-e-mab

Trade Name(s)

  • Leqembi

Ther. Class.

anti-Alzheimers's agents

Pharm. Class.

monoclonal antibodies

anti amyloid monoclonal antibodies

Indications

Alzheimer disease (with mild cognitive impairment or mild dementia).

Action

Acts as a monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta.

Therapeutic Effect(s):

  • Reduction in clinical decline.
  • Reduction in amyloid beta plaques in the brain.

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.

Distribution: Not widely distributed to extravascular tissues.

Metabolism and Excretion: Degraded into small peptides and amino acids via catabolic pathways.

Half-life: 5–7 days.

TIME/ACTION PROFILE (plasma concentrations)

ROUTEONSETPEAKDURATION
IVrapidunknown2 wk

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity.

Use Cautiously in:

  • Genetic implication  Black Box:  Apolipoprotein E ε4 homozygotes (15% of patients with Alzheimer disease) (↑ risk of amyloid-related imaging abnormalities);
  • OB:   Safety not established in pregnancy;
  • Lactation:  Safety not established in breastfeeding;
  • Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: atrial fibrillation

GI: diarrhea

Hemat: lymphopenia

Neuro: AMYLOID-RELATED IMAGING ABNORMALITIES (ARIA) (including edema and hemosiderin deposition), headache, INTRACRANIAL HEMORRHAGE, SEIZURES

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema), infusion-related reactions

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

 Anticoagulant drugs  and  thrombolytics  may ↑ risk of intracerebral hemorrhage.

Route/Dosage

IV (Adults): 10 mg/kg every 2 wk. After 18 mo, may continue with 10 mg/kg every 2 wk or transition to maintenance regimen of 10 mg/kg every 4 wk.

Availability

Solution for injection: 100 mg/mL

Assessment

  • Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the 1st 14 wk of therapy.
    • May cause amyloid related imaging abnormalities edema (ARIA-E) and hemosiderin deposition (ARIA-H). For patients with ARIA-E severity on MRI:  If asymptomatic and mild severity,  continue dosing.  If asymptomatic and moderate or severe severity,  suspend dosing.  If symptoms are mild (discomfort noticed, but no disruption of normal daily activity) with mild severity,  may continue dosing based on clinical judgment.  If symptoms are mild with moderate or severe severity,  suspend dosing.  If symptoms are moderate (discomfort sufficient to reduce or affect normal daily activity) or severe (incapacitating, with inability to work or to perform normal daily activity),  suspend dosing. Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2–4 mo after initial identification. Use clinical judgement when considering resumption of dosing.
    • For patients with ARIA-H severity on MRI:  If asymptomatic and mild severity,  continue dosing.  If asymptomatic and moderate or severe severity,  suspend dosing.  If symptomatic,  suspend dosing.  For mild or moderate severity,  suspend until MRI demonstrates radiographic stabilization and symptoms resolve; use clinical judgement regarding resumption of dosing; consider a follow-up MRI to assess for stabilization 2–4 mo after initial identification.  For severe ARIA-H severity on MRI,  suspend until MRI demonstrates radiographic stabilization and symptoms resolve; use clinical judgment in considering whether to continue or permanently discontinue therapy.
  • If patient develops an intracerebral hemorrhage >1 cm in diameter during therapy, suspend dosing until MRI demonstrates radiographic stabilization and symptoms resolve. Use clinical judgment in considering whether to continue or permanently discontinue therapy.
  • Monitor for signs or symptoms of infusion-related reactions (fever and flu-like symptoms [chills, generalized aches, feeling shaky, joint pain], nausea, vomiting, hypotension, hypertension, oxygen desaturation) during therapy. The infusion rate may be ↓, or the infusion may be discontinued, and appropriate therapy administered. Consider premedication at subsequent dosing with antihistamines, NSAIDs, or corticosteroids.
  • Monitor for hypersensitivity reactions (angioedema, bronchospasm, anaphylaxis).  If hypersensitivity reaction occurs,  discontinue infusion and initiate appropriate therapy (epinephrine) as indicated.

Lab Test Considerations:

Confirm the presence of amyloid beta pathology before starting therapy.

Implementation

  • Obtain a recent (within 1 yr) brain magnetic resonance imaging (MRI) before starting therapy. Obtain an MRI before the 5th, 7th, and 14th infusions.

IV Administration

  • Intermittent Infusion:   Dilution:  Dilute an appropriate volume of solution from vial in 250 mL of 0.9% NaCl. Solution is clear to opalescent and colorless to pale yellow; do not administer solution that is discolored, cloudy, or contains particulate matter. Gently invert to mix; do not shake. Solution is stable for 4 hr at room temperature or if refrigerated; do not freeze. Allow solution to warm to room temperature before infusing.  Concentration: 100 mg/mL. Rate: Infuse over 1 hr through a terminal low-protein-binding 0.2-micron in-line filter. Flush infusion line to ensure all medication is administered.
  • Y-Site Incompatibility:
    • Do not administer other drugs through same IV line

Patient/Family Teaching

  • Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy. If an infusion is missed, schedule next infusion as soon as possible.
  • Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
  • Genetic implication Inform patient of ↑ risk for ARIA if they are ApoE ε4 homozygote, and encourage testing for ApoE ε4 status prior to therapy initiation. Prior to testing, discuss risk of ARIA across genotypes and implications of genetic testing results.
  • Inform patient that symptoms of ARIA can mimic ischemic stroke and to notify a health care provider immediately of stroke symptoms (sudden weakness or numbness, difficulty speaking or understanding, visual changes, severe headache, dizziness) occur.
  • Advise patient to seek immediate medical attention if they experience any symptoms of serious or severe hypersensitivity reactions.
  • Advise patients that the Alzheimer's Network for Treatment and Diagnostics (ALZ-NET) is a voluntary provider-enrolled patient registry that collects information on treatments for Alzheimer disease, including  Leqembi. Encourage patients to participate in the ALZ-NET registry.
  • Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding.

Evaluation/Desired Outcomes

  • Reduction in clinical decline.
  • Reduction in amyloid beta plaques in the brain.