lecanemab

General

Genetic Implications:

Pronunciation:
lek-an-e-mab

Trade Name(s)

• Leqembi
• Leqembi IQLIK

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, 53% absorbed following SUBQ administration.

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)

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity.

Use Cautiously in:

•  Black Box:  Apolipoprotein E ε 4 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

Local: injection-related reactions (subq)

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

Calculate IV dose based on actual body weight.

IV SUBQ (Adults): Initial dosing regimen: 10 mg/kg IV every 2 wk for 18 mo. After 18 mo, may optionally continue the initial dosing regimen (10 mg/kg IV every 2 wk) or switch to a maintenance dosing regimen (IV or SUBQ).  IV maintenance dosing regimen: 10 mg/kg IV every 4 wk; administer 1st IV maintenance dose 2 wk after the last dose of the initial dosing regimen. .  SUBQ maintenance dosing regimen: 360 mg SUBQ once weekly; administer 1st SUBQ maintenance dose 2 wk after last IV dose.

Availability

Solution for IV injection: 100 mg/mL

Solution for SUBQ injection: 360 mg/1.8 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: If asymptomatic and mild severity on MRI,  continue therapy.  If asymptomatic and moderate or severe severity on MRI,  hold lecanemab until MRI demonstrates resolution; therapy may then be resumed based on clinical judgment.  If symptoms are mild (discomfort noticed, but no disruption of normal daily activity) with mild severity on MRI,  may continue therapy based on clinical judgment.  If symptoms are mild with moderate or severe severity on MRI,  hold lecanemab until MRI demonstrates resolution and symptoms resolve; therapy may then be resumed based on clinical judgment.  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) regardless of severity on MRI,  hold lecanemab until MRI demonstrates resolution and symptoms resolve; therapy may then be resumed based on clinical judgment.
  • For patients with ARIA-H: If asymptomatic and mild severity on MRI,  continue therapy.  If asymptomatic and moderate or severe severity on MRI,  hold lecanemab until MRI demonstrates resolution and symptoms resolve; use clinical judgment in considering whether to continue or permanently discontinue therapy.  If symptomatic regardless of severity on MRI,  hold lecanemab until MRI demonstrates resolution 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/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.  If infusion-related reaction occurs, ↓infusion rate or discontinue infusion and initiate appropriate therapy. Consider premedication at subsequent dosing with antihistamines, NSAIDs, or corticosteroids.
• Monitor for hypersensitivity reactions (angioedema, bronchospasm, anaphylaxis).  If reaction occurs,  discontinue infusion and initiate appropriate therapy (epinephrine) as indicated.
• Assess for injection site reactions (erythema, induration, swelling, ↑ warmth, rash, pain, itching, redness, hematoma).

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 1 wk before the 3rd, 5th, 7th, and 14th infusions.
• Switching Between Maintenance Dosage Regimens: During maintenance therapy, may switch between IV and SUBQ route of administration. Start new route 1 wk after the last maintenance dose, then continue following regular dosing schedule for the new route.
• SUBQ Remove syringe from refrigerator and allow to reach room temperature for 20 min before use. Solution should be clear to opalescent, colorless to pale yellow, and free of visible particles. Do not use if solution is cloudy or contains particles. Administer into the abdomen, upper thigh, or back of the upper arm. Avoid injecting into moles, scars, bruises, tattoos, or areas where the skin is red, hard, tender, or damaged.

Patient/Family Teaching

• Explain purpose and side effects of medication. Advise patient to read  Patient Information  before starting therapy. If IV initial or maintenance dose is missed, administer next dose as soon as possible. If SUBQ maintenance dose is missed, administer as soon as possible up to 6 days after the missed dose and administer the next dose on the regularly scheduled day. Thereafter, resume the original dosing schedule.
• 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.
•  Inform patient of ↑ risk for ARIA if they are ApoE 4 homozygote, and encourage testing for ApoE 4 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 signs/symptoms of serious or severe hypersensitivity reactions.
• Advise patient that symptoms of infusion-related reactions can occur during or after the infusion and to notify health care provider if reactions occur.
• Advise patient of signs/symptoms of injection-related reactions and to notify health care provider if any occur.
• Providers should encourage patients to participate in real world data collection (e.g., registries) to help further the understanding of Alzheimer disease and the impact of Alzheimer disease treatments. Providers and patients can contact Eisai at 888-274-2378 for a list of currently enrolling programs.
• 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.