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lecanemab
Classes
Anti-Alzheimer Agents, Monoclonal Antibodies that Target Amyloid Beta
Administration
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Prior to dilution, the injection is a clear to opalescent and colorless to pale yellow solution. Do not use if opaque particles, discoloration, or foreign particles are present.
Missed dose: If an infusion is missed, administer the missed dose as soon as possible.
Preparation of IV infusion
Use aseptic technique when preparing. The injection solution must be further diluted as an infusion prior to administration.
Each vial is for single-use only and is preservative-free. Discard any unused portion.
Calculate the dose and total volume of lecanemab solution required, and the number of vials needed based on the patient's actual body weight and the recommended dose of 10 mg/kg. Each vial contains a lecanemab concentration of 100 mg/mL; more than 1 vial may be needed for a full dose. Select the correct number of vial(s) for the required dose.
Withdraw the required volume of lecanemab from the vial(s) and add to an infusion bag of 250 mL of 0.9% Sodium Chloride Injection. Do not use any other intravenous diluents to prepare the infusion.
Gently invert the infusion bag to mix completely; do not shake.
Storage: After dilution, immediate use is recommended. If not administered immediately, store the prepared infusion in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) for up to 4 hours, or at room temperature up to 30 degrees C (86 degrees F) for up to 4 hours. Do not freeze.
IV infusion Administration
Prior to infusion, allow the prepared IV infusion solution to warm to room temperature. Inspect before administration. Do not use if it is discolored, opaque, or if foreign particles are seen. Do not shake.
Infuse intravenously over approximately 1 hour through an IV line containing a terminal low-protein binding 0.2 micron in-line filter.
Flush infusion line to ensure all lecanemab is administered.
Monitor for any signs or symptoms of an infusion-related reaction. Infusion rate may be reduced or infusion may be interrupted or discontinued, and appropriate therapy administered as clinically indicated. Consider pre-medication with antihistamines, acetaminophen, non-steroidal anti-inflammatory drugs, or corticosteroids prior to future infusions.
Adverse Reactions
atrial fibrillation / Early / 3.0-3.0
intracranial bleeding / Delayed / Incidence not known
visual impairment / Early / Incidence not known
seizures / Delayed / Incidence not known
cerebral edema / Early / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
infusion-related reactions / Rapid / 20.0-26.0
amyloid-related imaging abnormalities / Delayed / 21.0-21.0
lymphopenia / Delayed / 4.0-4.0
hypertension / Early / Incidence not known
hypotension / Rapid / Incidence not known
confusion / Early / Incidence not known
hemosiderosis / Delayed / Incidence not known
erythema / Early / Incidence not known
headache / Early / 11.0-14.0
cough / Delayed / 9.0-9.0
diarrhea / Early / 8.0-8.0
nausea / Early / 6.0-6.0
vomiting / Early / 6.0-6.0
rash / Early / 6.0-6.0
chills / Rapid / Incidence not known
fever / Early / Incidence not known
dizziness / Early / Incidence not known
gait disturbance / Delayed / Incidence not known
acneiform rash / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
Boxed Warning
Monoclonal antibodies directed against aggregated forms of beta amyloid, including lecanemab, can cause amyloid-related imaging abnormalities (ARIA) and these are addressed in a boxed warning in the product label. These abnormalities may appear as ARIA with edema (ARIA-E), which can be observed on a brain magnetic resonance imaging (MRI) as cerebral edema or sulcal effusions. ARIA with hemosiderin deposition (ARIA-H), which includes microhemorrhage (small areas of intracranial bleeding) and superficial siderosis (hemosiderosis), may also occur. ARIA can occur spontaneously in those with Alzheimer's disease. ARIA-H associated with monoclonal antibodies directed against aggregated forms of beta amyloid generally occurs in association with an occurrence of ARIA-E. ARIA usually occur early in treatment and are often asymptomatic, although serious and life-threatening events, including seizure and status epilepticus, rarely can occur. When present, reported symptoms associated with ARIA may include headache, confusion, visual changes, dizziness, nausea, and gait difficulty. Focal neurologic deficits may also occur. Symptoms associated with ARIA typically resolve over time. In order to determine baseline status and monitor for ARIA, a recent (within 1 year) brain MRI should be obtained before initiating treatment with lecanemab. Perform follow-up MRIs prior to the 5th, 7th, and 14th infusions. Enhanced clinical vigilance for ARIA is particularly recommended during the first 14 weeks of treatment, but monitor treated individuals throughout therapy. If ARIA occur, the severity of symptoms (if present) or severity of ARIA-E or -H may affect decisions to continue or suspend treatment. For patients experiencing moderate or severe symptoms of ARIA-E, moderate or severe severity of ARIA-E, or mild to moderate severity of ARIA-H, suspend treatment until the MRI demonstrates radiographic resolution and symptoms (if present) resolve. Perform an additional follow-up MRI 2 to 4 months following initial identification to assess for resolution of ARIA. Likewise, suspend treatment in those who develop severe ARIA-H as shown on MRI until radiographic stabilization and symptoms (if present) resolve; use clinical judgement to decide to resume treatment or permanently discontinue lecanemab. The risk of experiencing ARIA and related symptoms may also be related to the patient's genetics. In a clinical trial of lecanemab, the incidence of ARIA was higher in patients who were apolipoprotein Eepsilon4 (ApoEepsilon4) homozygotes (45% on lecanemab vs 22% on placebo) than in heterozygotes (19% on lecanemab vs 9% on placebo) and noncarriers (13% on lecanemab vs 4% on placebo). Symptomatic ARIA occurred in 9% of ApoEepsilon4 homozygotes, 2% of heterozygotes, and 1% noncarriers. Serious ARIA events occurred in 3% of homozygotes and approximately 1% of heterozygotes and noncarriers. The recommendations for management of ARIA do not differ between ApoEepsilon4 carriers and noncarriers; however, testing for ApoEepsilon4 should be performed prior to initiation of treatment to educate patients or caregivers of the risk of developing ARIA. Prescribers should inform patients that if genotype testing is not performed they can still be treated with lecanemab; however, it cannot be determined if they are ApoEepsilon4 homozygotes and at higher risk for ARIA. An FDA-authorized test for the detection of ApoEepsilon4 alleles to identify patients at risk for ARIA if treated with lecanemab is not currently available. Currently, available tests used to identify these alleles may vary in accuracy and design. In addition to ARIA, intracerebral hemorrhages greater than 1 cm in diameter have occurred in patients treated with lecanemab. Fatal events of intracerebral hemorrhage have also been observed in patients taking lecanemab. Consider the benefit of lecanemab for the treatment of Alzheimer's disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with lecanemab.
Common Brand Names
LEQEMBI
Dea Class
Rx
Description
Amyloid beta-directed monoclonal antibody given as an IV infusion every 2 weeks
Used for the treatment of adults with Alzheimer's disease with mild cognitive impairment or early dementia stage of AD
Safety issues include serious infusion-related reactions and a warning for amyloid-related imaging abnormalities (ARIA)
Dosage And Indications
Initiate treatment in persons with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials. There are no safety or effectiveness data on initiating treatment at earlier or later stages of the disease than were studied.
10 mg/kg IV infusion every 2 weeks.
Dosing Considerations
No clinical studies were conducted in these patients; however, lecanemab is degraded by proteolytic enzymes and is not expected to undergo hepatic metabolism.
No clinical studies have been conducted in these patients; however, lecanemab is degraded by proteolytic enzymes and not expected to undergo renal elimination.
Drug Interactions
There are no drug interactions associated with Lecanemab products.
How Supplied
LEQEMBI Intravenous Inj Sol: 1mL, 100mg
Maximum Dosage
10 mg/kg IV infusion once every 2 weeks.
10 mg/kg IV infusion once every 2 weeks.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Safety and efficacy have not been established.
Mechanism Of Action
The accumulation of amyloid beta plaques in the brain is a defining pathophysiologic feature of Alzheimer's disease. Lecanemab is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta, reducing amyloid beta plaques over time.
Pharmacokinetics
Lecanemab is administered intravenously. The mean volume of distribution at steady state is 3.24 L (3.18 to 3.30 L). Lecanemab is degraded by proteolytic enzymes in the same manner as endogenous IgG. Lecanemab clearance is 0.370 L/day (0.353 to 0.384 L/day). The terminal half-life is 5 to 7 days.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
Steady-state concentrations of lecanemab were reached after 6 weeks of 10 mg/kg IV infusion dosing every 2 weeks and systemic accumulation was 1.4-fold. The peak concentration (Cmax) and exposure (AUC) of lecanemab increased dose proportionally in the dose range of 0.3 to 15 mg/kg following a single dose.
Pregnancy And Lactation
There are no adequate data on lecanemab use during human pregnancy to evaluate for a drug associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. No animal studies have been conducted to assess the potential reproductive or developmental toxicity of lecanemab.
There are no data on the presence of lecanemab in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Published data from other monoclonal antibodies generally indicate low passage of monoclonal antibodies into human milk and limited systemic exposure in the breastfed infant. The effects of this limited exposure are unknown. The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for lecanemab and any potential adverse effects on the breastfed infant from lecanemab or from the underlying maternal condition.