Version May 2024
Monoclonal antibodies directed against aggregated forms of beta amyloid, including lecanemab, can cause amyloid-related imaging abnormalities (ARIA), characterized as ARIA with edema (ARIA-E) and ARIA with hemosiderin deposition (ARIA-H). Incidence and timing of ARIA vary among treatments. ARIA usually occurs early in treatment and is usually asymptomatic, although serious and life-threatening events rarely can occur. Serious intracerebral hemorrhages, some of which have been fatal, have been observed in patients treated with this class of medications.
ApoE ε4 homozygotes: Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer disease patients) treated with this class of medications, including lecanemab, have a higher incidence of ARIA, including symptomatic, serious, and severe radiographic ARIA, compared to heterozygotes and noncarriers. Testing for ApoE ε4 status should be performed prior to initiation of treatment to inform the risk of developing ARIA. Prior to testing, prescribers should discuss with patients the risk of ARIA across genotypes and the implications of genetic testing results. 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 ApoE ε4 homozygotes and at higher risk for ARIA.
Consider the benefit of lecanemab for the treatment of Alzheimer disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with lecanemab.
Note: Confirm the presence of amyloid beta pathology prior to treatment initiation. Testing for apolipoprotein E ε4 (ApoE ε4) status prior to treatment initiation is recommended.
Alzheimer disease: IV: Dosing based on actual body weight: 10 mg/kg once every 2 weeks.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; however, lecanemab is not expected to undergo renal elimination.
There are no dosage adjustments provided in the manufacturer's labeling; however, lecanemab is not expected to undergo hepatic metabolism.
Amyloid-related imaging abnormalities (ARIA), symptoms: Perform clinical evaluation, including MRI if indicated.
Amyloid-related imaging abnormalities – edema (ARIA-E): See table below:
|
Severity of clinical symptomsa |
ARIA-E severity on MRI | |
|---|---|---|
|
Mild |
Moderate or severe | |
|
a For patients experiencing symptoms associated with ARIA, perform clinical evaluation, including MRI if indicated. | ||
|
Asymptomatic |
Continue current lecanemab dosing. |
Withhold lecanemab until MRI shows radiographic resolution. Consider follow-up MRI to assess for resolution (eg, 2 to 4 months following initial ARIA-E identification); resume dosing based on clinical judgment. |
|
Milda (eg, discomfort but no disruption of normal daily activity) |
Continue lecanemab dosing based on clinical judgment. |
Withhold lecanemab until MRI shows radiographic resolution and symptoms resolve. Consider follow-up MRI to assess for resolution (eg, 2 to 4 months following initial ARIA-E identification); resume dosing based on clinical judgment. |
|
Moderate or severea (eg, symptoms ranging from discomfort that impacts normal daily activity to incapacitation and inability to perform normal daily activity or work) |
Withhold lecanemab until MRI shows radiographic resolution and symptoms resolve. Consider follow up MRI to assess for resolution (eg, 2 to 4 months following initial ARIA-E identification); resume dosing based on clinical judgment. | |
Amyloid-related imaging abnormalities – hemosiderin (ARIA-H): See table below:
|
Severity of clinical symptomsa |
ARIA-H Severity on MRI | ||
|---|---|---|---|
|
Mild |
Moderate |
Severe | |
|
a For patients experiencing symptoms associated with ARIA, perform clinical evaluation, including MRI if indicated. | |||
|
Asymptomatic |
Continue current lecanemab dosing. |
Withhold lecanemab until MRI shows radiographic stabilization. Consider follow up MRI to assess for resolution (eg, 2 to 4 months following initial ARIA-H identification); resume dosing based on clinical judgment. |
Withhold lecanemab until MRI shows radiographic stabilization. Use clinical judgment to determine whether to continue treatment or permanently discontinue lecanemab. |
|
Symptomatica |
Withhold lecanemab until MRI shows radiographic stabilization and symptoms resolve. Consider follow up MRI to assess for resolution (eg, 2 to 4 months following initial ARIA-H identification); resume dosing based on clinical judgment. |
Withhold lecanemab until MRI shows radiographic stabilization and symptoms resolve. Use clinical judgment to determine whether to continue treatment or permanently discontinue lecanemab. | |
Intracerebral hemorrhage >1 cm in diameter: Withhold lecanemab until MRI shows radiographic stabilization and symptoms (if present) resolve. Use clinical judgment to determine whether to continue treatment or permanently discontinue lecanemab.
Hypersensitivity reaction signs/symptoms (eg, angioedema, bronchospasm, anaphylaxis ): Promptly discontinue infusion at first sign/symptom of hypersensitivity and initiate appropriate treatment.
Infusion reaction signs/symptoms (eg, fever, flu-like symptoms, nausea, vomiting, BP changes): Consider reducing rate of administration, discontinuing the infusion, and/or initiating supportive therapy as clinically appropriate. Consider premedication with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions.
Refer to adult dosing.
Amyloid-related imaging abnormalities (ARIA), including ARIA consistent with vasogenic edema and/or sulcal effusions (ARIA-E) (Ref) and ARIA with hemosiderin deposition (ARIA-H) characterized by superficial siderosis, microhemorrhages, and macrohemorrhages (Ref) have been reported with lecanemab therapy. Patients may develop ARIA-H with concomitant ARIA-E. In patients who developed ARIA during lecanemab clinical trials, most cases were asymptomatic with mild to moderate radiographic severity; however, serious and/or fatal symptoms have been reported (Ref). Recurrent episodes of ARIA-E have also been described (Ref). Clinical symptoms suggesting ARIA may include abnormal gait, confusion, dizziness, focal neurologic deficits, headache, nausea, visual disturbance, and seizures. Resolution of ARIA (-E and/or -H) occurred within 4 months in the majority of cases in clinical trials (Ref).
Mechanism: Not clearly established; speculated that increased clearance of amyloid from parenchymal plaques into perivascular space may result in excess fluid shifts. This movement of amyloid into cerebral vessel walls may also increase vascular friability and permeability, thus impairing vessel wall integrity to permit small amounts of blood passage. Increased vascular permeability at which both fluid and red blood cells cross the vessel wall may suggest a common pathophysiologic mechanism for both ARIA-E and ARIA-H (Ref).
ARIA-E: Dose-related; related to the pharmacologic action. Increased cerebrovascular permeability due to antibody binding to deposited amyloid-beta results in an increase in extracellular fluid volume and vasogenic edema (Ref).
ARIA-H: Dose-related; related to the pharmacologic action. Leakage of blood from a vessel into adjacent tissue parenchyma or subarachnoid space/periadventitial compartments leaves residual deposits of iron in the form of hemosiderin, resulting in superficial siderosis and/or radiographic evidence of hemorrhage (Ref).
Onset: Varied; ARIA may occur at any time during treatment, but most events occur within the first 3 months (Ref).
Risk factors:
ARIA-E:
• Apolipoprotein E ε4 carriers; specifically ApoE ε4 homozygotes
• Dose; risk increases with higher doses (Ref)
ARIA-H: Microhemorrhages:
• Apolipoprotein E ε4 carriers; specifically ApoE ε4 homozygotes
• Increasing age (Ref)
• Older adults with cardiovascular risk factors and/or evidence of prior cerebrovascular event (Ref)
• Concomitant risk factors for intracerebral hemorrhages (prior cerebral hemorrhage >1 cm, >4 microhemorrhages, superficial siderosis, vasogenic edema, aneurysm, vascular malformation)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.
>10%:
Hematologic & oncologic: Hemosiderosis (ARIA-H, including microhemorrhage and superficial siderosis: 6% to 17%)
Hypersensitivity: Infusion-related reaction (20% to 26%)
Nervous system: Brain edema (ARIA-E, including sulcal effusion: 10% to 13%), headache (11% to 14%) (table 1)
|
Drug (Lecanemab) |
Placebo |
Dose |
Number of Patients (Lecanemab) |
Number of Patients (Placebo) |
|---|---|---|---|---|
|
14% |
10% |
10 mg/kg every 2 weeks |
161 |
245 |
|
11% |
8% |
10 mg/kg every 2 weeks |
898 |
897 |
1% to 10%:
Cardiovascular: Atrial fibrillation (3%)
Dermatologic: Skin rash (6%)
Gastrointestinal: Diarrhea (8%), nausea and vomiting (6%)
Hematologic & oncologic: Lymphocytopenia (4%)
Respiratory: Cough (9%)
<1%: Nervous system: Cerebral hemorrhage
Frequency not defined:
Hematologic & oncologic: Increased neutrophils
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis and angioedema)
Serious hypersensitivity (eg, anaphylaxis, angioedema) to lecanemab or any component of the formulation.
Concerns related to adverse effects:
• Infusion reaction: Lecanemab may cause infusion reactions; symptoms include fever, flu-like symptoms (chills, generalized aches, shakiness, joint pain), nausea, vomiting, hypotension, hypertension, and oxygen desaturation. The highest incidence of infusion reactions occurs with the first infusion.
Dosage form specific issues:
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Leqembi: Lecanemab-irmb 200 mg/2 mL (2 mL); Lecanemab-irmb 500 mg/5 mL (5 mL) [contains polysorbate 80]
No
Solution (Leqembi Intravenous)
200 mg/2 mL (per mL): $152.89
500 mg/5 mL (per mL): $152.88
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
IV: Dilution required prior to administration. Administer by IV infusion over 1 hour through an IV line containing a terminal low-protein binding 0.2 micron in-line filter. Flush IV line following infusion.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Leqembi: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761269s001lbl.pdf#page=21
Alzheimer disease: Treatment of Alzheimer disease; to be initiated in patients with mild cognitive impairment or mild dementia stage of disease.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Lecanemab may enhance the adverse/toxic effect of Agents with Antiplatelet Properties. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Anticoagulants: Lecanemab may enhance the adverse/toxic effect of Anticoagulants. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy
Thrombolytic Agents: Lecanemab may enhance the adverse/toxic effect of Thrombolytic Agents. Specifically, the risk of hemorrhage may be increased. Risk C: Monitor therapy
Animal reproduction studies have not been conducted.
Lecanemab is a humanized monoclonal antibody (IgG1). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).
It is not known if lecanemab is present in breast milk.
Lecanemab is a humanized monoclonal antibody (IgG1). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
PET or lumbar puncture to confirm presence of amyloid beta pathology (prior to initiation) (van Dyck 2023); apolipoprotein E ε4 (ApoE ε4) status testing (prior to initiation); brain MRI (prior to initiation [within 1 year]; prior to 5th, 7th, 14th infusions; periodically as appropriate in the setting of amyloid-related imaging abnormalities (ARIA) [eg, 2 to 4 months following identification of ARIA]); monitor closely for clinical and MRI changes; monitor for symptoms suggestive of ARIA (eg, headache, altered mental status, visual changes, dizziness, nausea, gait difficulty, focal neurologic deficits, seizure).
Lecanemab is a humanized monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. Lecanemab reduces amyloid beta plaques, the accumulation of which is a defining pathophysiological feature of Alzheimer disease.
Distribution: Vdss: 3.24 L.
Metabolism: Degradation by proteolytic enzymes.
Half-life elimination: 5 to 7 days.
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