Leqembi Special Precautions

Controlled access programme and registry: In order to promote the safe and effective use of lecanemab, initiation of treatment in all patients should be through a central registration system implemented as part of a controlled access programme.
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity reactions: Hypersensitivity reactions, including angioedema, bronchospasm, and anaphylaxis, have occurred in patients who were treated with lecanemab which may be serious. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity-type reaction, and initiate appropriate therapy (see Dosage & Administration).
Amyloid beta pathology: The presence of amyloid beta pathology must be confirmed via an appropriate test prior to initiating treatment.
Amyloid Related Imaging Abnormalities (ARIA): ARIA can occur spontaneously in patients with Alzheimer's disease. ARIA-H generally occurs in association with an occurrence of ARIA-E.
ARIA usually occurs early in treatment and is usually 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. In patients who experienced ARIA on placebo or with lecanemab, 1/3 experienced recurrent ARIA. Following an initial event of ARIA, the rate of recurrence on resumption of treatment with lecanemab is very common (see Adverse Reactions). Symptoms associated with ARIA usually resolve over time (see Adverse Reactions).
The risk of ARIA, including symptomatic and serious ARIA, is increased in apolipoprotein E ε4 (ApoE ε4) homozygote carriers (see Adverse Reactions). In addition to ARIA, intracerebral haemorrhages greater than 1 cm in diameter have occurred in patients treated with 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 (see Adverse Reactions).
Monitoring for ARIA: Baseline brain MRI and periodic monitoring with MRI are recommended. Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with lecanemab. If a patient experiences symptoms suggestive of ARIA (see Adverse Reactions), clinical evaluation should be performed, including additional MRI testing (see Dosage & Administration).
Radiographic Findings: The radiographic severity of ARIA associated with lecanemab was classified by the criteria shown in Table 2. (See Table 2.)

Click on icon to see table/diagram/image

For patients with asymptomatic radiographic findings of ARIA-E, enhanced clinical vigilance for symptoms of ARIA is recommended (see Adverse Reactions for symptoms). Obtain additional MRIs after 1 to 2 months to assess for resolution, or sooner if symptoms present.
ApoE ε4 Carrier Status and Risk of ARIA: Patients treated with lecanemab who are ApoE ε4 homozygote carriers have a higher incidence of ARIA, including symptomatic serious and recurrent ARIA, compared to heterozygote carriers and non-carriers (see Adverse Reactions). Lecanemab is not indicated for use in patients who are homozygotes (see Indications/Uses).
Increased Intracerebral Haemorrhage Risk: Caution should be exercised when considering the use of lecanemab in patients with factors that indicate an increased risk for intracerebral haemorrhage.
Intracerebral haemorrhages greater than 1 cm in diameter including fatal events have been observed in patients taking both lecanemab and anticoagulants or in patients receiving thrombolytic agents during lecanemab treatment. Additional caution should be exercised when considering the administration of anticoagulants to a patient already being treated with lecanemab.
Concomitant Antithrombotic Medication: Baseline use of antithrombotic medicinal products (aspirin, other antiplatelets, or anticoagulants) was allowed in clinical trials if the patient was on a stable dose. The majority of exposures to antithrombotic medications were to aspirin. An increased risk of ARIA or intracerebral haemorrhage was not observed with antiplatelet use.
Because intracerebral haemorrhages have been observed in patients taking both lecanemab and anticoagulants (see Adverse Reactions), and in patients receiving thrombolytic agents during lecanemab treatment, additional caution should be exercised when considering the administration of anticoagulants or a thrombolytic agent (e.g. tissue plasminogen activator) to a patient already being treated with lecanemab: If anticoagulation needs to be commenced during therapy with lecanemab (for example incident arterial thromboses, acute pulmonary embolism or other life threatening indications) then lecanemab should be paused. Lecanemab can be reinstated if anticoagulation is no longer medically indicated. The use of concomitant aspirin and other antiplatelet therapy is permitted.
There was only limited exposure to thrombolytic agents in the clinical trials however the risk of severe intracranial bleed resulting from concomitant use is plausible. Use of thrombolytic agents should be avoided except for immediately life-threatening indications with no alternative management (e.g., pulmonary embolism with haemodynamic compromise) when the benefits could outweigh the risks.
Because ARIA-E can cause focal neurologic deficits that can mimic an ischemic stroke, treating clinicians should consider whether such symptoms could be due to ARIA-E before giving thrombolytic therapy to a patient being treated with lecanemab.
Treatment with lecanemab should not be initiated in patients receiving ongoing anticoagulant therapy (see Contraindications).
Other Risk Factors for Intracerebral Haemorrhage: Patients were excluded from enrolment in Study 301 for findings on neuroimaging that indicated an increased risk for intracerebral haemorrhage. These included findings suggestive of CAA (prior cerebral haemorrhage greater than 1 cm in greatest diameter, more than 4 microhaemorrhages, superficial siderosis, vasogenic oedema) or other lesions (aneurysm, vascular malformation) that could potentially increase the risk of intracerebral haemorrhage.
The presence of an ApoE ε4 allele is associated with CAA, which has an increased risk for intracerebral haemorrhage.
Infusion related reactions: Infusion related reactions were observed in clinical trials with lecanemab (see Adverse Reactions); the majority were mild or moderate and occurred with the first infusion. In the event of an infusion-related reaction, the infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy initiated as clinically indicated. Prophylactic treatment with antihistamines, acetaminophen, nonsteroidal anti-inflammatory drugs, or corticosteroids prior to future infusions may be considered.
Patients excluded from clinical trials (see also Pharmacology: Pharmacodynamics under Actions): Patients with a history of transient ischemic attacks (TIA), stroke or seizures within 12 months of screening were excluded in the clinical trials with lecanemab. The safety and efficacy in these patients are unknown.
Patients with immunologic disorders who were not adequately controlled or required therapy with immunoglobulins, systemic monoclonal antibodies, systemic immunosuppressants or plasmapheresis were excluded in the clinical trials with lecanemab, hence the safety and efficacy in these patients are unknown.
Patients with autosomal dominant Alzheimer's disease or with Down syndrome may be associated with a higher rate of CAA and ARIA events and have been excluded from clinical trials with lecanemab. The safety and efficacy of lecanemab in these patients are unknown.
Patient card and patient information leaflet: The prescriber must discuss the risks of lecanemab therapy, MRI scans and signs or symptoms of adverse reactions and when to seek attention from a healthcare professional with the patient. The patient will be provided with the patient card and instructed to carry the card at all times.
Excipients with known effect: Dilution with sodium chloride (0.9% saline) is necessary before administration. See the product information for the sodium chloride diluent for information.
This medicine contains 0.5 mg of polysorbate 80 in each 1 mL of lecanemab. Polysorbates may cause allergic reactions. Patients with known allergies shall be taken into consideration.
Effects on ability to drive and use machines: Lecanemab has no or negligible influence on the ability to drive and use machines. Patients should be advised to use caution when driving or operating machinery in case they experience dizziness or confusion during treatment with lecanemab.