Leqembi

2.1        Patient Selection

Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology ( 12.1)].

2.2        Dosing Instructions

The recommended initial dosing regimen of LEQEMBI is 10 mg/kg once every 2 weeks administered as an intravenous infusion over approximately one hour. After 18 months, the regimen of 10 mg/kg once every two weeks may be continued, or a transition to the maintenance dosing regimen of 10 mg/kg once every 4 weeks may be considered [see Clinical Pharmacology ( 12.2)].

LEQEMBI must be diluted before administration [see Dosage and Administration ( 2.4)].

If an infusion is missed, administer the next dose as soon as possible.

2.3        Monitoring and Dosing Interruption for Amyloid Related Imaging Abnormalities

LEQEMBI can cause amyloid related imaging abnormalities -edema (ARIA-E) and -hemosiderin deposition (ARIA-H) [see Warnings and Precautions ( 5.1)].

Monitoring for ARIA

Obtain a recent baseline brain magnetic resonance imaging (MRI) prior to initiating treatment with LEQEMBI. Obtain an MRI prior to the 5th, 7th, and 14th infusions. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including an MRI if indicated.

Recommendations for Dosing Interruptions in Patients with ARIA

ARIA-E

The recommendations for dosing interruptions for patients with ARIA-E are provided in Table 1.

1        Clinical Symptom Severity Categories:
Mild: discomfort noticed, but no disruption of normal daily activity.
Moderate: discomfort sufficient to reduce or affect normal daily activity.
Severe: incapacitating, with inability to work or to perform normal daily activity.
2        See Table 3 for MRI radiographic severity [Warnings and Precautions ( 5.1)].
3        Suspend until MRI demonstrates radiographic resolution and symptoms, if present, resolve; consider a follow-up MRI to assess for resolution 2 to 4 months after initial identification. Resumption of dosing should be guided by clinical judgment.

ARIA-H

The recommendations for dosing interruptions for patients with ARIA-H are provided in Table 2.

1 See Table 3 for MRI radiographic severity [Warnings and Precautions ( 5.1)].

2 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; resumption of dosing should be guided by clinical judgment; consider a follow-up MRI to assess for stabilization 2 to 4 months after initial identification.

3 Suspend until MRI demonstrates radiographic stabilization and symptoms, if present, resolve; use clinical judgment in considering whether to continue treatment or permanently discontinue LEQEMBI.

In patients who develop intracerebral hemorrhage greater than 1 cm in diameter during treatment with LEQEMBI, suspend dosing until MRI demonstrates radiographic stabilization and symptoms, if present, resolve. Use clinical judgment in considering whether to continue treatment after radiographic stabilization and resolution of symptoms or permanently discontinue LEQEMBI.

2.4        Preparation and Administration of LEQEMBI for Intravenous Infusion

Dilution

• Prior to administration, LEQEMBI must be diluted in 250 mL of 0.9% Sodium Chloride Injection, USP.
  
• Use aseptic technique when preparing the LEQEMBI diluted solution for intravenous infusion.
  
• Calculate the dose (mg), the total volume (mL) of LEQEMBI 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 LEQEMBI concentration of 100 mg/mL.
  
• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Check that the LEQEMBI solution is clear to opalescent and colorless to pale yellow. Do not use if opaque particles, discoloration, or other foreign particles are present.
  
• Remove the flip-off cap from the vial. Insert the sterile syringe needle into the vial through the center of the rubber stopper.
  
• Withdraw the required volume of LEQEMBI from the vial(s) and add to an infusion bag containing 250 mL of 0.9% Sodium Chloride Injection, USP.
  
• Each vial is for one-time use only. Discard any unused portion.
  
• Gently invert the infusion bag containing the LEQEMBI diluted solution to mix completely. Do not shake.
  
• After dilution, immediate use is recommended [see Description ( 11)]. If not administered immediately, store LEQEMBI refrigerated at 2°C to 8°C (36°F to 46°F) for up to 4 hours, or at room temperature up to 30°C (86°F) for up to 4 hours. Do not freeze.

Administration

• Visually inspect the LEQEMBI diluted solution for particles or discoloration prior to administration. Do not use if it is discolored, opaque, or foreign particles are seen.
  
• Prior to infusion, allow the LEQEMBI diluted solution to warm to room temperature.
  
• Infuse the entire volume of the LEQEMBI diluted solution intravenously over approximately one hour through an intravenous line containing a terminal low-protein binding 0.2 micron in-line filter. Flush infusion line to ensure all LEQEMBI is administered.
  
• Monitor for any signs or symptoms of an infusion-related reaction. The infusion rate may be reduced, or the infusion may be discontinued, and appropriate therapy administered as clinically indicated. Consider pre-medication at subsequent dosing with antihistamines, non-steroidal anti-inflammatory drugs, or corticosteroids [see Warnings and Precautions ( 5.3)].

8.1        Pregnancy

Risk Summary

There are no adequate data on LEQEMBI use in pregnant women 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 LEQEMBI. 

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.

8.2        Lactation

Risk Summary

There are no data on the presence of lecanemab-irmb 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 breastfeeding should be considered along with the mother’s clinical need for LEQEMBI and any potential adverse effects on the breastfed infant from LEQEMBI or from the underlying maternal condition.

8.4        Pediatric Use

Safety and effectiveness of LEQEMBI in pediatric patients have not been established.

8.5        Geriatric Use

In Studies 1 and 2, the age of patients exposed to LEQEMBI 10 mg/kg every two weeks (n=1059) ranged from 50 to 90 years, with a mean age of 72 years; 81% were 65 years and older, and 39% were 75 years and older. No overall differences in safety or effectiveness of LEQEMBI have been observed between patients 65 years of age and older and younger adult patients.