Posology : מינונים

2         DOSAGE AND ADMINISTRATION
2.1      Patient Selection

Confirm the presence of amyloid beta pathology prior to initiating treatment [see Clinical Pharmacology (9)].

2.2      Dosing Instructions
The recommended dosage of LEQEMBI is 10 mg/kg that must be diluted then administered as an intravenous infusion over approximately one hour, once every two weeks.
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.
Table 1: Dosing Recommendations for Patients with ARIA-E

Clinical Symptom                                           ARIA-E Severity on Severity1                                                       MRI2
Mild                             Moderate             Severe
Asymptomatic                May continue dosing              Suspend dosing3      Suspend dosing3 May continue dosing based                    Suspend dosing3
Mild on clinical judgment
Moderate or Severe Suspend dosing3

1
Clinical Symptom Severity Categories:
Mild: discomfort noticed, but no disruption of normal daily activity.
2
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.

Table 2: Dosing Recommendations for Patients with ARIA-H
Clinical Symptom                         ARIA-H Severity on MRI1
Severity                     Mild                         Moderate                    Severe Asymptomatic                 May continue dosing          Suspend dosing2             Suspend dosing3 

Symptomatic                  Suspend dosing2              Suspend dosing2 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     Dilution Instructions

•   Prior to administration, LEQEMBI must be diluted in 250 mL of 0.9% Sodium Chloride Injection.
•   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.
•   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 (8)]. If not administered immediately, 3
store LEQEMBI refrigerated at 2°C to 8°C for up to 4 hours, or at room temperature up to 30°C for up to 4 hours. Do not freeze.

2.5   Administration Instructions

•   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)].