LEQEMBI® (lecanemab-irmb) injection
Drug UPDATES: [Drug information (pdf)]
PACKAGE INSERT -Dosing: Click (+) next to Dosage and Administration section (drug info link)
Vial: 100 mg/mL
Must use a terminal low-protein binding 0.2 micron in-line filter
If an infusion is missed, administer the next dose as soon as possible.
- 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.
- 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.
- 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.
| WARNING: WARNING: AMYLOID RELATED IMAGING ABNORMALITIES Monoclonal antibodies directed against aggregated forms of beta amyloid, including LEQEMBI, 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 [see WARNINGS AND PRECAUTIONS (5.1), ADVERSE REACTIONS (6.1)]. ApoE ε4 Homozygotes Patients who are apolipoprotein E ε4 (ApoE ε4) homozygotes (approximately 15% of Alzheimer’s disease patients) treated with this class of medications, including LEQEMBI, 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 LEQEMBI; however, it cannot be determined if they are ApoE ε4 homozygotes and at higher risk for ARIA [see WARNINGS AND PRECAUTIONS (5.1)]. Consider the benefit of LEQEMBI for the treatment of Alzheimer’s disease and potential risk of serious adverse events associated with ARIA when deciding to initiate treatment with LEQEMBI [see WARNINGS AND PRECAUTIONS (5.1) and CLINICAL STUDIES (14)].Drug information (pdf) |
Lecanemab-irmb is a recombinant humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta, and is expressed in a Chinese hamster ovary cell line. Lecanemab-irmb has an approximate molecular weight of 150 kDa.
LEQEMBI (lecanemab-irmb) injection is a preservative-free, sterile, clear to opalescent and colorless to pale yellow solution for intravenous use by infusion after dilution. LEQEMBI is supplied in single-dose vials available in concentrations of 500 mg/5 mL (100 mg/mL) or 200 mg/2 mL (100 mg/mL).
Each mL of solution contains 100 mg of lecanemab-irmb and arginine hydrochloride (42.13 mg), histidine (0.18 mg), histidine hydrochloride monohydrate (4.99 mg), polysorbate 80 (0.50 mg), and Water for Injection at an approximate pH of 5.0.
Lecanemab-irmb is a humanized immunoglobulin gamma 1 (IgG1) monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. The accumulation of amyloid beta plaques in the brain is a defining pathophysiological feature of Alzheimer’s disease. LEQEMBI reduces amyloid beta plaques, as evaluated in Study 1 and Study 2.
LEQEMBI is indicated for the treatment of Alzheimer’s disease. Treatment with LEQEMBI should be initiated in patients with mild cognitive impairment or mild dementia stage of disease, the population in which treatment was initiated in clinical trials.
LEQEMBI is contraindicated in patients with serious hypersensitivity to lecanemab-irmb or to any of the excipients of LEQEMBI.
- Amyloid Related Imaging Abnormalities (ARIA): Enhanced clinical vigilance for ARIA is recommended during the first 14 weeks of treatment with LEQEMBI. Risk of ARIA, including symptomatic ARIA, was increased in apolipoprotein E ε4 homozygotes compared to heterozygotes and noncarriers. If a patient experiences symptoms suggestive of ARIA, clinical evaluation should be performed, including MRI scanning if indicated. (2.3, 5.1) Drug information (pdf)
- Infusion-Related Reactions: 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. (5.3)
Most common adverse reactions (at approximately 10% and higher incidence compared to placebo): infusion-related reactions, amyloid related imaging abnormality-microhemorrhages, amyloid related imaging abnormality-edema/effusion, and headache. (6.1)
See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide. Drug information (pdf)
2.1 Patient Selection
Confirm the presence of amyloid beta pathology prior to initiating treatment [see CLINICAL PHARMACOLOGY (12.1)]. Drug information (pdf)
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.
| Clinical Symptom Severity1 | ARIA-E Severity on MRI2 | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing | Suspend dosing3 | Suspend dosing3 |
| Mild | May continue dosing based on clinical judgment | Suspend dosing3 | |
| Moderate or Severe | Suspend dosing3 |
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 severity [WARNINGS AND PRECAUTIONS (5.1)].
Drug information (pdf)
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.
| Clinical Symptom Severity | ARIA-H Severity on MRI1 | ||
| Mild | Moderate | Severe | |
| Asymptomatic | May continue dosing | Suspend dosing2 | Suspend dosing3 |
| Symptomatic | Suspend dosing2 | Suspend dosing2 |
1 See TABLE 3 for MRI severity [Warnings and Precautions (5.1)].
Drug information (pdf)
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.
- 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.
2.5 Administration Instructions
- Visually inspect the LEQEMBI diluted solution for particles or discoloration prior to administration. Do not use if it is discolored, or 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)].
Injection:
- 500 mg/5 mL (100 mg/mL) solution in a single-dose vial
- 200 mg/2 mL (100 mg/mL) solution in a single-dose vial
Unopened Vial
Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
Store in the original carton to protect from light.
Do not freeze or shake.
Diluted Solution
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.
