LEQEMBI 100 mg/mL concentrate for infusion solution

2. What you need to know before you use LEQEMBI

Do not use LEQEMBI

• if you are allergic to lecanemab or any of the other ingredients of this medicine (listed in section 6);
• if you have an uncontrolled bleeding disorder;
• if the magnetic resonance imaging (MRI; a medical imaging technique that uses a magnetic field and computer-generated radio waves to produce detailed images of the body's organs and tissues) scan of the brain shows small spots of bleeding or fluid in the brain or signs of a larger bleed in the past;
• if you are taking medicines to prevent blood clots (called anticoagulants).

Warnings and precautions

Allergic reactions

Tell your doctor immediately if you have an allergic reaction during or immediately after administration of LEQEMBI. See the signs of an allergic reaction in section 4.

Abnormal amyloid-related images (ARIA)

LEQEMBI may cause a side effect called abnormal amyloid-related images or "ARIA". There are two main types of ARIA:

• The buildup of fluid in one or more areas of the brain (this is called ARIA-E).
• Spots of bleeding in the brain, or on the surface of the brain (this is called ARIA-H).

Most people with ARIA do not have symptoms. ARIA symptoms may occur in 2 out of 100 patients. The symptoms include headache, confusion, dizziness, blurred vision, nausea, difficulty walking, or seizures (epileptic). In a small number of people (less than 1 in 100 people), these symptoms can be severe.

Contact your doctor immediately if you experience any of these symptoms.

ARIA is visible on a brain MRI.

Your doctor will schedule MRI scans before the administration of the 5th, 7th, and 14th doses of LEQEMBI. This is a routine safety check to see if you have ARIA. Additional scans may be performed at any time during treatment if your doctor considers it necessary for you.

Your doctor may temporarily or permanently stop treatment with LEQEMBI depending on the results of the MRI.

Genetic risk factors for developing ARIA

Some people carry a gene called "apolipoprotein E4", also known as ApoE4. This means they may have a higher risk of developing ARIA. Your doctor may perform an ApoE4 genetic test to check if you carry the gene and if you have a higher risk of developing ARIA.

Medicines used to prevent or dissolve blood clots

The risk of having a major bleed in the brain (known as intracerebral hemorrhage) with LEQEMBI treatment is higher in patients who are taking medicines used to prevent blood clots (anticoagulants) or to dissolve them (thrombolytics).

Tell your doctor that you are receiving LEQEMBI treatment before receiving any medicine to prevent or dissolve blood clots. LEQEMBI can be used with aspirin and other medicines that prevent blood cells from sticking together (antiplatelet agents).

Infusion-related reactions

Infusion-related reactions are a very common side effect that can be severe (see symptoms in section 4). If you have an infusion-related reaction, you may be given medicines before infusions to reduce the chance of having an infusion-related reaction. These medicines may be antihistamines, paracetamol, anti-inflammatory medicines, and steroids. You will be monitored for 2.5 hours after the first infusion to check for any signs of an infusion-related reaction.

Autosomal dominant Alzheimer's disease and adults with Down syndrome

The use of LEQEMBI for the treatment of autosomal dominant Alzheimer's disease or in adults with Down syndrome has not been established.

Mini-stroke (transient ischemic attack, TIA), stroke, or seizures

Tell your doctor before you are given LEQEMBI if you have had a mini-stroke (transient ischemic attack), stroke, or seizures in the last 12 months. The use of LEQEMBI in patients who have had a mini-stroke, stroke, or seizures has not been established.

Patients with reduced immune response or taking immunosuppressants

Tell your doctor before you are given LEQEMBI if you have an immune system disorder or if you are taking any other medicine by injection or medicines that suppress the immune system. The use of LEQEMBI in patients with a weakened immune system has not been established.

Children and adolescents

LEQEMBI is not indicated for use in children and adolescents under 18 years of age.

Other medicines and LEQEMBI

Tell your doctor if you are taking, have recently taken, or might take any other medicines. In particular, tell your doctor:

• if you are taking medicines to prevent blood clots (called anticoagulants). LEQEMBI must not be used with these medicines.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor for advice before taking this medicine. It is not known if LEQEMBI can harm the fetus.

If you can become pregnant, you must use a contraceptive method during treatment with LEQEMBI and for 2 months after the last dose of LEQEMBI. Before treatment, it must be checked that you are not pregnant.

If you become pregnant while using LEQEMBI, tell your doctor. The use of LEQEMBI is not recommended if you are pregnant.

If you are breastfeeding, you may discuss with your doctor whether to continue breastfeeding or treatment. It is not known if LEQEMBI passes into breast milk.

Driving and using machines

When taking LEQEMBI, some patients may experience symptoms such as dizziness or confusion. This could affect the ability to drive or use machines. If you experience these side effects due to LEQEMBI, ask your doctor if you can continue driving or using machines.

LEQEMBI contains polysorbate 80

This medicine contains 0.5 mg of polysorbate per ml of LEQEMBI. Polysorbates may cause allergic reactions. Tell your doctor if you have any known allergy.

This medicine does not contain sodium, but the concentrate must be diluted with sodium chloride solution, so this must be taken into account for daily sodium intake.

Patient information card

In the patient information card that your doctor has given you, you will also find the key messages of this leaflet. It is important that you always carry this patient information card with you and show it to your partner or caregiver.

3. How to use LEQEMBI

You will be given LEQEMBI under the supervision of a healthcare professional.

Dosage

The recommended dose is 10 milligrams per kilogram of body weight (mg/kg). You should receive it every 2 weeks.

LEQEMBI is given with a "drip" (a needle placed in a vein), also called intravenous infusion (i.v.). Each infusion will take approximately 1 hour.

If you miss an infusion of LEQEMBI

If you miss an infusion of LEQEMBI, talk to your doctor to schedule an infusion as soon as possible. Do not wait until the next scheduled infusion.

When to stop using LEQEMBI

Your doctor may recommend stopping treatment temporarily or permanently, depending on the results of clinical tests, if you develop ARIA or if you experience other side effects.

If you have any other questions about the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

The following side effects have been reported with LEQEMBI:

Serious side effects

Up to 1 in 10 peoplemay experience the following side effect:

• An allergic reaction during or immediately after administration of the medicine. The signs of an allergic reaction are: swelling under the skin, difficulty breathing due to narrowing of the airways, potentially life-threatening severe allergic reaction, rash, and headache.

Up to 1 in 100 peoplemay experience the following side effect:

• Large areas of bleeding in the brain (known as intracerebral hemorrhages). This can cause symptoms such as severe headache, confusion, seizures, or stroke.

Contact your doctor immediately if you experience these side effects.

Other side effects

Up to 1 in 10 peoplemay experience the following side effects:

• Infusion-related reactions. The signs are: fever, flu-like symptoms (such as chills, body aches, shivering, and joint pain), nausea, vomiting, low blood pressure, high or low blood pressure, or low oxygen saturation in the blood that can cause difficulty breathing or shortness of breath, changes in heart rate, feeling strong palpitations in the chest or nervousness.
• Headache.
• ARIA. The signs of ARIA are: headache, confusion, dizziness, blurred vision, nausea, difficulty walking, or seizures (epileptic). One of the two main types of ARIA, ARIA-H, is associated with small areas of bleeding in the brain.

Up to 1 in 10 peoplemay experience the following side effects:

• Delayed allergic reactions. The signs are: rash, headache, runny nose, and hair loss.
• ARIA-E, associated with temporary fluid buildup in one or more regions of the brain.
• See the signs of ARIA above.
• Abnormal heart rhythm (this is called atrial fibrillation). The signs are: irregular heartbeat (rapid or accelerated pulses in the chest), chest pain, shortness of breath, dizziness, or feeling of fainting, tiredness, or difficulty exercising.
• Nausea.

Talk to your doctor about how to treat these side effects.

Reporting of side effects

If you experience any side effects, talk to your doctor, even if they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of LEQEMBI

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and label of the vial after "EXP". The expiry date is the last day of the month shown.
• Store in the original package to protect from light.
• Store in a refrigerator (between 2 °C and 8 °C). Do not freeze or shake.
• After dilution, the medicine should be used immediately. Chemical and physical stability has been demonstrated for 24 hours at 25 °C. From a microbiological point of view, unless the dilution method eliminates the risk of microbial contamination, the product should be used immediately. If not used immediately, in-use storage times and conditions are the responsibility of the user.

6. Container Contents and Additional Information

Composition of LEQEMBI

• The active ingredient is lecanemab. Each ml of concentrate contains 100 mg of lecanemab.
• The other components are water for injectable preparations, histidine hydrochloride monohydrate, arginine hydrochloride, and polysorbate 80.

Appearance and Container Contents of the Product

LEQEMBI is a concentrate for solution for infusion. Each box contains 1 vial of 2 ml of concentrate or 1 vial of 5 ml of concentrate. The concentrate is transparent to slightly opalescent and colorless to light yellow.

Only some pack sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Eisai GmbH

Edmund-Rumpler-Straße 3

60549 Frankfurt am Main

Germany

Email: [email protected]

You can request more information about this medicinal product by contacting the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

Other Sources of Information

Detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.

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This information is intended for healthcare professionals only:

Consult the dosage of the medicinal product in section 3.

Instructions for Preparation

LEQEMBI is for single use only.

LEQEMBI is a concentrate and must be diluted before infusion.

Dose Calculation

More than one vial of LEQEMBI concentrate may be necessary to administer the total dose to the patient.

The prescribed dose for the patient is administered in mg/kg (see section 3). Based on the prescribed dose, calculate the total dose to be administered.

The total dose of LEQEMBI in mg = patient weight in kg × prescribed dose in mg/kg.

The volume of LEQEMBI concentrate to prepare the dose (ml) = total dose in mg divided by 100 (the concentration of LEQEMBI concentrate is 100 mg/ml).

Preparation of LEQEMBI Infusion

Aseptic techniques must be used when preparing the diluted intravenous infusion solution of LEQEMBI.

• Check that the LEQEMBI liquid is transparent to slightly opalescent and colorless to light yellow.
• Remove the required volume of LEQEMBI from the vial (or vials) and add it to 250 ml of 0.9% sodium chloride injectable solution.
• Gently invert the infusion bag containing the diluted LEQEMBI solution to mix completely. Do not shake.
• It has been confirmed that infusion bags made of polypropylene, polyvinyl chloride, polyolefin/polyamide coextruded, or ethylene/propylene copolymer are compatible with the administration of lecanemab.
• After dilution, it is recommended to use the medicinal product immediately. Chemical and physical stability has been demonstrated for 24 hours at 25 °C. From a microbiological point of view, unless the dilution method eliminates the risk of microbial contamination, the product should be used immediately. If not used immediately, the in-use storage times and conditions are the responsibility of the user.
• Before infusion, allow the diluted LEQEMBI solution to reach room temperature.
• Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Method of Administration

LEQEMBI is for intravenous use only.

LEQEMBI is diluted before intravenous infusion (according to the preparation instructions above).

The diluted medicinal product should be inspected visually for particles or color changes before administration. Do not use if a color change or the presence of opaque particles is observed.

The diluted solution is infused over approximately 1 hour through an intravenous line. The use of a 0.2-micron sterile in-line filter with low protein binding (filter materials compatible: polytetrafluoroethylene, polyethersulfone, polycarbonate, polyvinylidene difluoride, polypropylene, polyurethane, and polysulfone) is recommended.