NEXVIADYME 100 mg POWDER FOR CONCENTRATE FOR PERFUSION SOLUTION

2. What you need to know before you are given Nexviadyme

Do not useNexviadyme

If you have had potentially life-threatening allergic reactions (hypersensitivity) to avalglucosidase alfa or to any of the other components of this medicine (listed in section 6) and these reactions occurred again after stopping and restarting the medicine.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start using Nexviadyme.

Contact your doctor immediately if treatment with Nexviadyme causes:

• allergic reactions, including anaphylaxis (a severe allergic reaction) - see the section "Possible side effects" below for symptoms
• infusion-associated reaction while you are receiving the medicine or in the few hours following - see the section "Possible side effects" below for symptoms

Also, inform your doctor if you have swelling in your legs or generalized swelling of your body. Your doctor will decide whether to stop the infusion of Nexviadyme and start the appropriate medical treatment. Your doctor will also decide whether you can continue to receive avalglucosidase alfa.

Other medicines andNexviadyme

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine. There is no information on the use of Nexviadyme in pregnant women. You should not receive Nexviadyme during pregnancy unless your doctor specifically recommends it. Your doctor and you must decide whether you can use Nexviadyme if you are breastfeeding.

Driving and using machines

Nexviadyme may have a minor effect on your ability to drive and use machines. Since dizziness, low blood pressure, and somnolence can occur as infusion-associated reactions, this may affect your ability to drive and use machines on the day of infusion.

3. How Nexviadyme is given

Nexviadyme will be given to you under the supervision of a healthcare professional with experience in the treatment of Pompe disease.

You may be given other medicines before receiving Nexviadyme to reduce some side effects. These medicines include an antihistamine, a steroid, and a medicine (such as paracetamol) to reduce fever.

The dose of Nexviadyme is based on your weight and will be given to you every 2 weeks.

• The recommended dose of Nexviadyme is 20 mg/kg body weight.

Home infusion

Your doctor may consider that you can receive home infusion of Nexviadyme if it is safe and convenient to do so. If you experience any side effects during a Nexviadyme infusion, the person responsible for the home infusion can stop the infusion and start the appropriate medical treatment.

Instructions for proper use

Nexviadyme is given by drip into a vein (intravenous infusion). It is supplied to the healthcare professional as a powder to be mixed with sterile water and then diluted with glucose before infusion.

If you receive moreNexviadymethan you should

A too-fast infusion rate of Nexviadyme can cause flushing.

If you miss a dose ofNexviadyme

If you have missed an infusion, contact your doctor. If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

If you stop treatment withNexviadyme

Talk to your doctor if you want to stop treatment with Nexviadyme. The symptoms of your disease may worsen if you stop treatment.

4. Possible side effects

Side effects mainly occur while patients are receiving the Nexviadyme infusion or soon after. You should tell your doctor immediately if you experience an infusion-associated reaction or an allergic reaction. Your doctor may give you medicines before your infusion to prevent these reactions.

Infusion-associated reactions

Most infusion-associated reactions are mild or moderate. The symptoms of an infusion-associated reaction include chest discomfort, increased blood pressure, increased heart rate, chills, cough, diarrhea, fatigue, headache, flu-like illness, nausea, vomiting, red eyes, pain in arms and legs, skin redness, skin itching, rash, and hives.

Allergic reactions

Allergic reactions can include symptoms such as difficulty breathing, chest pressure, redness, cough, dizziness, nausea, redness of the palms and soles, itching of the palms and soles, swelling of the lower lip and tongue, low oxygen level in the blood, and rash.

Very common(may affect more than 1 in 10 people)

• Hypersensitivity
• Headache
• Nausea
• Skin itching
• Rash

Common(may affect up to 1 in 10 people)

• Anaphylaxis (severe allergic reaction)
• Dizziness
• Somnolence
• Tremor (shakiness)
• Burning sensation
• Red eyes
• Itching in the eyes
• Swelling of the eyelid
• Pounding heartbeat
• Redness
• Increased blood pressure
• Low blood pressure
• Blue discoloration of the skin and lips
• Flushing
• Pale skin
• Cough
• Difficulty breathing
• Sore throat
• Mouth and throat pain
• Diarrhea
• Vomiting
• Swelling of the lips
• Swollen tongue
• Abdominal pain (stomach pain)
• Upper abdominal pain (stomach pain)
• Indigestion
• Hives
• Redness of the hands
• Redness of the skin
• Red rash
• Excessive sweating
• Itchy rash
• Skin plaque
• Muscle spasms
• Muscle pain
• Pain in arms or legs
• Side pain
• Fatigue
• Chills
• Fever
• Chest discomfort
• Pain
• Flu-like illness
• Pain at the infusion site
• Low oxygen level in the blood
• Weakness
• Swelling of the face
• Feeling of cold or heat

Uncommon(may affect up to 1 in 100 people)

• Eye inflammation
• Numbness or tingling
• Watery eyes
• Extra heartbeats
• Rapid breathing
• Swelling of the throat
• Numbness or tingling in the mouth, tongue, or lips
• Difficulty swallowing
• Swelling of the skin
• Discoloration of the skin
• Facial pain
• Increased body temperature
• Leakage at the infusion site
• Joint pain at the infusion site
• Rash at the infusion site
• Reaction at the infusion site
• Itching at the infusion site
• Localized swelling
• Swelling in the arms and legs
• Abnormal breathing sounds (wheezing)
• Blood tests for inflammation
• Reduced sensation to touch, pain, and temperature
• Mouth discomfort (including burning sensation in the lips)

Side effects reported in children and adolescents were similar to those observed in adults.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is possible side effects 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. Storing Nexviadyme

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 label after EXP. The expiry date is the last day of the month shown.

Unopened vials:

Store in a refrigerator (between 2°C and 8°C).

Reconstituted solution:

After reconstitution, it is recommended to dilute immediately. The reconstituted solution can be stored for up to 24 hours when kept in a refrigerator between 2°C and 8°C.

Diluted solution:

After dilution, it is recommended to use immediately. The diluted solution can be stored for up to 24 hours at a temperature between 2°C and 8°C, followed by 9 hours at room temperature (up to 25°C).

Medicines should not be disposed of via wastewater or household waste. Ask your doctor, pharmacist, or nurse how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Container Contents and Additional Information

Composition ofNexviadyme

The active substance is avalglucosidase alfa. One vial contains 100 mg of avalglucosidase alfa. After reconstitution, the solution contains 10 mg of avalglucosidase alfa per ml and, after dilution, the concentration ranges from 0.5 mg/ml to 4 mg/ml.

The other components are:

• Histidine
• Hydrochloride histidine monohydrate
• Glycine
• Mannitol
• Polysorbate 80

Appearance of the Product and Container Contents

Avalglucosidase alfa is a powder for concentrate for solution for infusion in a vial (100 mg/vial). Each container contains 1, 5, 10, or 25 vials. Only some pack sizes may be marketed.

The powder is white to pale yellow in color. After reconstitution, it is a clear, colorless to pale yellow solution. The reconstituted solution must be diluted subsequently.

Marketing Authorization Holder

Sanofi B.V.

Paasheuvelweg 25

1105 BP Amsterdam

Netherlands

Manufacturer

Genzyme Ireland Limited, IDA Industrial Park, Old Kilmeaden Road, Waterford, Ireland

For further information on this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Prospectus:

Detailed information on this medicinal product is available on the European Medicines Agency website: http://www.ema.europa.eu. There are also links to other websites on rare diseases and orphan medicines.

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This information is intended for healthcare professionals only:

Reconstitution:

Use aseptic technique during reconstitution.

1. Calculate the number of vials needed for reconstitution based on the individual patient's weight and the recommended dose of 20 mg/kg or 40 mg/kg.

Patient weight (kg) × dose (mg/kg) = patient dose (in mg). Patient dose (in mg) divided by 100 mg/vial = number of vials to be reconstituted. If the number of vials includes a fraction, round up to the next whole number.

Example: patient weight (16 kg) × dose (20 mg/kg) = patient dose (320 mg). 320 mg divided by 100 mg/vial = 3.2 vials; therefore, 4 vials must be reconstituted.

Example: patient weight (16 kg) × dose (40 mg/kg) = patient dose (640 mg).

640 mg divided by 100 mg/vial = 6.4 vials; therefore, 7 vials must be reconstituted.

1. Remove the required number of vials for infusion from the refrigerator and wait for approximately 30 minutes to allow them to reach room temperature.
2. Reconstitute each vial by slowly injecting 10.0 ml of water for injection (WFI) into each vial. Each vial will yield 100 mg/10 ml (10 mg/ml). Avoid vigorous impact of WFI on the powder and foam formation. This is achieved by slowly adding the water for injection through the inner wall of the vial and not directly onto the lyophilized powder. Tilt and gently rotate each vial. Do not invert, turn, or shake.
3. Perform an immediate visual inspection of the reconstituted vials to check that the solution does not contain particles or has changed color. If particles are observed or the solution has discolored during the immediate inspection, do not use it. Allow the solution to dissolve.

Dilution

1. The reconstituted solution must be diluted in 5% glucose in water to a final concentration of 0.5 mg/ml to 4 mg/ml. Refer to Table 1 for the recommended total infusion volume based on patient weight.
2. Slowly withdraw the calculated volume of the reconstituted solution from each vial (based on patient weight).
3. Add the reconstituted solution slowly and directly to the 5% glucose solution. Avoid foam formation or agitation of the infusion bag. Avoid introducing air into the infusion bag.
4. Gently invert or massage the infusion bag to mix. Do not shake.
5. To avoid administration of inadvertently introduced particles during IV dose preparation, it is recommended to use a 0.2 μm low protein-binding in-line filter to administer Nexviadyme. After completion of the infusion, flush the intravenous line with 5% glucose in water.
6. Do not administer Nexviadyme in the same intravenous line with other medicinal products.

Table 1: Estimated Intravenous Infusion Volumes for Administration of Nexviadyme by Patient Weight at Doses of 20 mg/kg and 40 mg/kg

Disposal of unused medicinal product and all materials that have come into contact with it should be done in accordance with local regulations.

Home Infusion

Home infusion of Nexviadyme should be considered for patients with good tolerance to infusions and who have not had a history of moderate or severe RAPs for several months. The decision to switch the patient to home infusion should be made after evaluation and recommendation by the patient's treating physician. The patient's underlying comorbidities and ability to comply with home infusion requirements should be taken into account when assessing patient eligibility for home infusion. The following criteria should be considered:

• The patient should not have a concurrent condition that, in the physician's opinion, may affect the patient's ability to tolerate the infusion.
• The patient is considered medically stable. A detailed assessment should be completed before initiating home infusion.
• The patient should have received supervised Nexviadyme infusions by a physician experienced in the treatment of Pompe patients for several months, which may be in a hospital or other suitable setting for outpatient care. Documentation of a well-tolerated infusion pattern without RAPs, or mild RAPs that have been controlled with premedication, is a prerequisite for initiating home infusion.
• The patient must be willing and able to comply with home infusion procedures.
• The infrastructure, resources, and procedures for home infusion, including training, should be established and available to the healthcare professional. The healthcare professional should be available at all times during home infusion and for a certain period after infusion, depending on the patient's prior tolerance before starting home infusion.

If the patient experiences adverse reactions during home infusion, the infusion process should be interrupted immediately, and appropriate medical treatment should be initiated. It may be necessary to perform subsequent infusions in a hospital or other suitable setting for outpatient care until such an adverse reaction no longer occurs. The dose and infusion rate should not be changed without consulting the patient's treating physician.