Prospect: information for the user

Nexviadyme100 mg powder for concentrate for solution for infusion

avalglucosidase alfa

This medicine is subject to additional monitoring, which will speed up the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

What isNexviadyme

Nexviadyme contains an enzyme called avalglucosidase alfa; it is a copy of the natural enzyme called acid alpha-glucosidase (GAA) that is lacking in people with Pompe disease.

What is it used forNexviadyme

Nexviadyme is used to treat people of all ages who have Pompe disease.

People with Pompe disease have low levels of the acid alpha-glucosidase (GAA) enzyme. This enzyme helps control glycogen (a type of carbohydrate) levels in the body. Glycogen provides energy to the body, but in Pompe disease, high levels of glycogen accumulate in various muscles and damage them. The medication replaces the missing enzyme so that the body can reduce glycogen accumulation.

Do not useNexviadyme

If you have had potentially fatal allergic reactions (hypersensitivity) toavalglucosidase alfaor to any of the other components of this medication (listed in section6) and these reactions occurred again after interrupting and restarting the medication.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to use 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
• reaction associated with infusion while receiving the medication or in the few hours that follow - 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 if you should stop the infusion of Nexviadyme and give you the appropriate medical treatment. Your doctor will also decide if you can continue to receive avalglucosidase alfa.

Other medications andNexviadyme

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication. There is no information on the use of Nexviadyme in pregnant women. Do not receive Nexviadyme during pregnancy unless your doctor specifically recommends it. You and your doctor should decide if you can use Nexviadyme if you are breastfeeding.

Driving and operating machinery

Nexviadyme may have a minor effect on your ability to drive and operate machinery. Since dizziness, low blood pressure, and drowsiness may occur as infusion-related reactions, this may affect your ability to drive and operate machinery on the day of infusion.

Nexviadyme will be administered under the supervision of a healthcare professional with experience in treating Pompe disease.

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

The dose of Nexviadyme is based on your weight and will be administered once every 2 weeks.

• The recommended dose of Nexviadyme is 20 mg/kg of 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 have any side effects during a Nexviadyme infusion, the home infusion administrator may interrupt the infusion and start the appropriate medical treatment.

Instructions for proper use

Nexviadyme is administered through a drip in a vein (intravenous infusion). It is supplied to the healthcare professional in the form of powder to mix with sterile water and then dilute with glucose before infusion.

If you receive more Nexviadyme than you should

A high infusion rate of Nexviadyme may cause hot flashes.

If you forget your dose of Nexviadyme

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

If you interrupt treatment with Nexviadyme

Consult with your doctor if you want to interrupt treatment with Nexviadyme. Your disease symptoms may worsen if you interrupt treatment.

Adverse effects occur mainly while patients are receiving the Nexviadyme infusion or shortly after. Inform your doctor immediately if you experience a reaction associated with the infusion or an allergic reaction. Your doctor may give you medications before your infusion to prevent these reactions.immediatelyif you experience a reaction associated with the infusion or an allergic reaction. Your doctor may give you medications before your infusion to prevent these reactions.

Reactions associated with the infusion

Most reactions associated with the infusion are mild or moderate. Symptoms of the infusion reaction include chest discomfort, increased blood pressure, increased heart rate, chills, cough, diarrhea, fatigue, headache, flu-like illness, nausea, vomiting, red eyes, arm and leg pain, skin redness, skin itching, skin rash, and hives.

Allergic reactions

Allergic reactions may include symptoms such as difficulty breathing, chest pressure, flushing, cough, dizziness, nausea, red palms and feet, skin itching, lip and tongue swelling, low oxygen levels in the blood, and skin rash.

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

• Hypersensitivity
• Headache
• Nausea
• Skin itching
• Skin rash

Common(may affect up to 1 in 10 people)

• Anaphylaxis (severe allergic reaction)
• Dizziness
• Somnolence
• Tremor (agitation)
• Burning sensation
• Red eyes
• Eye itching
• Swollen eyelid
• Palpitations
• Flushing
• Increased blood pressure
• Low blood pressure
• Skin turns blue
• Hot flashes
• Pale skin
• Cough
• Difficulty breathing
• Throat irritation
• Mouth and throat pain
• Diarrhea
• Vomiting
• Swollen lips
• Swollen tongue
• Abdominal pain
• Upper abdominal pain
• Indigestion
• Hives
• Red hands
• Red skin
• Red skin rash
• Excessive sweating
• Skin rash with itching
• Skin plaque
• Muscle spasms
• Muscle pain
• Arm or leg pain
• Side pain
• Fatigue
• Chills
• Fever
• Chest discomfort
• Pain
• Flu-like illness
• Pain at the infusion site
• Low oxygen levels in the blood
• Weakness
• Swollen face
• Reduced sensation to touch, pain, and temperature
• Oral discomfort (including burning sensation in the lips)

Uncommon(may affect up to 1 in 100 people)

• Eye inflammation
• Numbness or tingling
• Excessive tearing
• Extra heartbeats
• Fast breathing
• Swollen throat
• Numbness in the mouth, tongue, or lips
• Tingling in the mouth, tongue, or lips
• Difficulty swallowing
• Swollen skin
• Skin discoloration
• Facial pain
• Increased body temperature
• Extravasation at the infusion site
• Painful joints at the infusion site
• Rash at the infusion site
• Reaction at the infusion site
• Itching at the infusion site
• Localized edema
• Swollen arms and legs
• Abnormal respiratory sounds (wheezing)
• Blood test for inflammation
• Reduced sensation to touch, pain, and temperature
• Oral discomfort (including burning sensation in the lips)

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor,pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting adverse effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the label after CAD. The expiration date is the last day of the month indicated.

Unopened vials:

Store in the 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 the refrigerator between 2°C and 8°C.

Diluted solution:

After dilution, it is recommended to use immediately.The diluted solution can be stored for 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 through drains or in the trash. Ask your doctor, pharmacist, or nurse how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition ofNexviadyme

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

The other components are:

• Histidine
• Monohydrate hydrochloride of histidine
• Glycine
• Mannitol
• Polysorbate 80

Appearance of the product and contents of the pack

Avalglucosidase alfa is a powder for concentrate for solution for infusion in a vial (100 mg/vial). Each pack 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 transparent, colorless to pale yellow solution. The reconstituted solution must be diluted further.

Marketing Authorization Holder

Sanofi B.V.

Paasheuvelweg 25

1105 BP Amsterdam

Netherlands

Manufacturer

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

Further information on this medicinal product can be obtained by contacting the local representative of the marketing authorization holder:

Last update of this leaflet:

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

<------------------------------------------------------------------------------------------------------------------>

This information is intended solely for healthcare professionals:

Reconstitution:

Use an aseptic technique during reconstitution.

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

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

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

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

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

2.Remove the required number of vials from the refrigerator and wait for approximately 30 minutes to allow them to reach room temperature.

3.Reconstitute each vialby slowly injecting 10.0 ml of water for injection (water for injection,WFI,by its English acronym) into each vial. Each vial will result in 100 mg/10 ml (10 mg/ml).Avoid violent 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. Inclineand gently rotate each vial. Do not invert, turn or shake.

4.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 during the immediate inspection or if the solution has changed color, do not use it. Allow the solution to dissolve.

Dilution

1.The reconstituted solution must be diluted in 5% glucose solution in water to a final concentration of 0.5 mg/ml to 4 mg/ml. See Table 1 to know the recommended total infusion volume based on the patient's weight.

2.Slowly extract the volume of the reconstituted solution from each vial (calculated based on the patient's 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.Invert the infusion bag carefully or massage it to mix. Do not shake.

5.To avoid administering particles inadvertently introduced during the preparation of the IV dose, it is recommended to use a 0.2 μm in-line filter with low plasma protein binding to administer Nexviadyme. Once the infusion is complete, wash the intravenous line with 5% glucose solution in water.

6.Do not administer Nexviadyme in the same intravenous line with other medications.

Table 1: Estimated infusion volumes for the administration of Nexviadyme by patient weight at doses of 20 mg/kg and 40 mg/kg

The disposal of unused medicinal product and all materials that have been in contact with it will be carried out in accordance with local regulations.

Home Infusion

Consider home infusion ofNexviadymefor patients with good tolerance to infusions and no history of moderate or severe RAPs for some 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 the requirements of home infusion should be taken into account when evaluating the patient's eligibility for home infusion. The following criteria should be considered:

• The patient should not have a concurrent condition that, in the opinion of the physician, may affect the patient's ability to tolerate the infusion.
• The patient is considered medically stable. A detailed evaluation should be completed before starting home infusion.
• The patient has received supervised infusions ofNexviadymeby a physician withexperience in treating Pompe patients for some months that may be either in a hospital or an appropriate ambulatory care setting. Documentation of a pattern of well-tolerated infusions withoutRAPs, orRAPsthat have been controlled with previous medication, is a prerequisite for starting home infusion.
• The patient is willing and able to comply with the procedures of home infusion.
• The infrastructure, resources, and procedures for home infusion, including training, should be established and available for the healthcare professional. The healthcare professional should be available at all times during home infusion and for a specified period after infusion, based on the patient's 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 either in a hospital or an appropriate ambulatory care setting until such adverse reactions do not occur. The dose and infusion rate should not be changed without consulting the patient's treating physician.