Nexviadyme

Patient Information Leaflet

Nexviadyme 100 mg powder for concentrate for infusion solution

avalglucosidase alfa
This medicinal product is subject to additional monitoring. This will allow rapid identification of
new safety information. You can help by reporting any side effects you experience while taking
this medicine. See the end of section 4 for information on how to report side effects.
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, consult your doctor, pharmacist or nurse.
• If you experience any side effect, including those not listed in this leaflet, consult your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Nexviadyme is and what it is used for
2. What you need to know before you are given Nexviadyme
3. How Nexviadyme is administered
4. Possible side effects
5. How to store Nexviadyme
6. Contents of the pack and other information

1. What Nexviadyme is and what it is used for

What Nexviadyme is
Nexviadyme contains an enzyme called avalglucosidase alfa, which is a copy of the natural enzyme,
called acid alpha-glucosidase, that is deficient in people with Pompe disease.

What Nexviadyme is used for
Nexviadyme is used to treat people of all ages with Pompe disease.
People with Pompe disease have reduced levels of an enzyme called acid alpha-glucosidase.
This enzyme helps regulate levels of glycogen (a type of carbohydrate) in the body. Glycogen provides energy to the body, but in Pompe disease, high levels of glycogen accumulate in various muscles and damage them.
This medicine replaces the missing enzyme so that the body can reduce glycogen accumulation.

2. What you should know before being given Nexviadyme

Do not use Nexviadyme
If you have previously experienced life-threatening allergic reactions (hypersensitivity) to
alglucosidase alfa or to any of the other components of this medicine (listed in
section 6), and these reactions reoccurred after stopping and restarting the medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Nexviadyme.
Immediately inform your doctor if treatment with Nexviadyme causes:

• allergic reactions, including anaphylaxis (a severe allergic reaction) – see section “Possible side effects” below for symptoms
• infusion-associated reactions during or within hours after administration of the medicine – see section “Possible side effects” below for symptoms.

If you have swelling in your lower limbs or widespread bruising, inform your doctor. Your doctor
will decide whether administration of Nexviadyme should be suspended and will initiate appropriate
medical treatment. Your doctor will also decide whether you can continue receiving avalglucosidase alfa.
Other medicines and Nexviadyme
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines.
Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you may be pregnant, are planning a pregnancy, or are breastfeeding,
consult your doctor or pharmacist before taking this medicine. There is no information available on the use of Nexviadyme in pregnant women. Nexviadyme
should not be administered during pregnancy unless your doctor recommends it.
You and your doctor will decide whether you can use Nexviadyme while breastfeeding.
Driving and using machines
Nexviadyme may have a minor effect on the ability to drive and use machines. Since dizziness, low blood pressure, and somnolence may occur as infusion-associated reactions, this could affect your ability to drive or operate machinery on the day of infusion.

3. How to take Nexviadyme

Nexviadyme must be administered exclusively under the supervision of a physician experienced in the treatment of Pompe disease.
You may be given other medicines before receiving Nexviadyme to reduce certain side effects. These medicines include an antihistamine, a corticosteroid, and a medicine (such as paracetamol) to reduce fever.
The dose of Nexviadyme is based on body weight and will be administered once every two weeks.

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

Home infusion
Your doctor may recommend home treatment with Nexviadyme if it is safe and convenient to do so. If an adverse reaction occurs during a Nexviadyme infusion, the home infusion personnel may stop the infusion and start appropriate medical treatment.

Instructions for correct use
Nexviadyme is administered via an intravenous infusion (a drip into a vein). It is supplied as a powder that must be mixed with sterile water and further diluted with glucose solution before infusion.

If you use more Nexviadyme than you should
Infusing Nexviadyme too quickly may cause flushing (hot flushes).

If you forget to take Nexviadyme
If an infusion is missed, contact your doctor. If you have any questions about the use of this medicine, speak with your doctor, pharmacist, or nurse.

If you stop treatment with Nexviadyme
Contact your doctor if you wish to stop treatment with Nexviadyme. Symptoms of the disease may worsen if you stop treatment.

4. Possible side effects

Side effects occur mainly during or shortly after administration of Nexviadyme.
You must inform your doctor immediately if you experience an infusion-related reaction or an allergic reaction.
Your doctor may prescribe you certain medicines before the infusion to prevent these reactions.

Infusion-related reactions
Most infusion-related reactions are mild or moderate in severity. Infusion-related reactions include symptoms such as chest discomfort, increased blood pressure, increased heart rate, chills, cough, diarrhoea, fatigue, headache, flu-like illness, nausea, vomiting, eye redness, pain in arms and legs, skin redness, skin itching, rash, and hives.

Allergic reactions
Allergic reactions may include symptoms such as difficulty breathing, chest tightness, flushing, cough, dizziness, nausea, redness of palms and soles, itching of palms and soles, swelling of the lower lip and tongue, low oxygen levels in the blood, and skin 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 (shaking)
• burning sensation
• eye redness
• eye itching
• eyelid swelling
• rapid heartbeat
• flushing
• increased blood pressure
• low blood pressure
• bluish discoloration of the skin and lips
• hot flush
• pale skin
• cough
• difficulty breathing
• throat irritation
• mouth and throat pain
• diarrhoea
• vomiting
• lip swelling
• swollen tongue
• abdominal pain
• upper abdominal pain
• indigestion
• hives
• redness of the hands
• skin redness
• red rash
• excessive sweating
• itchy rash
• skin plaque
• muscle spasms
• muscle pain
• pain in arm or leg
• flank pain
• fatigue
• chills
• fever
• chest discomfort
• pain
• flu-like illness
• infusion site pain
• low oxygen levels in the blood
• weakness
• facial swelling
• sensation of cold or heat

Uncommon (may affect up to 1 in 100 people)

• eye inflammation
• numbness or tingling
• increased tearing
• extra heartbeats
• rapid breathing
• throat swelling
• numbness of mouth, tongue or lip
• tingling of mouth, tongue or lip
• difficulty swallowing
• skin swelling
• skin color change
• facial pain
• increased body temperature
• leakage of fluid into surrounding tissue at the infusion site
• joint pain at the infusion site
• skin rash at the infusion site
• reaction at the infusion site
• itching sensation at the infusion site
• localized edema
• swelling of arms and legs
• abnormal breathing sounds (wheezing)
• blood test showing positive for inflammation
• reduced sensitivity to touch, pain, and temperature
• mouth discomfort (including burning sensation of the lips)

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

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist, or nurse.
You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 refers to the last day of that month.
Unopened vials
Store in a refrigerator (2 °C – 8 °C).
Reconstituted solution
After reconstitution, immediate use for dilution is recommended. The reconstituted solution can be stored in the refrigerator for up to 24 hours at 2 °C – 8 °C.
Diluted solution
After dilution, it is recommended to use the medicine immediately. The diluted solution can be stored for 24 hours at 2 °C – 8 °C, followed by 9 hours at room temperature (up to 25 °C).
Do not dispose of any medicine via wastewater or household waste. Ask your doctor, pharmacist, or nurse how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Nexviadyme contains
The active substance is avalglucosidase alfa. One vial contains 100 mg of avalglucosidase alfa. After
reconstitution, the solution contains 10 mg of alglucosidase alfa per mL and, following dilution,
the concentration ranges between 0.5 mg and 4 mg/mL.
The other components are:

• histidine
• monohydrate histidine hydrochloride
• glycine
• mannitol
• polysorbate 80

Description of the appearance of Nexviadyme 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. Not all pack sizes may be marketed.
The powder is white to pale yellow. After reconstitution, it forms a clear solution, colourless to pale
yellow. The reconstituted solution must be further diluted.
Marketing Authorisation Holder
Sanofi B.V.
Paasheuvelweg 25
1105 BP Amsterdam
The 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 Authorisation Holder:
België/Belgique/Belgien Lietuva
Sanofi Belgium Swixx Biopharma UAB
Tél/Tel: +32 2 710 54 00 Tel: +370 5 236 91 40
България Luxembourg/Luxemburg
Swixx Biopharma EOOD Sanofi Belgium
Тел.: +359 (0)2 4942 480 Tél/Tel: +32 2 710 54 00 (Belgique/Belgien)
Česká republika Magyarország
Sanofi s.r.o. SANOFI-AVENTIS Zrt.
Tel: +420 233086 111 Tel: +36 1 505 0050
Danmark Malta
Sanofi A/S Sanofi S.r.l.
Tlf: +45 45 16 70 00 Tel: +39 02 39394275
Deutschland Nederland
Sanofi-Aventis Deutschland GmbH Sanofi B.V.
Tel.: 0800 04 36 996 Tel: +31 20 245 4000
Tel. aus dem Ausland: +49 69 305 70 13
Eesti Norge
Swixx Biopharma OÜ sanofi-aventis Norge AS
Tel: +372 640 10 30 Tlf: +47 67 10 71 00
Ελλάδα Österreich
Sanofi-Aventis Μονοπρόσωπη AEBE sanofi-aventis GmbH
Τηλ: +30 210 900 1600 Tel: +43 1 80 185 – 0
España Polska
sanofi-aventis, S.A. Sanofi Sp. z o.o.
Tel: +34 93 485 94 00 Tel.: +48 22 280 00 00
France Portugal
Sanofi Winthrop Industrie Sanofi – Produtos Farmacêuticos, Lda. Tel: +351
Tél: 0 800 222 555 21 35 89 400
Appel depuis l’étranger: +33 1 57 63 23 23
Hrvatska România
Swixx Biopharma d.o.o. Sanofi Romania SRL
Tel: +385 1 2078 500 Tel: +40 (0) 21 317 31 36
Ireland Slovenija
Sanofi-aventis Ireland Ltd. T/A SANOFI Swixx Biopharma d.o.o.
Tel: +353 (0) 1 403 56 00 Tel: +386 1 235 51 00
Ísland Slovenská republika
Vistor hf. Swixx Biopharma s.r.o.
Sími: +354 535 7000 Tel: +421 2 208 33 600
Italia Suomi/Finland
Sanofi S.r.l. Sanofi Oy
Tel: 800536389 Puh/Tel: +358 201 200 300
Κύπρος Sverige
Sanofi AB
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741 Tel: +46 (0)8 634 50 00
Latvija United Kingdom (Northern Ireland)
Swixx Biopharma SIA sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +371 6 616 47 50 Tel: +44 (0) 800 035 2525
More detailed information on this medicinal product is available on the European Medicines Agency
website: http://www.ema.europa.eu/. Links to other websites on rare diseases and related therapeutic
treatments are also provided.
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The following information is intended exclusively for healthcare professionals:
Reconstitution
Use aseptic technique during reconstitution.

1. Determine the number of vials to reconstitute 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 (mg). Patient dose (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 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.
2. Remove the required number of vials needed for the infusion from the refrigerator and allow them to equilibrate to room temperature for approximately 30 minutes.
3. Reconstitute each vial by slowly injecting 10 mL of water for injections into each vial. Each vial will contain 100 mg/10 mL (10 mg/mL) of medicinal product. Add the water for injections avoiding direct spraying onto the lyophilised powder and avoid foaming. To achieve this, add the water for injections slowly, drop by drop, down the side of the vial. Then gently tilt and rotate each vial without inverting, shaking vigorously, or agitating.
4. Immediately inspect the reconstituted vials for particulate matter and discolouration. Do not use the product if particulate matter or discolouration is observed upon immediate inspection. Allow the solution to dissolve completely.

Dilution

5. The reconstituted solution must be diluted in 5% glucose in water to a final concentration between 0.5 mg/mL and 4 mg/mL. See Table 1 for the recommended total infusion volume based on patient weight.
6. Slowly withdraw from each vial the volume of reconstituted solution (calculated based on patient weight).
7. Add the reconstituted solution slowly and directly into the 5% glucose solution. Avoid foaming or agitation of the infusion bag. Avoid introducing air into the infusion bag.
8. Invert or gently massage the infusion bag to mix. Do not shake.
9. To avoid administration of particles inadvertently introduced during dose preparation, it is recommended to administer Nexviadyme using a low-protein-binding 0.2 μm in-line filter. At the end of the infusion, flush the intravenous line with 5% glucose in water.
10. Do not infuse Nexviadyme in the same intravenous line with other medicinal products.

Table 1. Expected intravenous infusion volumes for administration of Nexviadyme based on patient weight at doses of 20 and 40 mg/kg

| Patient weight range (kg) | Total infusion volume (ml) for 20 mg/kg | Total infusion volume (ml) for 40 mg/kg | |---------------------------|----------------------------------------|----------------------------------------| | 1.25 to 5 | 50 | 50 | | 5.1 to 10 | 50 | 100 | | 10.1 to 20 | 100 | 200 | | 20.1 to 30 | 150 | 300 | | 30.1 to 35 | 200 | 400 | | 35.1 to 50 | 250 | 500 | | 50.1 to 60 | 300 | 600 | | 60.1 to 100 | 500 | 1,000 | | 100.1 to 120 | 600 | 1,200 | | 120.1 to 140 | 700 | 1,400 | | 140.1 to 160 | 800 | 1,600 | | 160.1 to 180 | 900 | 1,800 | | 180.1 to 200 | 1,000 | 2,000 |

The unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with local regulations.
Home infusion
Home infusion of Nexviadyme may be considered for patients who tolerate infusions well and have no history of moderate or severe IARs for several months. The decision to proceed with home infusion for a patient must be made following evaluation and recommendation by the physician. When assessing patient suitability for home infusion, underlying comorbidities and the ability to adhere to home infusion requirements should be considered. The following criteria should be taken into account:

• The patient must not have any current concomitant condition that, in the physician’s judgment, could affect the patient’s ability to tolerate the infusion.
• The patient is considered clinically stable. A comprehensive assessment must be performed prior to initiating home infusion.
• The patient must have received Nexviadyme infusions for several months under the supervision of a physician experienced in managing patients with Pompe disease, which may occur in a hospital or another appropriate outpatient setting. Documentation of a pattern of well-tolerated infusions in the absence of IARs or with only mild IARs controlled by premedication is a prerequisite for initiating home infusion.
• The patient must agree to undergo treatment at home and must be able to adhere to home infusion procedures.
• Infrastructure, resources, and procedures for home infusion, including training, must be defined and made available to the healthcare provider. The healthcare provider must be available at all times during the entire duration of the home infusion and for a specified period after the infusion, depending on the patient’s tolerance prior to initiating home infusion.

If the patient experiences adverse reactions during home infusion, the infusion procedure must be stopped immediately and appropriate medical treatment initiated (see section 4.4). Subsequent infusions may need to be administered in a hospital or appropriate outpatient setting until no adverse reactions occur. The dose and infusion rate must not be modified without consulting the responsible physician.