InfoCons Consumer Protection informs you – Xenpozyme – Package Leaflet

Before anything else

Read all of this leaflet carefully before you are given this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or nurse.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

ℹ️ 1. What Xenpozyme is and what it is used for

What Xenpozyme is Xenpozyme contains an enzyme called olipudase alfa.

What Xenpozyme is used for

Xenpozyme is used to treat an inherited disorder called acid sphingomyelinase deficiency (ASMD). It is used in children and adults with ASMD types A/B or B to treat the signs and symptoms of ASMD not related to the brain.

How Xenpozyme works

Patients with ASMD lack a properly working version of the enzyme acid sphingomyelinase. This results in build -up of a substance called sphingomyelin, which damages organs such as spleen, liver, heart, lungs and blood. Olipudase alfa acts in the same way as the natural enzyme would , and so acts as a replacement, reducing the build -up of sphingomyelin in the organs and treating the signs a nd symptoms .

⚠️ 2. What you need to know before you are given Xenpozyme

You must not be given Xenpozyme

• If you have experienced life -threatening allergic ( anaphylactic ) reactions to olipudase alfa (see section ‘Warnings and precautions’ below) or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions

You may have side effects called infusion -associated reactions (IARs) that may be caused by the infusion (drip) of the medicine. They may occur while you are being given Xenpozyme or within 24 hours after the infusion.

40 They may include allergic reactions (see section 4) and symptoms such as headache, a raised, itchy rash ( hives ), fever, nausea, vomiting and itchy skin.

If you think you are having an IAR, tell your doctor straight away.

If you have a severe allergic reaction during your infusion your doctor will stop your infusion and provide appropriate medical treatment. Your doctor will make a judgement about the risks and benefits of giving you further doses Xenpozyme .

If you have a mild or moderate IAR, your doctor or nurse may temporarily stop the infusion, lower the infusion rate, and/or reduce the dose.

Your doctor may also give (or have given) you other medicines to prevent or manage allergic reaction s.

Your doctor will order blood tests to check how well your liver is working ( by measuring levels of your liver enzymes) before starting the treatment, and then at regular intervals as the doses are adjusted (see section 3 ).

Other medicines and Xenpozyme

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

Pregnancy and breast -feeding If you are pregnant or breast -feeding, think you may be pregnant, or are planning to have a baby, ask your doctor or nurse for advice before using this medicine.

There is limited experience with the use of Xenpozyme in pregnant women. Xenpozyme may be harmful to unborn children when taken by a woman during pregnancy . Xenpozyme should only be used during pregnancy if clearly necessary . Women who are able to become pregnant should use effective contraception during treatment and for 14 days after the last dose if Xenpozyme is discontinued .

It is not known whether Xenpozyme passes into human breast milk. Xenpozyme was detected in animal milk. Tell your doctor if you are breast -feeding or plan to do so. Your doctor will then help you decide whether to stop breast -feeding, or whether to stop taking Xenpozyme, considering the benefit of breast -feeding the baby and the benefit of Xenpozyme to the m other .

Driving and using machines

Xenpozyme may have a minor influence on the ability to drive and use machines because you may experience low blood pressure (which may make you feel faint) .

Xenpozyme contains sodium

This medicine contains 0.60 mg sodium (main component of cooking/table salt) per 4 mg vial or 3.02 mg sodium per 20 mg vial. This is equivalent to 0.03% and 0.15% , respectively, of the recommended maximum daily dietary intake of sodium for an adult or an adolescent and ≤0.08% and ≤ 0.38%, respectively, of the maximum acceptable daily intake of sodium for child ren below 16 years of age .

💊 3. How Xenpozyme is given

Xenpozyme will be given to you as a drip (infusion) under the supervision of a healthcare professional who is experienced in the treatment of ASMD or other metabolic diseases.

The dose you receive is based on your body weight and will be given to you every two weeks.

Treatment starts with a low dose of the medicine, which is gradually increased.

Infusion usually lasts around 3 to 4 hours but may be shorter or longer based on your doctor’s judgement , and may be shorter during the period whilst your dose is being increased .

41 Adult patients The recommended starting dose of Xenpozyme is 0.1 mg for each kg of body weight. This is increased in a planned way with each subsequent dose, until the recommended dose of 3 mg for each kg of body weight every 2 weeks is reached . It typically takes up to 14 weeks to reach the recommended dose but may be longer based on your doctor’s judgement.

Children

The recommended starting dose of Xenpozyme is 0.03 mg for each kg of body weight. The subsequent doses should be increased in a planned way up to the recommended dose of 3 mg for each kg of body weight every 2 weeks. It typically takes up to 16 weeks to reach the recommended dose but may be longer based on your doctor’s judgement.

Home infusion Your doctor may consider home infusion of Xenpozyme if you are on stable dose and tolerating your infusions well. This decision to move to home infusion should be made after evaluation and recommendation by your doctor . If you get a side effect during an infusion of Xenpozyme , the person giving your home infusion may stop the infusion and start appropriate medical treatment.

Instructions for proper use Xenpozyme is given by intravenous infusion (a drip into a vein) . It is supplied as a powder that will be mixed with sterile water before it is given.

If you are given more Xenpozyme than you should

Tell your doctor immediately , if you suspect a change from your routine infusion .

If you miss a Xenpozyme infusion It is important to have your infusion every 2 weeks. An infusion is considered missed if not given within 3 days from the scheduled infusion. Depending on the number of missed doses, you r doctor may have to restart from a lowe r dose.

If you have missed an infusion or are unable to attend a scheduled appointment, please contact your doctor right away.

If you have any further questions on the use of this medicine, ask your doctor or nurse.

❗ 4. Possible side effects

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

Infusion -associated reactions (IARs) have been seen while patients were being given the medicine or within 24 hours after the infusion.

The most serious side effects may include sudden severe allergic reactions, raised, itchy rash ( hives ), rash, increased liver enzymes and irregular heartbeat.

You must tell your doctor immediately if you get an IAR or an allergic reaction.

If you have an infusion reaction you may be given additional medicines to treat or help prevent future reactions. If the infusion reaction is severe, your doctor may stop the infusion of Xenpozyme and start giving appropriate medical treatment.

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

• Headache
• Raised, itchy rash ( hives)
• Fever – body temperature increased
• Nausea
• Abdominal (belly) pain
• Vomiting 42 • Itchy skin
• Muscles aches
• Rash
• Increased blood test for inflammation
• Pain in upper belly
• Reddening of the skin

Common (may affect up to 1 in 10 people )

• Itchy or red eyes
• Joint pain
• Fatigue
• Abnormal blood test for liver function
• Diarrhoea
• Low blood pressure
• Difficulty breathing
• Abdominal discomfort
• Rash (different types of rash sometimes with itch)
• Back pain
• Pain
• Chills
• Feeling very warm
• Wheezing
• Throat and voice box irritation
• Liver pain
• Skin lesions (such as solid elevated or red flat lesions)
• Bone pain
• Weakness
• Severe allergic reactions
• Eye discomfort
• Fast heartbeat
• Forceful heartbeat that may be rapid or irregular
• Throat tightness and swelling
• Stomach pain
• Rapid swelling under the skin in areas such as the face, throat, arms and legs which can be life threatening if throat swelling blocks the airway
• Catheter site -related reactions including pain, itching, or swelling
• Abnormal blood test for inflammation

Reporting of side effects

If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via 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. How to store Xenpozyme

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

Do not use Xenpozyme after the expir y date stated on the label and the carton . The expiry date refers to the last day of the month.

Store in refrigerator between 2°C to 8°C.

43 After dilution, immediate use is recommended.

If not used immediately, the reconstituted solution may be stored for up to 24 hours at 2°C to 8°.

After dilution, the solution can be stored for up to 24 hours at 2 -8°C followed by 12 hours (including infusion time) at room temperature.

Do not throw away any medicines via wastewater or household waste. Ask your doctor or nurse how to throw away medicines you no longer use. These measures will help protect the environment.

📦 6. Contents of the pack and other information

What Xenpozyme contains

• The active substance is olipudase alfa. One vial contains 4 mg or 20 mg of olipudase alfa.
• Other ingredients are
• L-methionine
• Sodium phosphate dibasic heptahydrate
• Sodium phosphate monobasic monohydrate
• Sucrose

see section 2 Xenpo zyme contains sodium

What Xenpozyme looks like and contents of the pack

Xenpozyme is a powder for concentrate for solution for infusion in a vial ( 4 or 20 mg/vial).

The powder is white to off -white lyophili sed powder.

After mixing with sterile water, it is a clear, colorless solution. The solution must be further diluted before infusion.

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 any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 Lietuva Swixx Biopharma UAB Tel: +370 5 236 91 40 България Swixx Biopharma EOOD Тел.: +359 (0)2 4942 480 Luxembourg/Luxemburg Sanofi Belgium Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien) Česká republika Sanofi, s.r.o.

Tel: +420 233 086 111 Magyarország SANOFI -AVENTIS Zrt.

Tel.: +36 1 505 0050 Danmark Sanofi A/S Tlf: +45 45 16 70 00 Malta Sanofi S.r.l.

Tel: +39 02 39394275 Deutschland Sanofi -Aventis Deutschland GmbH Tel.: 0800 04 36 996 Tel. aus dem Ausland: +49 69 305 70 13 Nederland Sanofi B.V.

Tel: + 31 20 245 4000 Eesti Swixx Biopharma OÜ Tel: +372 640 10 30 Norge sanofi -aventis Norge AS Tlf: +47 67 10 71 00 Ελλάδα Sanofi -Aventis Μονοπρόσωπη AEBE Τηλ: +30 210 900 16 00 Österreich sanofi -aventis GmbH Tel: +43 1 80 185 – 0 España sanofi -aventis, S.A.

Tel: +34 93 485 94 00 Polska Sanofi Sp. z o.o.

Tel.: +48 22 280 00 00 France Sanofi Winthrop Industrie Tél: 0 800 222 555 Appel depuis l’étranger : +33 1 57 63 23 23 Portugal Sanofi – Produtos Farmacêuticos, Lda Tel: +351 21 35 89 400 Hrvatska Swixx Biopharma d.o.o.

Tel: +385 1 2078 500 România Sanofi Romania SRL Tel: +40 (0) 21 317 31 36 Ireland sanofi -aventis Ireland Ltd. T/A SANOFI Tel: +353 (0) 1 403 56 00 Slovenija Swixx Biopharma d.o.o.

Tel: +386 1 235 51 00 Ísland Vistor ehf.

Sími: +354 535 7000 Slovenská republika Swixx Biopharma s.r.o.

Tel: +421 2 208 33 600 Italia Sanofi S.r.l.

Tel: 800 536389 Suomi/Finland Sanofi Oy Puh/Tel: +358 (0) 201 200 300 Κύπρος C.A. Papaellinas Ltd.

Τηλ: +357 22 741741 Sverige Sanofi AB Tel: +46 (0)8 634 50 00 Latvija Swixx Biopharma SIA Tel: +371 6 616 47 50

This leaflet was last revised i n

Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: http://www.ema.europa.eu . There are also links to other websites about rare diseases and treatments.

This leaflet is available in all EU /EEA languages on the European Medicines Agency website and on the website : www. xenpozyme.info.sanofi , or by scanning the QR code below (also included on the outer carton ) with a smartphone. <placeholder for QR code> <——————————————————————————————— ————————— >

🩺 Information intended for healthcare professionals only

Preparation of the dosing solution The powder for concentrate for solution for infusion must be reconstituted with sterile water for injection, diluted with sodium chloride 9 mg/mL (0.9%) solution for injection and then administered by intravenous infusion.

The reconstitution and dilution steps must be completed under aseptic conditions. Filtering devices should not be used at any time during the preparation of the infusion solution. Avoid foaming during reconstitution and dilution steps.

1) Determine the number of vials to be reconstituted based on the individual patient’s weight and the prescribed dose.

Patient weight (kg) × dose (mg/kg) = patient dose (in mg). For example, when using 20 mg vials, patient dose (in mg) divided by 20 mg/vial = number of vials to reconstitute. If the number of vials includes a fraction, round up to the next whole number.

2) Remove the required number of vials from refrigeration and set aside for approximately 20 to 30 minutes to allow them to reach room temperature.

3) Reconstitute each vial by injecting :

1.1 mL of sterile water for injection into the 4 mg vial 5.1 mL of sterile water for injection into the 20 mg vial using a slow drop -wise addition technique to the inside wall of the vial.

4) Tilt and roll each vial gently. Each vial will yield a 4 mg/mL clear, colorless solution.

5) Visually inspect the reconstituted solution in the vials for particulate matter and discoloration.

Xenpozyme solution should be clear and colorless. Any vials exhibiting opaque particles or discoloration should not be used.

6) Withdraw the volume of reconstituted solution, corresponding to the prescribed dose, from the appropriate number of vials and dilute with sodium chloride 9 mg/mL (0.9%) solution for injection , in a syringe or infusion bag depending on the volume of infusion (see Table 1 for the recommended total infusion volume based on patients age and/or weight) .

Table 1 : Recommended infusion volumes Body weight ≥ 3 kg to < 10 kg Body weight ≥ 10 kg to < 20 kg Body weight ≥ 20 kg (paediatric patients < 18 years) Adult patient s (≥ 18 years) Dose (mg/kg) Total infusion volume (mL) Total infusion volume (mL) Total infusion volume (mL) Total infusion volume (mL) 0.03 Variable volume will vary based on body weight Variable volume will vary based on body weight 5 NA 0.1 Variable volume will vary based on body weight 5 10 20 0.3 5 10 20 100 0.6 10 20 50 100 1.0 20 50 100 100 2.0 50 75 200 100 3.0 50 100 250 100

• For v ariable final volumes of infusion based on body weight in paediatric patients (see Table 1):
• Prepare an infusion solution at 0.1 mg/mL by adding 0.25 mL (1 mg) of the reconstituted solution prepared in step 3) and 9.75 mL of sodium chloride 9 mg/mL ( 0.9% ) solution for injection in an empty 10 mL syringe.
• Calculate the volume (mL) required to obtain the patient dose (mg).

46 Example: 0.3 mg ÷ 0.1 mg/mL = 3 mL

• Dilution instructions for 5 mL ≤ total volume ≤ 20 mL using a syringe:
• Inject the required volume of reconstituted solution slowly to the inside wall of the empty syringe.
• Add slowly the sufficient quantity of sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the syringe).
• Dilution instructions for a total volume ≥ 50 mL using an infusion bag:
• Empty infusion bag: o Inject slowly the required volume of reconstituted solution from step 3) in the appropriate size sterile infusion bag . o Add slowly the sufficient quantity of sodium chloride 9 mg/mL ( 0.9%) solution for injection to obtain the required total infusion volume (avoid foaming within the bag) .
• Pre-filled infusion bag: o Withdraw from the infusion bag pre -filled with sodium chloride 9 mg/mL ( 0.9%) solution for injection the volume of normal saline to obtain a final volume as specified in Table 1. o Add slowly the required volume of the reconstituted solution from step 3) into the infusion bag (avoid foaming within the bag).

7) Gently invert the syringe or the infusion bag to mix. Do not shake. Because this is a protein solution, slight flocculation (described as thin translucent fibers) occurs occasionally after dilution.

8) The diluted solution must be filtered through an in -line low protein -binding 0.2 μm filter during administration.

9) After the infusion is complete, the infusion line should be flushed with sodium chloride 9 mg/mL (0.9%) solution for injection using the same infusion rate as the one used for the last part of the infusion.

📄 Package Leaflet – official source

This article reproduces the information in the official package leaflet, as authorised in the European Union. You can consult the original document here: Product information Xenpozyme (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/22/1659).

⚠️ Important: This article is for information purposes only and does not replace medical advice or the package leaflet inside the medicine box. Read the leaflet carefully before use. For any questions about your treatment, talk to your doctor or pharmacist. If you experience side effects, tell your doctor or pharmacist and report them through your national reporting system.