Xenpozyme 4 mg polvo para concentrado para solucion para perfusion

Product Information for the Patient

Xenpozyme 4mg Powder for Concentrate for Solution for Infusion

Xenpozyme 20mg Powder for Concentrate for Solution for Infusion

olipudasa alfa

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

Read this entire product information carefully before starting to use this medication, as it contains important information for you.

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

What is Xenpozyme

Xenpozyme contains an enzyme called olipudase alfa.

What is Xenpozyme used for

Xenpozyme is used to treat a hereditary disorder called acid sphingomyelinase deficiency (ASMD). It is used in children and adults with ASMD of 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 functioning version of the acid sphingomyelinase enzyme. This causes the accumulation of a substance called sphingomyelin, which damages organs such as the spleen, liver, heart, lungs, and blood. The olipudase alfa acts in the same way as the natural enzyme, so it acts as a substitute, reducing the accumulation of sphingomyelin in the organs and treating the signs and symptoms.

You should not be administered Xenpozyme:

• If you have experienced potentially fatal allergic reactions to olipudase alfa (see the "Warnings and precautions" section below) or to any of the other components of this medication (listed in section 6).

Warnings and precautions

You may have adverse effects called infusion-associated reactions (IARs) that may be caused by the infusion (drip) of the medication. They may occur while you are being administeredXenpozymeor within 24 hours after the infusion.

They may include allergic reactions (see section 4) andsymptoms such as headache, raised itchy hives, fever, nausea, vomiting, and skin itching.

If you think you are having an IAR,inform your doctor immediately.

If you have a severe allergic reaction during the infusion, your doctor will stop the infusion and provide you with the necessary medical treatment.Your doctor will decide on the risks and benefits of administering more doses of Xenpozyme.

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

Your doctor may also administer (or have administered) other medications to prevent or control allergic reactions.

Your doctor will request blood tests to check how your liver is functioning (by measuring your liver enzyme levels) before starting treatment and, subsequently, at regular intervals as you adjust the doses (see section 3).

Other medications and Xenpozyme

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or nurse before using this medication.

There is no experience with the use of Xenpozyme in pregnant women. Xenpozyme may be harmful to the fetus if a woman takes it during pregnancy. Xenpozyme should only be used during pregnancy if it is clearly necessary. Women who may become pregnant should use effective birth control methods during treatment and for 14 days after the last dose if treatment is interruptedXenpozyme.

It is unknown whether Xenpozyme passes into human breast milk. Xenpozyme was detected in animal milk. Inform your doctor if you are breastfeeding or plan to do so. Your doctor will help you decide whetherit is necessary to stop breastfeeding orthe administration of Xenpozyme, after consideringthe benefit of breastfeeding for the baby and the benefitof Xenpozymefor the mother.

Driving and operating machinery

Xenpozyme may have a mild effect on your ability to drive and operate machinery, as you may experience a drop in blood pressure (which can make you feel dizzy).

Xenpozyme contains sodium

This medication contains 0.60 mg of sodium (main component of table salt/for cooking) per 4 mg vial or 3.02mg of sodium per 20 mg vial. This corresponds to 0.03% and 0.15%, respectively, of the recommended maximum daily sodium intake for an adult or adolescent, and<0.08 % and<0.38 %, respectively, of the maximum acceptable daily sodium intake for children under 16years of age.

Xenpozyme will be administered as an infusion (perfusion) under the supervision of a healthcare professional experienced in the treatment of ASMD or other metabolic disorders.

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

The treatment starts with a low dose of the medication, which is gradually increased.

The infusion typically lasts around 3 to 4 hours; however, it may be shorter or longer at the discretion of your doctor, and it may be shorter during the period when your dose is being increased..

Adult patients

The recommended initial dose of Xenpozyme is 0.1 mg per kilogram of body weight. This is increased in a planned manner with each subsequent dose, until the recommended dose of 3 mg per kilogram of body weight is reached every two weeks. It usually takes up to 14 weeks to reach the recommended dose, but this time may be longer at the discretion of your doctor.

Children

The recommended initial dose of Xenpozyme is 0.03 mg per kilogram of body weight. Subsequent doses should be increased in a planned manner until the recommended dose of 3 mg per kilogram of body weight is reached every two weeks. It usually takes up to 16 weeks to reach the recommended dose, but this time may be longer at the discretion of your doctor.

Home infusion

Your doctor may consider infusing Xenpozyme at home if you are receiving a stable dose and tolerate your infusions well. The decision to switch to home infusion should be made after evaluation and recommendation by your doctor. If you experience an adverse effect during a Xenpozyme infusion, the person administering your infusion at home may interrupt the infusion and initiate appropriate medical treatment.

Instructions for proper use

Xenpozyme is administered by intravenous infusion (a drip in a vein). It is supplied as a powder that will be mixed with sterile water before administration.

If you receive more Xenpozyme than you should

Inform your doctor immediately if you suspect a change from your usual infusion.

If a Xenpozyme infusion is missed

It is essential to receive the infusion every two weeks. A missed infusion is considered to be any infusion not administered within three days of the scheduled infusion. Depending on the number of missed doses, your doctor may need to restart from a lower dose.

If you have missed an infusion or cannot attend a scheduled appointment, contact your doctor immediately.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

Reactions associated with infusion (RAPs) have been observed while patients were receiving the medicine or within 24 hours after the infusion.

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

You must inform your doctor immediately if you experiencea RAP or an allergic reaction.

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

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

• Headache
• Fever - elevated body temperature
• Raised and itchy hives
• Nausea
• Vomiting
• Abdominal pain (stomach)
• Muscle pain
• Itching skin
• Blood test with elevated values due to inflammation

Common (may affect up to 1 in 10 people):

• Rash (different types of rash sometimes with itching)
• Upper abdominal pain
• Fatigue
• Abnormal blood test due to liver function
• Diarrhea
• Skin redness
• Joint pain
• Back pain
• Chills
• Difficulty breathing
• Abdominal discomfort
• Bone pain
• Pain
• Low blood pressure
• Strong heartbeats that may be rapid or irregular
• Rapid heartbeats
• Liver pain
• Severe allergic reactions
• Sensation of extreme heat
• Irritation of the throat and larynx
• Throat constriction and swelling
• Wheezing (difficulty breathing)
• Skin lesions (such as solid raised or flat red lesions)
• Rapid swelling under the skin in areas such as the face, throat, arms, and legs, which can be life-threatening if the throat swelling blocks the airways
• Stomach pain
• Red or itchy eyes
• Eye discomfort
• Weakness
• Abnormal blood test due to inflammation
• Reactions related to the catheter site, which include pain, itching, or swelling

Reporting of side effects

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

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

Do not use Xenpozyme after the expiration date that appears on the label and packaging. The expiration date is the last day of the month indicated.

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

After dilution, it is recommended to use immediately.

If not used immediately, the reconstituted solution can be stored for up to 24 hours at a temperature between 2°C and 8°C.

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

Medicines should not be disposed of through drains or in the trash. Ask your doctor or nurse how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Xenpozyme Composition

The active ingredient is olipudase alfa. A vial contains 4 mg or 20 mg of olipudase alfa.

The other components are:

• L-methionine
• Sodium phosphate heptahydrate
• Sodium phosphate monobasic monohydrate
• Sucrose

see section 2 Xenpozyme contains sodium

Appearance of the product and contents of the container

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

The powder is a white to off-white lyophilized powder.

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

Marketing Authorization Holder

Sanofi B.V., Paasheuvelweg 25, 1105 BP Amsterdam, Netherlands

Responsible for manufacturing

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

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet:

Other sources of information

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

This leaflet is available in all languages of the European Union/European Economic Area on the website of the European Medicines Agency and on the website:www.xenpozyme.info.sanofi,or by scanning the QR code included below (also included in the outer packaging) with a smartphone.

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This information is intended for healthcare professionals only:

Preparation of the solution for administration

The lyophilized powder for concentrate for solution for infusion must be reconstituted with sterile water for injection to prepare the solution for infusion.

The reconstituted solution must be further diluted with sodium chloride 9 mg/ml (0.9%) solution for injection before administration.

The reconstitution and dilution steps must be completed in aseptic conditions. No filtration devices should be used at any time during the preparation of the infusion solution. Avoid foam formation during the reconstitution and dilution steps.

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

Patient weight (kg) × dose (mg/kg) = patient dose (in mg). For example, when using vials of 20 mg, 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 the refrigerator and wait for approximately 20-30 minutes to allow them to reach room temperature.

3) Reconstitute each vial by injecting:

1.1 ml of sterile water for injection into the vial of 4 mg

5.1 ml of sterile water for injection into the vial of 20 mg

using a slow addition technique to the inner wall of the vial.

4) Incline and rotate each vial gently. Each vial should yield a clear and colorless solution of 4 mg/ml.

5) Visually inspect the reconstituted solution in the vials to check for particles or discoloration. The Xenpozyme solution should be clear and colorless. Any vial showing opaque particles or discoloration should not be used.

6) Extract the volume of reconstituted solution corresponding to the prescribed dose from the required 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 infusion volume (see Table 1 for the recommended total infusion volume based on patient age and/or weight).

Table 1: Recommended infusion volumes

• For variable infusion volumes based on patient weight in pediatric patients (see Table 1):

• Prepare a solution for infusion 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 a 10 ml empty syringe.
• Calculate the volume (ml) needed to obtain the patient's dose (mg).

Example: 0.3 mg ÷ 0.1 mg/ml = 3 ml

• Instructions for dilution for 5 ml ≤ total volume ≤ 20 ml using a syringe:

• Inject the required volume of the reconstituted solution slowly into the inner wall of the empty syringe.
• Add the required amount of sodium chloride 9 mg/ml (0.9%) solution for injection slowly to obtain the total infusion volume needed (avoid foam formation within the syringe).

• Instructions for dilution for a total volume ≥ 50 ml using an infusion bag:

• Empty infusion bag:
• Inject the required volume of the reconstituted solution from step 3) slowly into the empty infusion bag.
• Add the required amount of sodium chloride 9 mg/ml (0.9%) solution for injection slowly to obtain the total infusion volume needed (avoid foam formation within the bag).

• Preloaded infusion bag:
• Extract the required volume of sodium chloride 9 mg/ml (0.9%) solution for injection from the preloaded infusion bag to obtain the total infusion volume specified in Table 1.
• Add the required volume of the reconstituted solution from step 3) slowly to the infusion bag (avoid foam formation within the bag).

7) Invert the syringe or infusion bag gently to mix. Do not agitate. Due to the protein nature of the solution, occasional slight flocculation (described as thin translucent fibers) may occur after dilution.

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

9) Once the infusion is complete, the infusion site must be flushed with sodium chloride 9 mg/ml (0.9%) solution for injection at the same infusion rate used in the last part of the infusion.