XENPOZYME 20 mg POWDER FOR CONCENTRATE FOR INFUSION SOLUTION

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

Xenpozyme must not be given to you:

• If you have had potentially life-threatening allergic reactions (anaphylactic reactions) to olipudase alfa (see section “Warnings and precautions” below) or to 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 can be caused by the infusion (drip) of the medicine. These can occur while you are being given Xenpozyme or in the 24 hours after the infusion.

These can include allergic reactions (see section 4) and symptoms such as headache, raised and itchy rash (hives), fever, nausea, vomiting, and itchy skin.

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

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

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

Your doctor may also give you (or have given you) other medicines to prevent or control allergic reactions.

Your doctor will ask for blood tests to check how your liver is working (by measuring your liver enzyme levels) before starting 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 breastfeeding

If you are pregnant or breastfeeding, 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 harm the fetus if taken by a pregnant woman. Xenpozyme should only be used during pregnancy if it is clearly necessary. Women who can become pregnant must use effective contraception during treatment and for 14 days after the last dose if Xenpozyme is interrupted.

It is not known whether Xenpozyme passes into human breast milk. Xenpozyme was detected in animal milk. If you are breastfeeding or plan to breastfeed, tell your doctor. Your doctor will then help you decide whether you must stop breastfeeding or stop Xenpozyme, considering the benefit of breastfeeding to the child and the benefit of Xenpozyme to the mother.

Driving and using machines

Xenpozyme may have a minor influence on your ability to drive and use machines, as you may experience a drop in blood pressure (which can make you feel dizzy).

Xenpozyme contains sodium

This medicine contains 0.60 mg of sodium (a major component of cooking/table salt) per 4 mg vial or 3.02 mg of sodium per 20 mg vial. This is equivalent to 0.03% and 0.15%, respectively, of the maximum recommended 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 16 years of age.

3. How Xenpozyme is given

Xenpozyme will be given to you as an infusion (drip) under the supervision of a healthcare professional with experience in the treatment of ASMD or other metabolic disorders.

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

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

The infusion usually lasts around 3 to 4 hours, but can be shorter or longer depending on your doctor’s decision, and 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 kg of body weight. This is increased in a planned manner with each subsequent dose, up to the recommended dose of 3 mg per kg of body weight every 2 weeks. It usually takes up to 14 weeks to reach the recommended dose, but this time may be longer depending on your doctor’s decision.

Children

The recommended initial dose of Xenpozyme is 0.03 mg per kg of body weight. Subsequent doses should be increased in a planned manner up to the recommended dose of 3 mg per kg of body weight every 2 weeks. It usually takes up to 16 weeks to reach the recommended dose, but this time may be longer depending on your doctor’s decision.

Home infusion

Your doctor may consider infusing Xenpozyme at home if you are on a stable dose and are tolerating your infusions well. The decision to switch to home infusion should be made after evaluation and recommendation by your doctor. If you have a side effect during a Xenpozyme infusion, the person administering your infusion at home can stop the infusion and start the appropriate medical treatment.

Instructions for proper use

Xenpozyme is given by infusion into a vein. It is supplied as a powder that will be mixed with sterile water before administration.

If you are given too much Xenpozyme

Tell your doctor immediately if you suspect a change in your usual infusion.

If you miss an infusion of Xenpozyme

It is important that you receive your infusion every 2 weeks. You are considered to have missed an infusion if it is not given within 3 days after the scheduled infusion. Depending on the number of missed doses, your doctor may need to start again from a lower dose.

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

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 in patients while they were receiving the medicine or in the 24 hours after the infusion.

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

You should tell your doctor immediately if you experience 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 Xenpozyme infusion and start the appropriate medical treatment.

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

• Headache
• Raised and itchy rash (hives)
• Fever - elevated body temperature Nausea
• Abdominal pain (stomach)
• Vomiting
• Itchy skin
• Muscle pain
• Rash
• Abnormal blood tests due to inflammation
• Pain in the upper stomach
• Redness of the skin

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

• Red or itchy eyes

• Joint pain
• Fatigue
• Abnormal blood tests due to liver function
• Diarrhea
• Low blood pressure
• Difficulty breathing
• Abdominal discomfort
• Rash (different types of rash sometimes with itching)
• Back pain
• Pain
• Chills

• Feeling too hot

• Wheezing (difficulty breathing) Irritation of the throat and larynx
• Liver pain
• Skin lesions (such as solid raised or flat red patches)
• Bone pain
• Weakness
• Severe allergic reactions
• Eye discomfort
• Fast heartbeats
• Strong and fast or irregular heartbeats
• Throat and larynx constriction and swelling, 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
• Reactions at the infusion site, including pain, itching, or swelling
• Abnormal blood tests due to 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. Storage of Xenpozyme

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

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

Store in a refrigerator (2°C - 8°C).

After reconstitution, it is recommended to use immediately.

If not used immediately, the reconstituted solution can be stored for up to 24 hours in a refrigerator (2°C - 8°C).

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

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

6. Container Contents and Additional Information

Xenpozyme Composition

The active ingredient is olipudasa alfa. One vial contains 4 mg or 20 mg of olipudasa alfa.

The other components are:

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

See section 2 Xenpozyme contains sodium

Product Appearance and Container Contents

Xenpozyme is a 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 with sterile water, it is a clear and colorless solution. The solution should be further diluted before infusion.

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 Leaflet:

Other Sources of Information

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.

This leaflet can be found in all languages of the European Union/European Economic Area on the European Medicines Agency website and on the website: www.xenpozyme.info.sanofi, or by scanning the QR code included below (also included on 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 powder for concentrate for solution for infusion should be reconstituted with sterile water for injection, diluted with sodium chloride 9 mg/ml (0.9%) injection solution, and then administered by intravenous infusion.

The reconstitution and dilution steps should be completed under aseptic conditions. Filters should not 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 individual patient's weight and prescribed dose.

Patient weight (kg) x 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.

1. Remove the required number of vials from the refrigerator and wait for approximately 20 to 30 minutes to allow them to reach room temperature.
2. 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-by-drop technique on the inner wall of the vial.

1. Gently tilt and rotate each vial. Each vial should result in a clear and colorless solution of 4 mg/ml.
2. Visually inspect the reconstituted solution in the vials for particles or discoloration. The Xenpozyme solution should be clear and colorless. Do not use any vial that shows opaque particles or discoloration.
3. 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%) injection solution 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 final infusion volumes based on body weight in pediatric 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%) injection solution in an empty 10 ml syringe.
• Calculate the volume (ml) needed to achieve the patient dose (mg).

Example: 0.3 mg ÷ 0.1 mg/ml = 3 ml

• Dilution instructions for 5 ml ≤ total volume ≤ 20 ml using a syringe:

• Slowly inject the required volume of the reconstituted solution into the empty syringe.
• Slowly add sufficient sodium chloride 9 mg/ml (0.9%) injection solution to achieve the required total infusion volume (avoid foam formation within the syringe).

• Dilution instructions for total volume ≥ 50 ml using an infusion bag:

• Empty infusion bag:
• Slowly inject the required volume of the reconstituted solution from step 3) into the sterile infusion bag of appropriate size.
• Slowly add sufficient sodium chloride 9 mg/ml (0.9%) injection solution to achieve the required total infusion volume (avoid foam formation within the bag).

• Pre-filled infusion bag:
• Withdraw from the pre-filled infusion bag with sodium chloride 9 mg/ml (0.9%) injection solution the volume of normal saline solution to achieve a final volume as specified in Table 1.
• Slowly add the required volume of the reconstituted solution from step 3) into the infusion bag (avoid foam formation within the bag).

1. Gently invert the syringe or infusion bag to mix. Do not shake. As this is a protein solution, occasional slight flocculation (described as thin translucent fibers) may occur after dilution.
2. The diluted solution should be filtered through a 0.2 μm low-protein-binding filter in-line during administration.

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