XENPOZYME 20 mg Порошок Для Концентрата Для Инъекционного/Инфузионного Раствора

Содержание инструкции

1. Xenpozyme 4 mg powder for concentrate for solution for infusion, 20 mg powder for concentrate for solution for infusion
   1. What is Xenpozyme and what is it used for
   2. What you need to know before you receive Xenpozyme
   3. How Xenpozyme is administered
   4. Possible side effects
   5. How to store Xenpozyme
   6. Content of the pack and other information

Xenpozyme 4 mg powder for concentrate for solution for infusion, 20 mg powder for concentrate for solution for infusion

olipudase alfa
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before receiving this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or nurse.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or nurse. See section 4.

Contents of this leaflet

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

1. What is Xenpozyme and what is it used for

What is Xenpozyme
Xenpozyme contains an enzyme called olipudase alfa.

What Xenpozyme is used for
Xenpozyme is used to treat a hereditary disorder called acid sphingomyelinase deficiency
(ASMD). It is used in children and adults with ASMD type A/B or type B to treat the signs and symptoms
of ASMD not related to the central nervous system.

How Xenpozyme works
In patients with ASMD, the acid sphingomyelinase enzyme does not function properly. This results in the
accumulation of a substance called sphingomyelin, which damages organs such as the spleen,
liver, heart, lungs, and blood. Olipudase alfa works in the same way as the natural enzyme and
therefore acts as its substitute, reducing the accumulation of sphingomyelin in the organs and treating the
signs and symptoms of the disease.

2. What you need to know before you receive Xenpozyme

You must not receive Xenpozyme

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

Warnings and precautions
You may experience undesirable effects known as infusion-associated reactions which may
be caused by the infusion (intravenous drip) of the medicine. These side effects can occur
during the administration of Xenpozyme or within 24 hours after the infusion.

These can include allergic reactions (see section 4) and symptoms such as headache, itchy skin rash (hives), fever, nausea, vomiting and skin itching.
If you think you are having an infusion-associated reaction, tell your doctor immediately.
If you experience a severe allergic reaction during the infusion, your doctor will stop the infusion and give you
appropriate medical treatment. Your doctor will assess the risks and benefits of
administering further doses of Xenpozyme.
If you experience a mild or moderate infusion-associated reaction, 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 you given) other medicines to prevent or manage
any allergic reactions.
Before starting treatment, your doctor will prescribe blood tests to check the
function of your liver (measuring liver enzyme levels) and, subsequently, at regular
intervals as your doses are adjusted (see section 3).

Other medicines and Xenpozyme
Tell your doctor or nurse if you are taking, have recently taken or might take
any other medicines.

Pregnancy and breastfeeding
If you are pregnant, suspect you may be pregnant or are planning to become pregnant, or if you are
breastfeeding, ask your doctor or nurse for advice before taking this medicine.
There is no experience with the use of Xenpozyme in pregnant women. Xenpozyme, if
taken by a woman during pregnancy, may be harmful to the fetus. Xenpozyme should be
used during pregnancy only when clearly necessary. Women of childbearing potential must
use effective methods of contraception during treatment and, in the event that Xenpozyme is
stopped, for 14 days after the last dose.
It is not known whether Xenpozyme passes into human breast milk. Xenpozyme has been detected in
animal milk. Tell your doctor if you are breastfeeding or intend to do so. Your doctor will then help you
decide whether to stop breastfeeding or to stop taking Xenpozyme,
considering the benefit of breastfeeding for the baby and the benefit of Xenpozyme for the
mother.

Driving and using machines
Xenpozyme may slightly impair the ability to drive and use machines as it can
cause a decrease in blood pressure (which may make you feel dizzy).

Xenpozyme contains sodium
This medicine contains 0.60 mg of sodium (the main component of 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% of the
maximum recommended daily intake of sodium with the diet for an adult
or adolescent, and ≤ 0.08% and ≤ 0.38% of the maximum acceptable daily intake of sodium for children
under 16 years of age, respectively.

3. How Xenpozyme is administered

Xenpozyme is administered via an intravenous infusion (infusion) under the supervision of a healthcare professional experienced in the treatment of ASMD or other metabolic diseases.
The recommended dose to receive is based on body weight and is administered every two weeks.
Treatment begins with a low dose of the medicine, which is gradually increased.
The infusion usually lasts from 3 to 4 hours approximately, but may be shorter or longer depending on the
doctor's judgment; furthermore, it may be shorter during the period in which the dose is increased.
Adult patients
The recommended initial dose of Xenpozyme is 0.1 mg per kg of body weight. This is
increased in a scheduled manner with each subsequent administration, up to reaching the recommended dose of 3 mg per kg of body weight, every 2 weeks. Typically, up to
14 weeks are needed to reach the recommended dose, but it may take longer depending on the doctor's judgment.
Children
The recommended initial dose of Xenpozyme is 0.03 mg per kg of body weight. Subsequent doses should be increased in a scheduled manner to reach the recommended
dose of 3 mg per kg of body weight every 2 weeks. Typically, up to 16 weeks are needed
to reach the recommended dose, but it may take longer, depending on the doctor's judgment.
Home infusion
If a stable dose is taken and a good level of tolerance to Xenpozyme infusions is achieved, the doctor may consider home infusion. The decision to
switch to home infusion must be made after evaluation and recommendation by the
doctor. If, during a Xenpozyme infusion, you experience a side effect, the person administering the home infusion may stop the infusion and initiate appropriate medical
treatment.
Instructions for correct use
Xenpozyme is administered through intravenous infusion (intravenous drip). It is supplied
in the form of a powder that must be mixed with sterile water before administration.

If you are given more Xenpozyme than you should
Immediately inform your doctor if you suspect a change compared to the usual infusion.

If you miss a Xenpozyme infusion
It is important to receive the infusion every 2 weeks. An infusion is considered missed if it is not
administered within 3 days of the scheduled administration. Depending on the number of doses
missed, your doctor may need to restart administration from a lower dose.
If you have missed an infusion or are unable to attend a scheduled appointment, contact your
doctor immediately.
If you have any questions about 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 everyone will experience them.
Cases of infusion-related reactions have been observed while patients were receiving the
medicine or within 24 hours after the infusion.
The most serious side effects can include severe and sudden allergic reactions, itchy rash (hives), skin
rash, increased liver enzymes, and irregular heartbeat.
You should immediately inform your doctor if you experience an infusion-related reaction or an
allergic reaction.
If you experience an infusion reaction, you may be given other medicines to treat or
help prevent future reactions. If the infusion reaction is severe, your doctor may
interrupt the Xenpozyme infusion and initiate appropriate medical treatment.

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

• headache
• fever
• itchy skin rash (hives)
• nausea
• vomiting
• abdominal pain (stomach)
• muscle pain
• skin itching
• increased values in blood tests indicating inflammation
• Common (may affect up to 1 in 10 people):
• skin rash (different types of rash sometimes with tingling)
• pain in the upper abdomen
• fatigue
• abnormal blood tests for liver function
• diarrhoea
• skin redness
• joint pain
• back pain
• chills
• difficulty breathing
• abdominal discomfort
• bone pain
• pain
• low blood pressure
• forceful heartbeat that may be fast or irregular
• fast heartbeat
• liver pain
• severe allergic reactions
• feeling of intense heat
• irritation of the throat and vocal cords
• tightness and swelling of the throat
• wheezing
• skin lesions (such as raised or flat red bumps)
• rapid swelling under the skin in areas such as the face, throat, arms, and legs, which can be life-threatening if swelling of the throat obstructs the airways
• stomach pain
• itchy or red eyes
• eye discomfort
• weakness
• abnormal blood tests indicating inflammation
• reactions related to the catheter site, including pain, tingling, or swelling

Reporting of side effects
If you get any side effect, talk to your doctor or nurse. You can also report side effects directly through
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 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 on the packaging. The expiry date refers to the last day of that month.
Store in a refrigerator (2 °C – 8 °C).
After dilution, it is recommended to use the solution immediately.
If not used immediately, the reconstituted solution can be stored for a maximum of
24 hours at a temperature between 2 °C and 8 °C or up to 12 hours at room temperature (up to
25 °C).
After dilution, the solution can be stored for a maximum of 24 hours at 2 °C – 8 °C.
Do not dispose of any medicine in wastewater or household waste. Ask your doctor or
nurse how to dispose of medicines you no longer use. This will help protect
the environment.

6. Content 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.
• The other ingredients are:
• L-methionine
• dibasic sodium phosphate heptahydrate
• monobasic sodium phosphate monohydrate
• sucrose See section 2 Xenpozyme contains sodium.

Description of the appearance of Xenpozyme and contents of the pack
Xenpozyme is a powder for concentrate for solution for infusion in a vial (4 or
20 mg/vial).
It is a lyophilized powder from white to off-white.
After mixing with sterile water, a clear and colorless solution is obtained. The solution
must be further diluted before infusion.

Marketing Authorisation 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 medicine, 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 republikaMagyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
Sanofi A/S
Tlf: +45 45 16 70 00
sanofi-aventis, s.r.o.
Tel: +420 233 086 111

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

Norge
sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 16 00

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Österreich
sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España
sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
sanofi-aventis 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 hf.
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

United Kingdom (Northern Ireland)
sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +44 (0) 800 035 2525

Other sources of information
More detailed information on this medicine is available on the website of the European
Medicines Agency http://www.ema.europa.eu . Also, other links to rare diseases
and their therapeutic treatments are reported on the web.

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 below (and on the outer packaging) with a smartphone.

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The following information is intended exclusively for healthcare professionals:
Preparation of the solution for administration
The powder for concentrate for solution for infusion must be reconstituted with water for
injections, diluted with sodium chloride 9 mg/mL (0.9%) solution for injection and then
administered via intravenous infusion.
The reconstitution and dilution steps must be carried out under aseptic conditions. During the
preparation of the infusion solution, never use filtering devices. During the reconstitution and
dilution steps, avoid foam formation.

• 1) Based on the individual patient's weight and the prescribed dose, determine the number of vials to reconstitute. Patient weight (kg) x dose (mg/kg) = patient dose (in mg). For example, if using a 20 mL vial: 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 allow them to reach room temperature for about 20-30 minutes.
• 3) Reconstitute each vial by injecting: ‐ 1.1 mL of water for injections into the 4 mg vial ‐ 5.1 mL of water for injections into the 20 mg vial using a slow addition technique, drop by drop, against the inner wall of the vial.
• 4) Gently tilt and rotate each vial. Each vial will produce a clear and colorless solution at 4 mg/mL.
• 5) Visually inspect the reconstituted solution inside the vials for the presence of particulate matter and discoloration. The Xenpozyme solution must be clear and colorless. Do not use vials that show opaque particles or discoloration.
• 6) Withdraw the volume of reconstituted solution corresponding to the prescribed dose from the appropriate number of vials and dilute with a 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 age and/or patient weight).

Table 1 – Recommended infusion volumes

• In pediatric patients, for varying final infusion volumes, based on body weight (see Table 1):
• in an empty 10 mL syringe, prepare an infusion solution at 0.1 mg/ mL, 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
• calculate the volume (mL) needed to obtain the patient dose (mg). Example: 0.3 mg ÷ 0.1 mg/mL = 3 mL
• Instructions for dilution for a total volume between ≥5 mL and ≤20 mL, using a syringe: ‐ slowly inject the required volume of reconstituted solution against the inner wall of the empty syringe ‐ slowly add sufficient sodium chloride 9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid foam formation inside the syringe).
• Instructions for dilution for a total volume ≥50 mL, using an infusion bag:

empty infusion bag:
or inject slowly into the sterile infusion bag, of appropriate size, the
required volume of reconstituted solution in step 3)
or slowly add the sufficient amount of sodium chloride
9 mg/mL (0.9%) solution for injection to obtain the required total infusion volume (avoid
foam formation inside the bag)
pre-filled infusion bag:
or withdraw from the pre-filled infusion bag with sodium chloride
9 mg/mL (0.9%) solution for injection the volume of normal saline solution to obtain a
final volume as specified in Table 1
or slowly add into the infusion bag the required volume of the
reconstituted solution in step 3) (avoid foam formation inside the bag).

• 7) To mix, gently invert the syringe or infusion bag. Do not shake. Being a protein solution, slight flocculation (described as fine translucent fibers) occasionally occurs after dilution.
• 8) During administration, the diluted solution must be filtered through an in-line low protein binding filter, 0.2 μm.

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

APPENDIX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION

Scientific conclusions
Taking into account the assessment by the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Reports (PSUR) for olipudase alfa, the scientific
conclusions of the PRAC are as follows:
Based on available data from clinical and medical sources, on reactions, some serious, associated with infusion, including four cases of overdose in children caused by errors related to
dose escalation and, given a plausible mechanism of action, the PRAC concluded that the product information of products containing olipudase alfa must be amended accordingly.
After reviewing the PRAC recommendation, the CHMP agrees with the PRAC’s overall conclusions
and the reasons for the recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on olipudase alfa, the CHMP considers that the benefit/risk
ratio of the medicinal product containing olipudase alfa is unchanged, subject to the proposed changes
to the medicine information.
The CHMP recommends the variation of the terms of the marketing authorisation.