REPLAGAL 1 mg /Ml Concentrate For Infusion Solution

Зміст інструкції

1. Replagal 1 mg/ml concentrate for solution for infusion
   1. What is Replagal and what is it used for
   2. What you need to know before you receive Replagal
   3. How Replagal is administered
   4. Possible side effects
   5. How to store Replagal
   6. Contents of the pack and other information

Replagal 1 mg/ml concentrate for solution for infusion

agalsidase alfa

Read this leaflet carefully before you start this medicine because 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet

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

1. What is Replagal and what is it used for

The active substance of Replagal is agalsidase alfa (1 mg/ml). Agalsidase alfa is a form of the human α-galactosidase enzyme produced by activating the gene for α-galactosidase A at the cellular level. The enzyme is then extracted from the cells and transformed into a sterile concentrate for infusion solution.
Replagal is used in the treatment of adult, adolescent and children patients aged over 7 years with a confirmed diagnosis of Fabry disease. It is administered as long-term enzyme replacement therapy when enzyme levels in the body are absent or below normal, as in the case of Fabry disease.
After 6 months of therapy, a significant reduction in pain was observed in patients treated with Replagal compared to patients treated with placebo (dummy drug). Replagal reduced the mass of the left ventricle compared to placebo. These results indicate an improvement in disease symptoms or disease stabilization.

2. What you need to know before you receive Replagal

Do not receive Replagal

• if you are allergic to agalsidase alfa or any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor or pharmacist before using Replagal.
If you notice any of the following symptoms during or after an infusion, you should immediately inform your
doctor:

• high fever, chills, sweating, rapid heartbeat;
• vomiting.
• feeling of dizziness.
• hives.
• swelling of the hands, feet, ankles, face, lips, mouth or throat, causing difficulty swallowing or breathing.

Your doctor may decide to temporarily interrupt the infusion (5-10 minutes), to
resume it after the symptoms have disappeared.
The doctor may also treat the symptoms with other medicines (antihistamines or corticosteroids).
In most cases you will be able to continue to receive Replagal despite the appearance of these
symptoms.
In case of a severe allergic reaction (of the anaphylactic type), the administration of Replagal will be
immediately stopped and the doctor will have to start appropriate therapy.
It is possible that treatment with Replagal may cause your body to produce antibodies, which
however will not prevent the medicine from working and may disappear over time.
In case of advanced stage kidney disease, the effect of treatment with Replagal on your kidneys may
be limited. Talk to your doctor or pharmacist before using Replagal.

Children
Experience in children aged 0 to 6 years is limited, therefore no dosage regimen can be recommended
for this age group.

Other medicines and Replagal
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
Tell your doctor if you are using medicines containing chloroquine, amiodarone, benoquin or gentamicin. There is
a theoretical risk of a reduction in agalsidase alfa activity.

Pregnancy and breastfeeding
Very limited clinical data on pregnancies exposed to Replagal have not shown any adverse effects on
the mother and the newborn.
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding with
breast milk, ask your doctor or pharmacist for advice before taking this medicine.

Driving and using machines
During therapy with Replagal, you will be able to drive and use machines.

Replagal contains sodium
This medicine contains 14.2 mg of sodium (the main component of table salt) per each
vial. This is equivalent to 0.7% of the maximum recommended daily intake with the diet
of an adult.

Registrations
In order to improve the traceability of biological medicines, healthcare professionals are required to record
clearly the name and batch number of the product administered. Ask your doctor for
any questions.

3. How Replagal is administered

This medicine must be administered by and under the supervision of specially trained personnel, who will also calculate the necessary dose. While remaining under the doctor's supervision, Replagal can be self-administered (by you or the person assisting you) after adequate training by the attending doctor and/or nurse. Self-administration must take place in the presence of a responsible adult.
The recommended dose is an infusion of 0.2 mg per each kg of body weight, corresponding to approximately 14 mg or 4 vials (glass bottles) of Replagal for an individual of normal constitution (70 kg).

Use in children and adolescents
In children and adolescents between 7 and 18 years of age, a dose of 0.2 mg/kg can be used every other week.
Children and adolescents may develop infusion reactions more likely than adults. Inform your doctor of the onset of any undesirable effects during the infusion.

Method of administration
Before use, Replagal must be diluted with a 0.9% sodium chloride solution (9 mg/ml).
After dilution, Replagal will be injected into a vein, generally in the arm.
The infusion is performed every two weeks.
Each time, the intravenous administration of Replagal will last at least 40 minutes. The infusion will be performed under the control of a doctor specialized in the treatment of Fabry disease.
For self-administration, the established dose and infusion rate must not be modified without the consent of the attending doctor.

If you use more Replagal than you should
If you believe you have used more Replagal than you should have, contact your doctor.

If you use less Replagal than you should
If you believe you have used less Replagal than you should have, contact your doctor.

If you forget to use Replagal
If you have missed an infusion of Replagal, contact your doctor.

If you stop taking Replagal
Do not stop treatment with Replagal without contacting your doctor. If you have any doubts about the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you develop a severe allergic reaction (of an anaphylactic type), the administration of Replagal will be
immediately stopped and your doctor will institute appropriate therapy.
Most side effects are mild to moderate in intensity. More than 1 in 10 people (frequency “very common”)
may develop adverse reactions during or after the infusion of Replagal (infusion-related reactions), including
chills, headache, nausea, fever, fatigue, restlessness, difficulty breathing, tremor, cough and vomiting.
However, some of these effects may be severe and require subsequent treatment. In patients with Fabry
disease affecting the cardiac structures, infusion-related reactions with cardiac effects, including myocardial
ischemia and heart failure may occur (frequency “not known” (the frequency cannot be estimated from
available data)). The doctor may temporarily interrupt the infusion (5-10 minutes) until the symptoms
disappear and then resume it. The doctor may also treat the symptoms with other medicines (antihistamines
or corticosteroids). In most cases you will be able to continue to take Replagal despite these symptoms.
Other side effects
Very common: may affect more than 1 in 10 people

• swelling of tissues (e.g. legs, arm)
• tingling or numbness or pain in the fingers of the hands or feet
• ringing in the ear
• palpitations
• sore throat
• abdominal pain, diarrhea
• skin rash
• back pain or limb pain, muscle pain, joint pain
• chest pain, cold symptoms, fever, feeling unwell

Common: may affect up to 1 in 10 people

• taste alteration, prolonged sleep
• tearing
• increased ringing in the ear
• increased heart rate, heart rhythm disorders
• increased blood pressure, decreased blood pressure, flushing (redness)
• hoarseness or throat tightness, runny nose
• abdominal discomfort
• acne, reddened, itchy or mottled skin, excessive sweating
• muscle and bone discomfort, swelling of the extremities or joints
• hypersensitivity
• chest tightness, increased feeling of lack of energy, feeling of cold or hot, flu-like symptoms, discomfort

Uncommon: may affect up to 1 in 100 people

• severe allergic reaction (of an anaphylactic type)
• abnormal eyelid reflex
• increased heart rate
• low blood oxygen level and viscous secretions of the throat
• altered smell
• the accumulation of fluid under the skin can lead to swelling of body parts, marbled discoloration of the skin e.g. of the leg
• feeling of heaviness
• skin rash at the injection site Children and adolescents

The side effects observed in children have generally been similar to those of adults.
However, children have more frequently experienced infusion-related reactions (fever,
difficulty breathing, chest pain) and more intense pain.

Reporting of side effects
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not
listed in this leaflet. You can also report side effects directly through 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 Replagal

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 and on the package after
Exp. The expiry date refers to the last day of that month.
Store in a refrigerator (2  C – 8  C).
Do not use Replagal if you notice the presence of foreign particles or a change in color.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Replagal contains

• The active substance is agalsidase alfa. Each ml of Replagal contains 1 mg of agalsidase alfa.
• The other ingredients are: sodium phosphate monobasic monohydrate polysorbate 20 sodium chloride sodium hydroxide water for injections

Replagal contains sodium. See section 2.

Description of the appearance of Replagal and contents of the pack
Replagal is a concentrate for solution for infusion in vials containing 3.5 mg/3.5 ml of
agalsidase alfa. Packs of 1, 4 or 10 vials are available. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50–58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland

Manufacturer
Takeda Pharmaceuticals International AG Ireland Branch
Block 2 Miesian Plaza
50–58 Baggot Street Lower
Dublin 2
D02 HW68
Ireland
Shire Pharmaceuticals Ireland Limited
Block 2 & 3 Miesian Plaza
50–58 Baggot Street Lower
Dublin 2
Ireland
For further information on this medicinal product, contact the local representative of the Marketing
Authorisation Holder:

België/Belgique/Belgien
Takeda Belgium NV
Tel/Tél: +32 2 464 06 11
[email protected]

Lietuva
Takeda, UAB
Tel: +370 521 09 070
[email protected]

България
Такеда България ЕООД
Тел.: +359 2 958 27 36
[email protected]

Luxembourg/Luxemburg
Takeda Belgium NV
Tel/Tél: +32 2 464 06 11
[email protected]

Česká republika
Takeda Pharmaceuticals Czech Republic s.r.o.
Tel: +420 234 722 722
[email protected]

Magyarország
Takeda Pharma Kft.
Tel: +36 1 270 7030
[email protected]

Danmark
Takeda Pharma A/S
Tlf: +45 46 77 10 10
[email protected]

Malta
Τakeda HELLAS S.A.
Tel: +30 210 6387800
[email protected]

Deutschland
Takeda GmbH
Tel: +49 (0)800 825 3325
[email protected]

Nederland
Takeda Nederland B.V.
Tel: +31 20 203 5492
[email protected]

Eesti
Takeda Pharma AS
Tel: +372 6177 669
[email protected]

Norge
Takeda AS
Tlf: +47 800 800 30
[email protected]

Ελλάδα
Τakeda ΕΛΛΑΣ Α.Ε.
Τηλ: +30 210 6387800
[email protected]

Österreich
Takeda Pharma Ges.m.b.H.
Tel: +43 (0) 800-20 80 50
[email protected]

España
Takeda Farmacéutica España S.A
Tel: +34 917 90 42 22
[email protected]

Polska
Takeda Pharma Sp. z o.o.
Tel: +48223062447
[email protected]

France
Takeda France SAS
Tél. + 33 1 40 67 33 00
[email protected]

Portugal
Takeda Farmacêuticos Portugal, Lda.
Tel: + 351 21 120 1457
[email protected]

Hrvatska
Takeda Pharmaceuticals Croatia d.o.o.
Tel: +385 1 377 88 96
[email protected]

România
Takeda Pharmaceuticals SRL
Tel: +40 21 335 03 91
[email protected]

Ireland
Takeda Products Ireland Ltd
Tel: 1800 937 970
[email protected]

Slovenija
Takeda Pharmaceuticals farmacevtska družba d.o.o.
Tel: + 386 (0) 59 082 480
[email protected]

Ísland
Vistor hf.
Sími: +354 535 7000
[email protected]

Slovenská republika
Takeda Pharmaceuticals Slovakia s.r.o.
Tel: +421 (2) 20 602 600
[email protected]

Italia
Takeda Italia S.p.A.
Tel: +39 06 502601
[email protected]

Suomi/Finland
Takeda Oy
Puh/Tel: 0800 774 051
[email protected]

Κύπρος
Τakeda ΕΛΛΑΣ Α.Ε.
Τηλ: +30 210 6387800
[email protected]

Sverige
Takeda Pharma AB
Tel: 020 795 079
[email protected]

Latvija
Takeda Latvia SIA
Tel: +371 67840082
[email protected]

United Kingdom (Northern Ireland)
Takeda UK Ltd
Tel: +44 (0) 2830 640 902
[email protected]

Other sources of information
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 physicians and healthcare professionals:

Instructions for use, handling and disposal
Replagal must be administered under the supervision of a physician specialising in the treatment of
Fabry disease or other inherited metabolic disorders.
Replagal is administered every other week at a dose of 0.2 mg/kg body weight by
intravenous infusion over 40 minutes.

• 1. Calculate the dose and the number of vials of Replagal required.
• 2. Dilute the total volume of Replagal concentrate required in 100 ml of 0.9% sodium chloride solution for intravenous use (9 mg/ml). Because Replagal does not contain preservatives or bacteriostatic agents, utmost care must be taken to maintain the sterility of the solution: this requires working under aseptic conditions. Once diluted, the solution should be gently swirled without shaking.
• 3. Before administration, the solution must be visually inspected for the presence of particulate matter or discoloration.
• 4. Administer the solution over an interval of 40 minutes, using an intravenous infusion set with an integrated filter. Because the solution does not contain preservatives, it is recommended to administer it as soon as possible. From a physicochemical point of view, however, the diluted solution is stable for 24 hours at 25 °C.
• 5. Do not administer Replagal in the same infusion set with other medicinal products.
• 6. The solution is for single use. Unused product and waste materials derived from this medicinal product must be disposed of in accordance with local legal requirements.