InfoCons Consumer Protection informs you – Elfabrio – Package Leaflet

Before anything else

Read all of this leaflet carefully before you start using 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 pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

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

Elfabrio contains the active substance pegunigalsidase al fa, and is used as enzyme replacement therapy in adult patients with confirmed Fabry disease. Fabry disease is a rare genetic disease that can affect many parts of the body. In p atients with Fabry disease, a fat substance is not removed from the cells of their body, and builds up in the walls of blood vessels which can cause organ failure. This f at builds up in the cells of these patients because they do not have enough of an enzyme called α- galactosidase-A, the enzyme responsible for breaking it down Elfabrio is used long -term to supplement or replace this enzyme in adult patients who have confirmed Fabry disease.

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

Do not use Elfabrio

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

Warnings and precautions

Talk to your doctor before Elfabrio is used.

If you are treated with Elfabrio, you may experience a side effect during or immediately following the drip (infusion) used to give the medicine (see section 4). This is known as an infusion- related reaction and can sometimes be severe.

• Infusion- related reactions include dizziness, headache, nausea, low blood pressure, tiredness and fever. If you experience an infusion- related reaction, you must tell your doctor immediately .
• If you have an infusion-related reaction you may be given additional medicines to treat or help prevent future reactions. These medicines may include medicines used to treat allergies 25 (antihistamines), medicines used to treat fever (antipyretics) and medicines to control inflammation (corticosteroids).
• If the infusion -related reaction is severe, your doctor will stop the infusion immediately and start giving you appropriate medical treatment or slow down treatment rate.
• If the infusion -related reactions are severe and/or there is a loss of effect from this medicine, your doctor will perform a blood test to check for antibodies that might affect the outcome of your treatment.
• Most of the time you can still be given Elfabrio even if you experience an infusion- related reaction.

In very rare cases, your immune system may not be able to recognise Elfabrio , leading to an immunological kidney disease ( membranoproliferative glomerulonephritis ). During the clinical studies, only one case occurred , and the only sy mptoms reported were a temporary decline of renal functions with excess protein s in the urine . The symptoms resolved upon discontinuation of the treatment .

Treatment monitoring For patients switched to Elfabrio 2 mg/kg body weight once every 4 weeks, regular monitoring (e.g.: after 3, 6, 12, 18 and 24 months) should be performed . Monitoring should include at least the evaluation of lyso -Gb3, renal ( eGFR, proteinuria), cardiac (LVMi, NT -proBNP, troponin or ECG), and biochemical parameters . A change in any individual parameter should be interpreted in the context of the patient’s overall clinical status, and clinically relevant deterioration should prompt re -evaluation of the treatment regimen.

Children and adolescents

This medicine should not be used in children and adolescents. The safety and efficacy of Elfabrio in children and adolescents aged 0 -17 years have not been established.

Other medicines and Elfabrio

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

Pregnancy and breast -feeding You should not use Elfabrio if you are pregnant , since t here is no experience with Elfabrio in pregnant women . If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor for advice before you are given this medicine.

It is unknown whether Elfabrio is excreted in human 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 stop taking Elfabrio, considering the benefit of breast-feeding for your baby and the benefit of Elfabrio for you.

Driving and using machines

Elfabrio may cause dizziness or vertigo. If you feel dizzy or vertigo or experience syncope on the day of treatment with Elfabrio, do not to drive or use machines until you feel better.

Elfabrio contains sodium

This medicine contains 46 mg sodium (main component of cooking/table salt) in each 10 mL vial.

This is equivalent to 2 % of the recommended maximum daily dietary intake of sodium for an adult.

This medicine contains 11.5 mg sodium (main component of cooking/table salt) in each 2.5 mL vial.

This is equivalent to 1% of the recommended maximum daily dietary intake of sodium for an adult.

💊 3. How Elfabrio is given

This medicine is only to be used under the supervision of a doctor experienced in the treatment of Fabry disease or other similar diseases and should only be given by a healthcare professional.

The recommended dose is 1 mg/kg of body weight given once every two weeks.

The treatment can be also administered at the dose of 2 mg/kg of body weight every four weeks in patients stable with an ERT treatment.

Your doctor may advise that you can be treated at home provided you meet certain criteria. Please contact your doctor if you would like to be treated at home.

Special populations Hepatic impairment No dose adjustment is needed in patients with hepatic impairment.

Renal impairment No dose adjustment is needed in patients with renal impairment. Renal function should be evaluated regularly during Elfabrio treatment.

The presence of extensive renal damage (eGFR < 60 ml/min) may limit the renal response to enzyme replacement therapy, possibly due to underlying irreversible pathological changes. In such cases, the loss of renal function remains within the expected range of the natural progression of disease. Regular evaluation of changes in the estimated glomerular filtration rate (eGFR) during Elfabrio treatment is recommended.

See information for h ealth care p rofessionals at the end of this package leaflet.

❗ 4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. Most side effects occur during the infusion or shortly after (“infusion- related reaction”, see section 2 “Warnings and precautions” ).

While under treatment with Elfabrio, you may experience some of the following reactions:

Serious side effects

Common side effects (may affect up to 1 in 10 people)

• hypersensitivity and serious allergic reaction (symptoms including excessive and prolonged contraction of the airway muscles causing breathing difficulty (bronchospasm), swelling of the face, mouth and throat, wheezing, low blood pressure, hives, difficulty swallowing, rash, shortness of breath, flushing, chest discomfort , itchiness, nausea, chills, sneezing and nasal congestion) If these side effects happen, immediately seek medical attention and stop the infusion. Your doctor will give you medical treatment if required .

Other side effects include

Common (may affect up to 1 in 10 people)

• infusion related reactions
• weakness
• feeling sick (nausea)
• rash
• abdominal pain
• dizziness
• pain
• chest pain 27 • headache
• muscle and joint pain
• sensations like numbness, tingling, or pins and needles (paraesthesia)
• itching (pruritus)
• diarrh oea
• vomiting
• chills
• redding of the skin (erythema)
• a spinning sensation (v ertigo ), arousa l, irritability or confusion
• alteration of the normal heart rhythm
• agitation

Uncommon ( may affect up to 1 in 100 people)

• shaking (tremor)
• high blood pressure (hypertension)
• bronchospasm (contraction of the bronchial muscles causing obstruction of breathing airways) and difficult breathing
• throat irritation
• throat tightness
• increased body temperature
• difficulty sleeping (insomnia)
• restless legs syndrome
• nerve damage in arms and legs causing pain or numbness, burning and tingling (peripheral neuropathy)
• nerve pain (neuralgia)
• burning sensation
• syncope
• flushing
• disease where stomach acid goes upwards into the oesophagus (gastro -oesophageal reflux disease)
• inflammation of the stomach lining (dyspepsia)
• indigestion
• gas (flatulence)
• diminished sweating (hypohydrosis)
• immunological kidney disease causing excess protein in the urine and renal malfunctioning (membranoproliferative glomerulonephritis)
• chronic kidney disease
• excess protein in the urine (proteinuria)
• tissue damage because the medicine that is normally infused into a vein leaks or is accidentally infused into the surrounding tissue (infusion site extravasation)
• swelling of lower legs or hands (oedema)
• swelling of arms or legs
• influenza- like illness
• nasal congestion and sneezing
• infusion site pain
• increased uric acid in the blood, increased urine protein/creatinine ratio, white blood cells in the urine, as tested in the laboratory
• weight increase
• low blood pressure (hypotension)

Reporting of side effects

If you get any side effects, talk to your doctor. This includes any possible side effects not listed in this leaflet. You can also report side effects d irectly 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 Elfabrio

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 carton after “ EXP ”. The expiry date refers to the last day of that month.

Store in a refrigerator (2 °C-8 °C) .

After dilution, the diluted solution should be used immediately. If not used immediately, the diluted solution should be stored for no longer than 24 hours in a refrigerator (2 °C-8 °C) or for no longer than 8 hours at room temperature (below 25 °C ).

Do not use this medicine if you notice particles or discolouration.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist 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 Elfabrio contains

• The active substance is pegunigalsidase alfa. Each vial contains 20 mg pegunigalsidase alfa in 10 mL or 5 mg pegunigalsidase alfa in 2 .5 mL (2 mg/mL )
• The other ingredients are: tribasic dihydrate s odium citrate , citric acid , and sodium chloride (see

section 2 “Elfabrio contains sodium ”).

What Elfabrio looks like and contents of the pack

Clear and colourless solution in clear glass vial with a rubber stopper and sealed with aluminium flip off cap.

Pack size s: 1, 5 or 10 vials.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Chiesi Farmaceutici S.p.A.

Via Palermo 26/A 43122 Parma Italy

Manufacturer

Chiesi Farmaceutici S.p.A.

Via San Leonardo 96 43122 Parma Italy For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Chiesi sa/nv Tél/Tel: + 32 (0)2 788 42 00 Lietuva Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 29 България ExCEEd Orphan Distribution d.o.o.

Тел.: +359 87 663 1858 Luxembourg/Luxemburg Chiesi sa/nv Tél/Tel: + 32 (0)2 788 42 00 Česká republika Chiesi CZ s.r.o. Tel: + 420 261221745 Magyarország ExCEEd Orphan Distribution d.o.o.

Tel.: +36 70 612 7768 Danmark Chiesi Pharma AB Tlf: + 46 8 753 35 20 Malta Chiesi Farmaceutici S.p.A.

Tel: + 39 0521 2791 Deutschland Chiesi GmbH Tel: + 49 40 89724-0 Nederland Chiesi Pharmaceuticals B.V.

Tel: + 31 88 501 64 00 Eesti Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 Norge Chiesi Pharma AB Tlf: + 46 8 753 35 20 Ελλάδα Chiesi Hellas AEBE Τηλ: + 30 210 6179763 Österreich Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 España Chiesi España, S.A.U. Tel: + 34 934948000 Polska ExCEEd Orphan Distribution d.o.o. Tel.: +48 799 090 131 France Chiesi S.A.S.

Tél: + 33 1 47688899 Portugal Chiesi Farmaceutici S.p.A.

Tel: + 39 0521 2791 Hrvatska Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 România Chiesi Romania S.R.L.

Tel: + 40 212023642 Ireland Chiesi Farmaceutici S.p.A.

Tel: + 39 0521 2791 Slovenija CHIESI SLOVENIJA, d.o.o.

Tel: + 386-1-43 00 901 Ísland Chiesi Pharma AB Sími: +46 8 753 35 20 Slovenská republika Chiesi Slovakia s.r.o. Tel: + 421 259300060 Italia Chiesi Italia S.p.A.

Tel: + 39 0521 2791 Suomi/Finland Chiesi Pharma AB Puh/Tel: +46 8 753 35 20 Κύπρος Chiesi Farmaceutici S.p.A.

Τηλ: + 39 0521 2791 Sverige Chiesi Pharma AB Tel: +46 8 753 35 20 Latvija Chiesi Pharmaceuticals GmbH Tel: + 43 1 4073919 30 This leaflet was last revised in Other sources of information Detailed information on this medicine is available on the European Medicines Agency web site: https://www.ema.europa.eu . There are also links to other websites about rare diseases and treatments. ————————————————————————————————————————

🩺 Information intended for healthcare professionals only

Dilution (using a septic technique) 1) Determine the total number of vials required for the infusion.

The number of vials required is based on the total dose required for each individual patient and requires calculation for weight-based dosing.

An example calculation for total dose in an 80 kg patient prescribed 1 mg/kg is as follows:

• Patient weight (in kg) ÷ 2 = Volume of dose (in mL)
• Example: 80 kg patient ÷ 2 = 40 mL (volume to be withdrawn).
• In this example, 4 vials of the 10 mL vial (or 16 vials of the 2.5 mL vial) are needed.

An example calculation for total dose in an 80 kg patient prescribed 2 mg/kg is as follows:

• Patient weight (in kg) = Volume of dose (in mL)
• Example: 80 kg patient = 80 mL (volume to be withdrawn).
• In this example, 8 vials of the 10 mL vial (or 32 vials of the 2.5 mL vial) are needed.

2) Allow the required number of vials to reach room temperature prior to dilution (approximately 30 minutes).

Visually inspect the vials. Do not use if cap is missing or broken. Do not use if there is particulate matter or if it is discoloured.

Avoid shaking or agitating the vials.

3) Remove and discard the same volume as calculated in step 1 of sodium chloride 9 mg/mL (0.9%) solution for infusion from the infusion bag.

4) Withdraw the required volume of Elfabrio solution from the vials, and dilute with sodium chloride 9 mg/mL (0.9%) solution for infusion, to a total volume based on patient weight specified in the t able below.

Minimum total infusion volume for patients by body weight Patient weight Minimum total infusion volume < 70 kg 150 mL 70–100 kg 250 mL > 100 kg 500 mL Inject the Elfabrio solution directly into the infusion bag.

Do NOT inject in the airspace within the infusion bag. Gently invert the infusion bag to mix the solution, avoiding vigorous shaking and agitation.

The diluted solution should be administered using an inline low protein binding 0.2 μm filter.

📄 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 Elfabrio (PDF, ec.europa.eu).

You can check this medicine at any time in the Union Register of medicinal products (EU number EU/1/23/1724).

⚠️ 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.