ELFABRIO 2 mg/ml CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Elfabrio 2 mg/ml concentrate for solution for infusion

pegunigalsidasa alfa

This medicine is subject to additional monitoring, which will allow for quick identification of new safety information. You can help by reporting any side effects you may get. The last section of this leaflet includes information on how to report side effects.

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.

Contents of the pack

1. What is Elfabrio and what is it used for
2. What you need to know before you use Elfabrio
3. How to use Elfabrio
4. Possible side effects
5. Storage of Elfabrio
6. Contents of the pack and other information

1. What is Elfabrio and what is it used for

Elfabrio contains the active substance pegunigalsidasa alfa and is used as enzyme replacement therapy in adult patients with confirmed Fabry disease. Fabry disease is a rare genetic disorder that can affect many parts of the body. In patients with Fabry disease, a fatty substance is not removed from the body's cells and accumulates in the walls of blood vessels, which can cause organ failure. This fatty substance accumulates 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 with confirmed Fabry disease.

2. What you need to know before you use Elfabrio

Do not use Elfabrio

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

Warnings and precautions

Talk to your doctor before starting treatment with Elfabrio.

If you are being treated with Elfabrio, you may experience a side effect during or shortly after administration of the medicine by drip (see section 4). This side effect is called an infusion-related reactionand can sometimes be severe.

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

In very rare cases, your immune system may not be able to recognize Elfabrio and cause a kidney immune disease (membranoproliferative glomerulonephritis). During clinical trials, only one case occurred, and the only symptoms reported were a temporary decrease in kidney function with excess protein in the urine. The symptoms resolved after treatment was stopped.

Children and adolescents

This medicine must not be used in children and adolescents. The safety and efficacy of Elfabrio in children and adolescents from 0 to 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 breastfeeding

You must not receive Elfabrio if you are pregnant, as there is no experience with Elfabrio in pregnant women. If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before receiving this medicine.

It is not known whether Elfabrio is excreted in breast milk. Inform your doctor if you are breastfeeding or plan to breastfeed. Your doctor will help you decide whether to stop breastfeeding or stop treatment with Elfabrio, considering the benefit of breastfeeding to the child and the benefit of Elfabrio to you.

Driving and using machines

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

Elfabrio contains sodium

This medicine contains 46 mg of sodium (main component of cooking/table salt) in each 10 ml vial. This is equivalent to 2% of the maximum daily intake of sodium recommended for an adult.

This medicine contains 11.5 mg of sodium (main component of cooking/table salt) in each 2.5 ml vial. This is equivalent to 1% of the maximum daily intake of sodium recommended for an adult.

3. How to use Elfabrio

This medicine should only be used under the supervision of a doctor with experience in the treatment of Fabry disease or similar diseases and should only be administered by a healthcare professional.

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

You may be told by your doctor that you can be treated at home if you meet certain criteria. Contact your doctor if you wish to be treated at home.

See the information for healthcare professionals at the end of this 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 it («infusion-related reaction», see section 2 «Warnings and precautions»).

While you are being treated with Elfabrio, you may experience some of the following reactions:

Serious side effects

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

• hypersensitivity and severe allergic reaction (symptoms include excessive and prolonged contraction of the muscles of the respiratory tract that causes difficulty breathing [bronchospasm]), swelling of the face, mouth, and throat, wheezing, low blood pressure, hives, difficulty swallowing, skin rash, shortness of breath, flushing, chest discomfort, itching, sneezing, and nasal congestion)

If these side effects occur, seek medical attention immediately and stop the infusion. Your doctor will give you medical treatment if necessary.

Other side effects are

Frequent (may affect up to 1 in 10 people)

• infusion-related reactions
• weakness
• nausea
• skin rash
• abdominal pain
• dizziness
• pain
• chest pain
• headache
• muscle and joint pain
• sensations such as numbness, tingling, or prickling (paresthesia)
• itching (pruritus)
• diarrhea
• vomiting
• chills
• skin redness (erythema)
• feeling that everything is spinning (vertigo), excitement, irritability, or confusion
• abnormal heart rhythm
• agitation

Uncommon (may affect up to 1 in 100 people)

• tremor
• high blood pressure (hypertension)
• bronchospasm (contraction of the bronchial muscles that causes obstruction of the airways) and difficulty breathing
• throat irritation
• body temperature elevation
• difficulty sleeping (insomnia)
• restless legs syndrome
• nerve damage in the arms and legs that causes pain or numbness, burning, and tingling (peripheral neuropathy)
• nerve pain (neuralgia)
• burning sensation
• flushing
• disease in which stomach acid rises to the esophagus (gastroesophageal reflux disease)
• inflammation of the lining (mucosa) of the stomach (dispepsia)
• indigestion
• gas (flatulence)
• decreased sweating (hypohidrosis)
• kidney immune disease that causes excess protein in the urine and kidney dysfunction (membranoproliferative glomerulonephritis)
• chronic kidney disease
• excess protein in the urine (proteinuria)
• tissue damage due to the medicine that is normally infused into a vein escaping or being accidentally infused into the surrounding tissue (extravasation at the infusion site)
• swelling in the lower legs or hands (edema)
• swelling in the arms or legs
• pseudogrippal illness
• nasal congestion and sneezing
• pain at the infusion site
• elevation of liver enzymes and uric acid in the blood, elevation of the protein/creatinine ratio in urine, and presence of leukocytes in the urine in laboratory tests
• weight gain
• low blood pressure (hypotension)
• slow heart rate (bradycardia)
• thickening of the wall inside the heart ventricle

Reporting of side effects

If you experience 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 the Spanish Pharmacovigilance System for Human Use Medicines https://notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of 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 is the last day of the month shown.

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

After dilution, the diluted solution must be used immediately. If not used immediately, the diluted solution must be stored for a maximum of 24 hours in a refrigerator (between 2°C and 8°C) or for a maximum of 8 hours at room temperature (below 25°C).

Do not use this medicine if you notice solid particles or a change in color.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

Composition of Elfabrio

• The active substance is pegunigalsidasa alfa. Each vial contains 20 mg of pegunigalsidasa alfa in 10 ml or 5 mg of pegunigalsidasa alfa in 2.5 ml (2 mg/ml).
• The other ingredients are: sodium citrate tribasic dihydrate, citric acid, and sodium chloride (see section 2 «Elfabrio contains sodium»).

Appearance and pack size

Clear and colorless solution in a transparent glass vial with a rubber stopper and sealed with an aluminum cap.

Pack sizes: 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

You can request more information about this medicine from the local representative of the marketing authorisation holder:

Date of last revision of this leaflet: May 2024

Other sources of information

Detailed information on this medicine 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.

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This information is intended only for healthcare professionals:

Dilution (using an aseptic technique)

1. Determine the total number of vials needed for the infusion.

The number of vials needed is based on the total dose required for each patient and requires calculating a dose based on weight.

An example of calculating the total dose in a patient weighing 80 kg who has been prescribed a dose of 1 mg/kg is as follows:

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

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

Visually inspect the vials. Do not use if the cap is missing or broken. Do not use if there are solid particles or if a color change has occurred.

Avoid shaking or agitating the vials.

1. Withdraw and discard the same volume calculated in step 1 from a sodium chloride 9 mg/ml (0.9%) infusion solution bag.

1. Withdraw the required volume of the Elfabrio solution from the vials and dilute with a sodium chloride 9 mg/ml (0.9%) infusion solution up to the total volume based on the patient's weight as specified in the table below.

Minimum total infusion volume for patients based on body weight

Inject the Elfabrio solution directly into the infusion bag.

DO NOT inject into the air space within the bag.

Gently invert the infusion bag to mix the solution, avoiding vigorous shaking or agitation.

The diluted solution must be administered using a 0.2 μm low-protein-binding in-line filter.