EPYSQLI 300 MG CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Epysqli 300 mg concentrate for solution for infusion

eculizumab

This medicine is subject to additional monitoring, which will help to quickly identify 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, pharmacist, or nurse.
• 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, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Epysqli and what is it used for

What is Epysqli

The active substance of Epysqli is eculizumab and belongs to a group of medicines called monoclonal antibodies. Eculizumab binds to a specific protein in the body that causes inflammation and inhibits it, so that the body's systems cannot attack and destroy vulnerable blood cells, kidneys, muscles, or nerves of the eyes and spinal cord.

What Epysqli is used for

Paroxysmal Nocturnal Hemoglobinuria

Epysqli is used to treat adult and child patients with a specific type of disease that affects the blood system called paroxysmal nocturnal hemoglobinuria (PNH). In patients with PNH, red blood cells can be destroyed, which can cause a reduction in the number of red blood cells (anemia), fatigue, functional impairment, pain, darkening of the urine, difficulty breathing, and blood clots. Eculizumab can block the body's inflammatory response and its ability to attack and destroy its own vulnerable blood cells.

Atypical Hemolytic Uremic Syndrome

Epysqli is also used to treat adult and child patients with a certain type of disease that affects the blood system and kidneys called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, their kidneys and blood cells, including platelets, can be damaged, which can lead to low blood cell counts (thrombocytopenia and anemia), decreased or lost kidney function, blood clots, fatigue, and difficulty functioning normally. Eculizumab can block the body's inflammatory response and its ability to attack and destroy its own vulnerable blood cells and kidneys.

2. What you need to know before you use Epysqli

Do not use Epysqli

• If you are allergic to eculizumab, to mouse-derived products, to other monoclonal antibodies, or to any of the other ingredients of this medicine (listed in section 6).
• If you have not been vaccinated against meningococcal infection, unless you take antibiotic treatment to reduce the risk of infection until 2 weeks after being vaccinated.
• If you have a meningococcal infection.

Warnings and precautions

Meningococcal infection and other Neisseria infections alert

Treatment with Epysqli may reduce your natural resistance to infections, especially to certain organisms that cause meningococcal infection (a serious infection of the brain lining and sepsis) and other Neisseria infections, including disseminated gonorrhea.

Consult your doctor before using Epysqli to ensure that you are vaccinated against Neisseria meningitidis, one of the microorganisms that cause meningococcal infection, at least 2 weeks before starting treatment or that you receive antibiotic treatment to reduce the risk of infection until 2 weeks after being vaccinated. Make sure you are up to date with your meningococcal vaccinations. Also, keep in mind that vaccination does not always prevent these types of infections. According to national recommendations, your doctor may consider it necessary to apply additional measures to prevent infection.

If you are at risk of gonorrhea, ask your doctor or pharmacist for information before starting this medicine.

Symptoms of meningococcal infection

Given the importance of rapid identification and treatment of certain infections in patients treated with Epysqli, you will be given a card with a list of specific symptoms of infections to carry with you at all times. It is called the "Patient Safety Card".

If you experience any of the following symptoms, inform your doctor immediately:

• headache with nausea or vomiting
• headache with stiffness of the neck or back
• fever
• rash
• confusion
• severe muscle pain combined with flu-like symptoms
• sensitivity to light

Treatment of meningococcal infection during travel

If you plan to travel to a remote area where you will not be able to contact your doctor or receive medical treatment for some time, your doctor may take preventive measures, such as prescribing an antibiotic against Neisseria meningitidis for you to carry with you. If you experience any of the above symptoms, you should take the prescribed antibiotic. Remember that you must see a doctor as soon as possible, even if you feel better after taking the antibiotic.

Infections

Before using Epysqli, inform your doctor if you have any infection.

Allergic reactions

Epysqli contains a protein and proteins can cause allergic reactions in some people.

Children and adolescents

Patients under 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal infections.

Elderly

No special precautions are required for the treatment of patients aged 65 years and over.

Other medicines and Epysqli

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Women of childbearing potential

In women of childbearing potential, the use of effective contraceptive methods should be considered during treatment and for up to 5 months after treatment.

Pregnancy/breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines

Epysqli has no or negligible influence on the ability to drive and use machines.

Epysqli contains sodium

Once diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.47 g of sodium (main component of cooking/table salt) in 240 ml at the maximum dose. This is equivalent to 23.4% of the maximum recommended daily intake of sodium for an adult. You should be aware of this if you are on a low-sodium diet.

Once diluted with sodium chloride 4.5 mg/ml (0.45%) solution for injection, this medicine contains 0.26 g of sodium (main component of cooking/table salt) in 240 ml at the maximum dose. This is equivalent to 12.8% of the maximum recommended daily intake of sodium for an adult. You should be aware of this if you are on a low-sodium diet.

Epysqli contains polysorbate 80

This medicine contains 6.6 mg of polysorbate 80 in each vial (30 ml vial), equivalent to 0.66 mg/kg or less of the maximum dose for adult patients and pediatric patients with a body weight over 10 kg, and equivalent to 1.32 mg/kg or less of the maximum dose for pediatric patients with a body weight of 5 to <10 kg. polysorbates can cause allergic reactions. inform your doctor if you or child have any known allergy.< p>

3. How to use Epysqli

At least 2 weeks before starting treatment with Epysqli, your doctor will administer a vaccine against meningococcal infection if you have not been previously vaccinated or if the vaccine you received has expired. If your child is under the age required for vaccination or if you have not been vaccinated at least 2 weeks before starting treatment with Epysqli, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after being vaccinated.

Your doctor will administer a vaccine to your child under 18 years of age against Haemophilus influenzae and pneumococcal infections according to local vaccination recommendations for each age group.

Instructions for proper use

Your doctor or another healthcare professional will administer the treatment, which consists of the infusion of a diluted vial of Epysqli prepared in a drip bag, through a tube directly into a vein. The initial phase of treatment, or initial phase, is recommended to last 4 weeks, after which the maintenance phase will begin:

If you are using this medicine to treat PNH

For adults:

• Initial phase:

During the first four weeks, your doctor will administer an intravenous infusion of Epysqli diluted every week. Each infusion will consist of a dose of 600 mg (2 vials of 30 ml) and will last 25 to 45 minutes (35 minutes ± 10 minutes).

• Maintenance phase:

• In the fifth week, your doctor will administer an intravenous infusion of Epysqli diluted corresponding to a dose of 900 mg (3 vials of 30 ml) for 25-45 minutes (35 minutes ± 10 minutes).
• After the fifth week, your doctor will administer 900 mg of Epysqli diluted every two weeks as long-term treatment.

If you are using this medicine to treat aHUS

For adults:

• Initial phase:

During the first four weeks, your doctor will administer an intravenous infusion of Epysqli diluted every week. Each administration will consist of a dose of 900 mg (3 vials of 30 ml) and will last 25 to 45 minutes (35 minutes ± 10 minutes).

• Maintenance phase:

• In the fifth week, your doctor will administer an intravenous infusion of Epysqli diluted corresponding to a dose of 1200 mg (4 vials of 30 ml) for 25-45 minutes (35 minutes ± 10 minutes).
• After the fifth week, your doctor will administer 1200 mg of Epysqli diluted every two weeks as long-term treatment.

For children and adolescents

Children and adolescents with PNH or aHUS with a weight of 40 kg or more will be treated with the adult dose.

Children and adolescents with PNH or aHUS with a weight of less than 40 kg require a lower dose based on their weight. Your doctor will calculate it.

In the case of children and adolescents with PNH or aHUS under 18 years of age:

After each infusion, you should remain under observation for one hour and follow your doctor's instructions to the letter.

If you have received more Epysqli than you should

If you suspect that you have accidentally been given a higher dose of Epysqli than prescribed, consult your doctor.

If you miss an appointment to receive Epysqli

If you miss an appointment, consult your doctor immediately and read the section "If you stop treatment with Epysqli".

If you stop treatment with Epysqli in PNH

If you stop or discontinue treatment with Epysqli, it is possible that PNH symptoms may recur more intensely immediately after stopping treatment. Your doctor will discuss the possible side effects and explain the risks. Additionally, your doctor will closely monitor you for at least 8 weeks.

The risks of stopping treatment with Epysqli include an increase in the destruction of your red blood cells, which can cause:

• a significant decrease in the number of red blood cells (anemia);
• confusion or lack of attention;
• chest pain or angina;
• increased serum creatinine concentration (kidney problems); or
• thrombosis (blood clots).

If you experience any of these symptoms, contact your doctor.

If you stop treatment with Epysqli in aHUS

If you stop or discontinue treatment with Epysqli, it is possible that aHUS symptoms may recur. Your doctor will discuss the possible side effects and explain the risks. Additionally, your doctor will closely monitor you.

The risks of stopping treatment with Epysqli include an increase in the inflammatory processes of your platelets, which can cause:

• a significant decrease in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of your red blood cells;
• decreased urination (kidney problems);
• increased serum creatinine concentration (kidney problems);
• confusion or lack of attention;
• chest pain or angina;
• shortness of breath; or
• thrombosis (blood clots).

If you experience any of these symptoms, contact your doctor.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Your doctor will discuss the possible adverse effects and explain the risks and benefits of Epysqli before starting treatment.

The most serious adverse effect was meningococcal sepsis (frequency not known [cannot be estimated from available data]).

If you experience any symptoms of meningococcal infection (see section 2 "Meningococcal Infection and Other Neisseria Infections Alert"), inform your doctor immediately.

If you are not sure what the adverse effects listed below are, ask your doctor to explain them.

Very Common(may affect more than 1 in 10 patients):

• headache.

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

• pulmonary infection (pneumonia), cold (nasopharyngitis), urinary tract infection (urinary infection);
• low white blood cell count (leucopenia), reduction of red blood cells that can cause paleness and weakness or shortness of breath;
• insomnia;
• dizziness, high blood pressure;
• upper respiratory tract infection, cough, sore throat (oropharyngeal pain), bronchitis, fever (herpes simplex);
• diarrhea, vomiting, nausea, abdominal pain, rash, hair loss (alopecia), itching (pruritus);
• joint pain (arms and legs), pain in the limbs (arms and legs);
• fever (pyrexia), feeling of fatigue (fatigue), flu-like illness;
• infusion-related reaction.

Uncommon(may affect up to 1 in 100 patients):

• severe infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, gastrointestinal flu (gastrointestinal infection), cystitis;
• infections, fungal infection, pus accumulation (abscesses), skin infection (cellulitis), flu, sinusitis, dental infection (abscess), gum infection;
• relatively low platelet count (thrombocytopenia), low level of lymphocytes (a specific type of white blood cell) (lymphopenia), feeling of palpitations;
• severe allergic reactions causing difficulty breathing or dizziness (anaphylactic reaction), hypersensitivity;
• loss of appetite;
• depression, anxiety, mood changes, sleep disorder;
• tingling sensation in a part of the body (paresthesia), tremor, taste disorder (dysgeusia), fainting;
• blurred vision;
• ringing in the ears, dizziness;
• sudden and rapid development of extremely high blood pressure, low blood pressure, hot flashes, venous disorders;
• shortness of breath (dyspnea), nosebleed, stuffy nose (nasal congestion), throat irritation, nasal discharge (rhinorrhea);
• peritoneal inflammation (tissue that lines most abdominal organs), constipation, stomach upset after eating (dyspepsia), abdominal distension;
• hives, skin redness, skin dryness, red or purple spots on the skin, increased sweating, skin inflammation;
• muscle cramp, muscle pain, back and neck pain, bone pain;
• kidney disorders, difficulty or pain when urinating (dysuria), blood in urine;
• spontaneous erection;
• swelling (edema), chest discomfort, feeling of weakness (asthenia), chest pain, pain at the infusion site, chills;
• increased liver enzymes, decreased proportion of blood volume occupied by red blood cells, decreased protein that carries oxygen in red blood cells;

Rare(may affect up to 1 in 1000 patients):

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus infection, impetigo, bacterial sexually transmitted disease (gonorrhea);
• skin tumor (melanoma), bone marrow disorder;
• red blood cell destruction (hemolysis), cellular aggregation, abnormal coagulation factor, abnormal coagulation;
• disease with hyperthyroidism (Graves' disease);
• abnormal dreams;
• eye irritation;
• bruises;
• unusual gastric reflux of food, gum pain;
• yellowing of the skin and/or eyes (jaundice);
• skin color disorders;
• muscle spasms in the mouth, joint swelling;
• menstrual disorder;
• abnormal release of the medicine from the infused vein, abnormal sensation at the infusion site, feeling of heat.

Adverse Effect Reporting

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Epysqli

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

Do not use this medicine after the expiration date that appears on the box and the label of the vial after "CAD". The expiration date is the last day of the month indicated.

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

Do not freeze.

Epysqli vials can be stored in the original packaging outside the refrigerator for a single period of up to 2 months at room temperature (up to 30 °C), without exceeding the original expiration date. At the end of this period, the product can be returned to the refrigerator.

Store in the original packaging to protect it from light.

After dilution, the medicine must be used within 24 hours at between 2 °C and 8 °C or at room temperature (up to 30 °C). However, if the solution is prepared under aseptic conditions (sterile), it can be stored in the refrigerator at between 2 °C and 8 °C for up to 3 months and for 72 hours more at room temperature (up to 30 °C) when diluted with sodium chloride 9 mg/ml (0.9%) injectable solution, sodium chloride 4.5 mg/ml (0.45%) injectable solution.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Epysqli

• The active ingredient is eculizumab (300 mg/30 ml in a vial corresponding to 10 mg/ml).
• The other components are:

• sodium dihydrogen phosphate monohydrate (see section 2 "Epysqli contains sodium")
• disodium hydrogen phosphate heptahydrate (see section 2 "Epysqli contains sodium")
• trehalose dihydrate
• polysorbate 80

Solvent: water for injectable preparations

• Epysqli contains sodium and polysorbate 80. See section 2.

Appearance of the Product and Package Contents

Epysqli is presented as a concentrate for solution for infusion (30 ml in a vial – package size of 1 vial).

Epysqli is a clear and colorless solution.

Marketing Authorization Holder and Manufacturer

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

Date of the Last Revision of this Leaflet:

Other Sources of Information

Detailed information about this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu and on the Spanish Agency for Medicines and Health Products (AEMPS) website (http://www.aemps.gob.es/). There are also links to other websites about rare diseases and orphan medicines.

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Instructions for Healthcare Professionals

Handling of Epysqli

This information is intended only for healthcare professionals.

1- How is Epysqli Supplied?

Each vial of Epysqli contains 300 mg of active ingredient in 30 ml of product solution.

2- Before Administering the Medicine

Reconstitution and dilution must be performed in accordance with good practice standards, especially with regard to asepsis.

Epysqli must be prepared using an aseptic technique for subsequent administration by a qualified healthcare professional.

• Visually inspect the Epysqli solution to ensure it does not contain particles or color changes.
• Withdraw the necessary amount of Epysqli from the vial or vials using a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute Epysqli to a final concentration of 5 mg/ml (initial concentration divided by 2) by adding the appropriate amount of diluent to the infusion bag. To prepare a dose of 300 mg, use 30 ml of Epysqli (10 mg/ml) and add 30 ml of solvent. For a dose of 600 mg, use 60 ml of Epysqli and add 60 ml of diluent. For a dose of 900 mg, use 90 ml of Epysqli and add 90 ml of diluent. For 1200 mg, use 120 ml of Epysqli and add 120 ml of diluent. The final volume of a diluted Epysqli solution of 5 mg/ml is 60 ml for doses of 300 mg, 120 ml for doses of 600 mg, 180 ml for doses of 900 mg, or 240 ml for doses of 1200 mg.
• The diluents that can be used are sodium chloride 9 mg/ml (0.9%) injectable solution, sodium chloride 4.5 mg/ml (0.45%) injectable solution, or 5% glucose solution in water.
• Gently shake the infusion bag with the diluted Epysqli solution to ensure the medicine and diluent are well mixed.
• Allow the diluted solution to warm to room temperature (up to 30 °C) before administration, by exposure to ambient air.
• The diluted solution must not be heated in a microwave or any other heat source other than room temperature.
• Discard any remaining medicine in the vial.
• The diluted Epysqli solution can be stored between 2 °C and 8 °C or at room temperature (up to 30 °C) for 24 hours once removed from the refrigerator. However, if the solution is prepared under aseptic conditions (sterile), it can be stored in the refrigerator at between 2 °C and 8 °C for up to 3 months and for 72 hours more at room temperature (up to 30 °C) when diluted with sodium chloride 9 mg/ml (0.9%) injectable solution, sodium chloride 4.5 mg/ml (0.45%) injectable solution.

3- Administration

• Do not administer Epysqli by direct intravenous injection or by bolus injection.
• Epysqli should only be administered by intravenous infusion.
• The diluted Epysqli solution should be administered by intravenous infusion over 25 to 45 minutes (35 minutes ± 10 minutes) in adults and 1-4 hours in pediatric patients under 18 years of age by gravity drip, a syringe pump, or an infusion pump. It is not necessary to protect the Epysqli diluted solution from light during administration to the patient.

The patient should be monitored for one hour after infusion. If an adverse effect occurs during the administration of Epysqli, the infusion can be interrupted or the rate reduced, according to the doctor's judgment. If the rate is reduced, the total duration of the infusion should not exceed two hours in adults and no more than 4 hours in pediatric patients under 18 years of age.

4- Special Storage and Handling Conditions

Store in a refrigerator (between 2 °C and 8 °C). Do not freeze. Store in the original packaging to protect it from light. Epysqli vials can be stored in the original packaging outside the refrigerator for a single period of up to 2 months at room temperature (up to 30 °C), without exceeding the original expiration date. At the end of this period, the product can be returned to the refrigerator.

Do not use this medicine after the expiration date that appears on the box and the label of the vial after "CAD". The expiration date is the last day of the month indicated.