Prospect: information for the user

Epysqli 300 mg concentrate for infusion solution

eculizumab

This medicine is subject to additional monitoring, which will expedite the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribed only to you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

What is Epysqli

The active ingredient of Epysqli is eculizumab and it belongs to a group of medications 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 eye nerves and spinal cord.

What is Epysqli used for

Paroxysmal nocturnal hemoglobinuria

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

Atypical hemolytic uremic syndrome

Epysqli is also used for the treatment of adult and pediatric patients with a certain type of circulatory and renal disease called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, their kidneys and blood cells, including platelets, may be damaged, leading to low blood counts (thrombocytopenia and anemia), decreased or lost renal 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 and renal cells.

No use Epysqli

• If you are allergic to eculizumab, to proteins derived from mouse products, have had an allergic reaction to other monoclonal antibodies or to any of the other components of this medication (listed in section 6).
• If you have not been vaccinated against meningococcal infection, unless you have received 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 alert and other infections byNeisseria

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

Consult your doctor before using Epysqli to ensure that you are vaccinated againstNeisseria meningitidis, one of the microorganisms that produces meningococcal infection, at least 2 weeksbefore 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 on your meningococcal vaccinations. Also, note that vaccination does not always prevent infections of this type. In accordance with national recommendations, your doctor may consider it necessary to apply additional measures to prevent infection.

If you are at risk of developing gonorrhea, ask your doctor or pharmacist for information before starting to use this medication.

Symptoms of meningococcal infection

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

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

• Bothersome headache accompanied by nausea or vomiting
• Bothersome headache accompanied by neck or back stiffness
• Fever
• Rash
• Confusion
• Intense 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 the necessary preventive measures, such as prescribing an antibiotic againstNeisseria meningitidisfor you to carry with you. If you experience any of the symptoms mentioned above, you must take the prescribed antibiotic. Remember that you must see your 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 infections.

Allergic reactions

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

Children and adolescents

Patients under 18 years old must be vaccinated againstHaemophilus influenzaeand pneumococcal infections.

Older adults

No special precautions are necessary for the treatment of patients aged 65 years and older.

Other medications and Epysqli

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Women of childbearing age

Women of childbearing age should consider using effective contraceptive methods during treatment and for 5 months after treatment.

Pregnancy/breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medication.

Driving and operating machinery

The influence of Epysqli on the ability to drive and operate machinery is negligible or insignificant.

Epysqli contains sodium

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

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

At least 2 weeks before starting treatment with Epysqli, your doctor will administer a vaccine against meningococcal infection if you have not been vaccinated previously or if the vaccine administered to you has expired. If your child is under the required age 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 old againstHaemophilus influenzaeand pneumococcal infections in accordance with local vaccination recommendations for each age range.

Instructions for proper use

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

If you use this medication to treat HPN

For adults:

• Initial phase:

During the first 4 weeks, your doctor will administer an intravenous infusion of Epysqli diluted every week. Each administration 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 5th 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 5th week, your doctor will administer 900 mg of Epysqli diluted every 2 weeks as long-term treatment.

If you use this medication to treat SHUa

For adults:

• Initial phase:

During the first 4 weeks, your doctor will administer an intravenous infusion ofEpysqlidiluted every week. Each administration will consist of a dose of up to 900mg (3vials of 30ml) and will last 25 to 45minutes (35minutes±10minutes).

• Maintenance phase:
• • In the 5th week, your doctor will administer an intravenous infusion ofEpysqlidiluted corresponding to a dose of up to 1200mg (4vials of 30ml) for 25-45 minutes (35 minutes ± 10 minutes).

After the 5th week, your doctor will administer a dose ofEpysqli dilutedof up to 1200mg every 2 weeks as long-term treatment.

For children and adolescents

Children and adolescentswith HPN or SHUawith a weight of 40 kg or more will be treated with the adult dose.

Children and adolescentswith HPN or SHUawith 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 adolescentswith HPN or SHUaunder 18 years:

After each infusion, you must remain under observation for 1 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 been accidentally administered a dose of Epysqli greater than the prescribed dose, consult your doctor.

If you forget to attend a scheduled appointment to receive Epysqli

If you forget to attend a scheduled appointment, consult your doctor immediately and read the section “If you interrupt treatment with Epysqli”.

If you interrupt treatment with Epysqli in HPN

If you interrupt or stop treatment with Epysqli, it is possible that HPN symptoms will reappear more intensely just after interrupting treatment. If you interrupt treatment with Epysqli, your doctor will discuss possible side effects and explain the risks. In addition, they will closely monitor you for at least 8 weeks.

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

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

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

If you interrupt treatment with Epysqli in SHUa

If you interrupt or stop treatment withEpysqli, it is possible that SHUa symptoms will reappear. Your doctor will discuss possible side effects and explain the risks. In addition, they will closely monitor you.

The risks of interrupting treatment withEpysqliinclude an increase in the inflammatory processes of your platelets, which can cause the following:

• a significant decrease in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of your red blood cells;
• decreased urination (kidney problems);
• an increase in 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.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Your doctor will inform you about the possible side effects and explain the risks and benefits of Epysqli before starting treatment.

The most severe side effect was meningococcal sepsis (unknown frequency [cannot be estimated from available data]).

If you experience any of the symptoms of meningococcal infection (see section 2 “Meningococcal infection alert and other Neisseria infections”), inform your doctor immediately.

If you are unsure about the side effects listed below, ask your doctor to explain them to you.

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

• headache.

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

• lung infection (pneumonia), common cold (nasopharyngitis), urinary tract infection (urinary tract infection);
• low white blood cell count (leucopenia), reduced red blood cell count that may cause paleness and cause 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), chills, feeling of fatigue (fatigue), flu-like illness;
• reaction related to perfusion.

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

• serious infection (meningococcal infection), infection, sepsis, septic shock, viral infection, lower respiratory tract infection, stomach 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 lymphocyte count (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), dizziness;
• 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), nasal bleeding, nasal congestion (nasal congestion), throat irritation, nasal discharge (rhinorrhea);
• peritoneal inflammation (tissue that covers most of the abdominal organs), constipation, postprandial abdominal discomfort (dyspepsia), abdominal distension;
• urticaria, skin redness or rashes, dry skin, red or purple spots on the skin, increased sweating, skin inflammation;
• muscle cramps, muscle pain, back pain and neck pain, bone pain;
• renal disorders, urinary difficulties or pain (dysuria), blood in urine;

• spontaneous erection;
• swelling (edema), chest discomfort, feeling of weakness (asthenia), chest pain, pain at the perfusion site, chills;
• increased liver enzymes, decreased proportion of blood volume occupied by red blood cells, decreased protein that transports oxygen in red blood cells;

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

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus influenzae infection, impetigo, sexually transmitted bacterial disease (gonorrhea);
• skin cancer (melanoma), bone marrow disorder;
• red blood cell destruction (hemolysis), cellular aggregation, abnormal coagulation factor, abnormal coagulation;
• hyperthyroidism (Basedow's disease);
• abnormal dreams;
• eye irritation;
• bruising;
• unusual reflux of food, gum pain;
• yellow discoloration of the skin and/or eyes (jaundice);
• skin color disorders;
• muscle spasms of the oral musculature, joint swelling;
• menstrual disorder;
• abnormal medication release from the vein, abnormal sensation at the perfusion site, feeling of heat.

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for the Pharmacovigilance of Medicines for Human Use: www.notificaRAM.es.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

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

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

Do not freeze.

Epysqli vials can be stored in the original container outside the refrigeratorfor a single period of up to 2 monthsat room temperature (up to 30°C), without exceeding the original expiration date. At the end of this period, the product can be stored in the refrigerator again.

Store in the original packaging to protect it from light.

After dilution, the medication 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 in aseptic (sterile) conditions, it can be stored in the refrigerator at between 2°C and 8°C for up to 3 months and for an additional 72 hours at room temperature (up to 30°C) when diluted with 9 mg/ml (0.9%) sodium chloride solution for injection, 4.5 mg/ml (0.45%) sodium chloride solution for injection.

Medicines should not be disposed of through the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Epysqli

• The active principle is eculizumab (300 mg/30 ml in a vial corresponding to 10 mg/ml).
• The other components are:
• • dihydrogen phosphate of sodium monohydrate (see section 2 “Epysqli contains sodium”)
  • hydrogen phosphate of disodium heptahydrate (see section 2 “Epysqli contains sodium”)
  • trehalose dihydrate
  • polysorbate 80

Vehicle: water for injectable preparations

Aspect of the product and content of the packaging

Epysqli is presented in the form of a concentrate for a perfusion solution (30 ml in a vial – packaging size of 1 vial).

Epysqli is a transparent and colorless solution.

Holder of the marketing authorization and responsible for manufacturing

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

Netherlands

Last review date of this leaflet: 03/2024

Other sources of information

The detailed information on this medicine is available on the website of the European Medicines Agency:http://www.ema.europa.eu.and on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)(http://www.aemps.gob.es/). There are also links to other websites on rare diseases and orphan drugs.

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Instructions for use for healthcare professionals

Handling of Epysqli

This information is intended solely for healthcare professionals.

1- How is Epysqli administered?

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

2- Before administering the medicine

The reconstitution and dilution must be carried out in accordance with good practices, especially in terms of asepsis.

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

• Visually inspect the Epysqli solution to check that it does not contain particles or color changes.
• Extract the necessary amount of Epysqli from the vial or vials using a sterile syringe.
• Transfer the recommended dose to a perfusion bag.
• Dilute Epysqli to a final concentration of 5 mg/ml (initial concentration divided by 2) by adding the appropriate amount of vehicle to the perfusion bag. To prepare a dose of 300 mg, use 30 ml of Epysqli (10 mg/ml) and add 30 ml of vehicle. For doses of 600 mg, use 60 ml of Epysqli and add the same volume of vehicle. For a dose of 900 mg, use 90 ml of Epysqli and add 90 ml of vehicle.For 1200mg use 120ml ofEpysqliand add 120ml of vehicle.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 mgor240ml for doses of 1200mg.
• Vehicle 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.
• Agitate the perfusion bag with the diluted Epysqli solution gently to ensure that the medicine and vehicle are well mixed.
• Allow the diluted solution to warm up to room temperature (up to 30°C) before administering it, by exposing it to the ambient air.
• The diluted solution should not be heated in the microwave or in any other heat source other than room temperature.
• Dispose of the remaining medicine in the vial.
• The diluted Epysqli solution can be stored between 2 °C-8 °C or at room temperature (up to 30 °C) for 24 hours once removed from the refrigerator.However, if the solution is prepared in aseptic conditions (sterile), it can be stored in the refrigerator at between 2°C and 8°C for up to 3months and for 72hours more at room temperature (up to 30°C) when diluted with sodium chloride 9mg/ml (0.9%) injectable solution, sodium chloride 4.5mg/ml (0.45%) injectable solution.

3- Administration

• Do not administer Epysqli by direct intravenous injection or by bolus injection.
• Epysqli can only be administered by intravenous perfusion.
• The diluted Epysqli solution will be administered by intravenous perfusion 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 a perfusion pump. No protection of the Epysqli diluted solution from light is required during administration to the patient.

The patient will remain under observation for one hour after perfusion. If an adverse effect occurs during administration of Epysqli, the perfusion should be interrupted or the rate reduced, as deemed necessary by the doctor. If the rate is reduced, the total duration of perfusion should not exceed two hours in adults and not more than four hours in pediatric patients under 18 years of age.

4- Special conditions for conservation and handling

Store in the refrigerator (between 2 °C and 8 °C). Do not freeze. Store in the original packaging to protect it from light. The Epysqli vials can be kept 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 stored in the refrigerator.

Do not use this medicine after the expiration date that appears on the boxand on the label of the vialafter “CAD”. The expiration date is the last day of the month indicated.