Epyseli 300 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Epysqli 300 mg concentrate for solution for infusion

eculizumab

This medicinal product is subject to additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Information on how to report side effects is provided at the end of section 4.

Read all of this leaflet carefully before you start using this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any side effects, talk to your doctor, pharmacist or nurse, even if they are side effects not listed in this leaflet. See section 4.

Leaflet contents

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

1. What Epysqli is and what it is used for

What Epysqli is

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, thereby preventing the body's systems from attacking and destroying vulnerable blood cells, kidneys, muscles, or nerves in the eyes and spinal cord.

What Epysqli is used for

Paroxysmal nocturnal hemoglobinuria

Epysqli is used to treat adult and pediatric patients with a specific type of blood disorder called paroxysmal nocturnal hemoglobinuria (PNH). In patients with PNH, red blood cells may be destroyed, which can lead to 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 in PNH.

Atypical hemolytic uremic syndrome

Epysqli is also used to treat adult and pediatric patients with a certain type of disease affecting the blood and kidneys called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, the kidneys and blood cells, including platelets, may be damaged, which can lead to low blood counts (thrombocytopenia and anemia), reduced or loss of kidney function, blood clots, fatigue, and impaired normal functioning. Eculizumab can block the body's inflammatory response and its ability to attack and destroy its own vulnerable blood and kidney cells.

2. What you need to know before using Epysqli

Do not use Epysqli

• If you are allergic to eculizumab, mouse-derived proteins, other monoclonal antibodies, or any of the other components of this medicine (listed in section 6).
• If you have not been vaccinated against meningococcal infection, unless you are receiving antibiotic treatment to reduce the risk of infection for 2 weeks after vaccination.
• If you currently have a meningococcal infection.

Warnings and precautions

Warning about meningococcal infection and other Neisseria infections

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

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

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

Symptoms of meningococcal infection

Because rapid identification and treatment of certain infections are critical in patients receiving Epysqli, you will be given a card listing specific symptoms of these infections to carry with you at all times. This is called the “Patient Card”.

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

• Headache accompanied by nausea or vomiting
• Headache accompanied by neck or back stiffness
• Fever
• Rash
• Confusion
• Severe muscle pain combined with flu-like symptoms
• Sensitivity to light

Management of meningococcal infection during travel

If you plan to travel to a remote area where you cannot easily contact your doctor or access medical treatment, your doctor may take appropriate preventive measures, such as providing you with a prescription for an antibiotic against Neisseria meningitidis to carry with you. If you develop any of the symptoms listed above, 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 active infection.

Allergic reactions

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

Children and adolescents

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

Elderly people

No special precautions are required for treatment in patients aged 65 years and older.

Other medicines and Epysqli

Inform your doctor or pharmacist if you are currently using, have recently used, or might need to use any other medicines.

Pregnancy, breastfeeding, and fertility

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

Women of childbearing potential

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

Pregnancy/breastfeeding

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

Driving and using machines

The effect of Epysqli on the ability to drive and use machines is negligible or none.

Epysqli contains sodium

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

When reconstituted with sodium chloride 4.5 mg/ml (0.45%) solution for injection, this medicine contains 0.26 g of sodium in 240 ml at the maximum dose. This corresponds to 12.8% of the maximum recommended daily sodium intake for an adult. This should be taken into account 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 body weight above 10 kg, and equivalent to 1.32 mg/kg or less of the maximum dose for pediatric patients with body weight of 5 to <10 kg. Polysorbates may cause allergic reactions. Inform your doctor if you or your child has any known allergies.

3. How to use Epysqli

At least 2 weeks before starting treatment with Epysqli, your doctor will administer a meningococcal infection vaccine if you have not been previously vaccinated or if your previous vaccination has expired. If your child is below 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 for up to 2 weeks after vaccination.

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

Instructions for proper use

Your doctor or another healthcare professional will administer the treatment, which consists of an intravenous infusion of a diluted solution prepared from the Epysqli vial into an infusion bag, delivered through a small 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 HPN

For adults:

• Initial phase:

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

• Maintenance phase:

• In week five, your doctor will administer an intravenous infusion of diluted Epysqli corresponding to a dose of 900 mg (3 vials of 30 ml) over approximately 25–45 minutes (35 minutes ± 10 minutes).

• After week five, your doctor will administer 900 mg of diluted Epysqli every two weeks as long-term treatment.

If you are using this medicine to treat SHUa

For adults:

• Initial phase:

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

• Maintenance phase:

• In week five, your doctor will administer an intravenous infusion of diluted Epysqli corresponding to a dose of 1200 mg (4 vials of 30 ml) over approximately 25–45 minutes (35 minutes ± 10 minutes).

• After week five, your doctor will administer 1200 mg of diluted Epysqli every two weeks as long-term treatment.

For children and adolescents

Children and adolescents with HPN or SHUa weighing 40 kg or more will be treated with the adult dose.

Children and adolescents with HPN or SHUa weighing less than 40 kg require a lower dose based on body weight. Your doctor will calculate it.

For children and adolescents with HPN or SHUa under 18 years of age:

Body weight	Initial phase	Maintenance phase
	600 mg weekly
30 to <40 kg	for the first	900 mg in week 3; then 900 mg every 2 weeks
	2 weeks
	600 mg weekly
20 to <30 kg	for the first	600 mg in week 3; then 600 mg every 2 weeks
	2 weeks
10 to <20 kg	Single dose of 600 mg in week 1	300 mg in week 2; then 300 mg every 2 weeks
5 to <10 kg	Single dose of 300 mg in week 1	300 mg in week 2; then 300 mg every 3 weeks

After each infusion, you must remain under observation for one hour and follow your doctor's instructions exactly.

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 forget to attend an appointment to receive Epysqli

If you miss an appointment, contact your doctor immediately and read the section “If you interrupt treatment with Epysqli”.

If you interrupt treatment with Epysqli in PNH

If you interrupt or stop treatment with Epysqli, symptoms of PNH may reappear more intensely shortly after stopping treatment. Your doctor will discuss the possible adverse effects and explain the risks to you. In addition, you will be closely monitored for at least 8 weeks.

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

• a marked decrease in red blood cell count (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 interrupt treatment with Epysqli in aHUS

If you interrupt or stop treatment with Epysqli, symptoms of aHUS may reappear. Your doctor will discuss the possible adverse effects and explain the risks to you. In addition, you will be closely monitored.

The risks of interrupting treatment with Epysqli include increased inflammatory processes in your platelets, which may cause the following:

• a marked decrease in platelet count (thrombocytopenia);
• a significant increase in the destruction of your red blood cells;
• reduced 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 may cause adverse effects, although not everyone experiences them. Your doctor will discuss the possible adverse effects with you 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 alert and other Neisseria infections”), inform your doctor immediately.

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

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

• headache

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

• lung infection (pneumonia), cold (nasopharyngitis), urinary tract infection (urinary infection)
• low white blood cell count (leukopenia), reduction in red blood cells that may cause paleness and lead to weakness or shortness of breath
• inability to sleep
• dizziness, high blood pressure
• upper respiratory tract infection, cough, sore throat (oropharyngeal pain), bronchitis, cold sores (herpes simplex)
• diarrhea, vomiting, nausea, abdominal pain, rash, hair loss (alopecia), itching (pruritus)
• joint pain (arms and legs), limb pain (arms and legs)
• fever (pyrexia), feeling of tiredness (fatigue), flu-like illness
• infusion-related reaction

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

• serious infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, stomach flu (gastrointestinal infection), cystitis
• infections, fungal infection, pus accumulation (abscesses), skin infection (cellulitis), influenza, sinusitis, dental infection (abscess), gum infection
• relatively low platelet count (thrombocytopenia), low level of lymphocytes (a specific type of white blood cells) (lymphopenia), sensation of palpitations
• severe allergic reactions causing difficulty breathing or dizziness (anaphylactic reaction), hypersensitivity
• loss of appetite
• depression, anxiety, mood changes, sleep disorder
• sensation of tingling in part of the body (paresthesia), tremor, taste disturbance (dysgeusia), fainting
• blurred vision
• ringing in the ears, dizziness
• sudden and rapid development of extremely high blood pressure, low blood pressure, hot flushes, venous disorders
• dyspnea (difficulty breathing), nosebleed, stuffy nose (nasal congestion), throat irritation, runny nose (rhinorrhea)
• inflammation of the peritoneum (the tissue lining most of the abdominal organs), constipation, stomach discomfort after meals (dyspepsia), abdominal distension
• increased liver enzymes
• urticaria, skin redness, dry skin, 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
• decrease in the proportion of blood volume occupied by red blood cells, decrease in the protein that carries oxygen in red blood cells

Rare (may affect up to 1 in 1,000 people):

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

Frequency not known: cannot be estimated from available data:

• liver damage

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system listed in Appendix V. By reporting adverse effects, you can help provide 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 expiry date stated on the carton and label of the vial after "EXP". The expiry date refers to the last day of the month indicated.

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

Do not freeze.

Vials of Epysqli may be kept in their 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 expiry date. At the end of this period, the product may be returned to refrigerated storage.

Keep in the original packaging to protect from light.

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

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Epysqli

• The active substance is eculizumab (300 mg/30 ml in a vial corresponding to 10 mg/ml).

• The other components are:

• monosodium 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 injections

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

Appearance of the product and contents of the pack

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

Epysqli is a clear, colourless solution.

Marketing Authorisation Holder and Manufacturer

Samsung Bioepis NL B.V.

Olof Palmestraat 10

2616 LR Delft

The Netherlands

Date of the most recent review of this summary:

Other sources of information

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 of Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/). There are also links to other websites about rare diseases and orphan medicinal products.

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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 supplied?

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

2- Before administering the medicine

Reconstitution and dilution must be carried out 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 contains no particles or discoloration.
• Withdraw the required amount of Epysqli from the vial(s) 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 300 mg dose, use 30 ml of Epysqli (10 mg/ml) and add 30 ml of diluent. For a 600 mg dose, use 60 ml of Epysqli and add 60 ml of diluent. For a 900 mg dose, use 90 ml of Epysqli and add 90 ml of diluent. For a 1200 mg dose, use 120 ml of Epysqli and add 120 ml of diluent. The final volume of a diluted Epysqli solution at 5 mg/ml is 60 ml for the 300 mg dose, 120 ml for the 600 mg dose, 180 ml for the 900 mg dose, or 240 ml for the 1200 mg dose.
• The diluents that may be used are sodium chloride 9 mg/ml (0.9%) solution for injection, sodium chloride 4.5 mg/ml (0.45%) solution for injection, or 5% glucose solution in water.
• Gently mix the infusion bag containing 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 leaving it at room temperature.
• The diluted solution must not be heated in a microwave or any other heat source other than room temperature.
• Discard any unused medicine remaining in the vial.
• The diluted Epysqli solution may be stored between 2 °C and 8 °C or at room temperature (up to 30 °C) for 24 hours after removal from the refrigerator. However, if the solution is prepared under aseptic (sterile) conditions, it may be stored in the refrigerator at 2 °C to 8 °C for up to 3 months and for an additional 72 hours at room temperature (up to 30 °C) when diluted with sodium chloride 9 mg/ml (0.9%) solution for injection or sodium chloride 4.5 mg/ml (0.45%) solution for injection.

3- Administration

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

The patient should remain under observation for one hour after the infusion. If an adverse reaction occurs during administration of Epysqli, the infusion may be interrupted or the infusion rate reduced, at the physician’s discretion. If the infusion rate is reduced, the total duration of the infusion must not exceed two hours in adults and four hours in paediatric 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. Keep in the original packaging to protect from light. Epysqli vials may be kept in their 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 expiry date. At the end of this period, the product may be returned to the refrigerator.

Do not use this medicine after the expiry date stated on the carton and on the label of the vial after “EXP”. The expiry date refers to the last day of the month indicated.