SOLIRIS 300 mg CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

Soliris 300 mg Concentrate for Solution for Infusion

eculizumab

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 Package Leaflet

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

1. What is Soliris and what is it used for

What is Soliris

The active substance of Soliris is eculizumab and it 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 Soliris is used for

Paroxysmal Nocturnal Hemoglobinuria

Soliris 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 PNH blood cells.

Atypical Hemolytic Uremic Syndrome

Soliris is also used to treat adult and child patients with a certain type of disease that affects the blood system and the 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.

Generalized Myasthenia Gravis

Soliris is also used to treat adult and child patients aged 6 years and older with a certain type of disease that affects the muscles called generalized myasthenia gravis (gMG). In patients with gMG, the immune system can attack and damage the muscles, which can cause profound muscle weakness, mobility impairment, shortness of breath, extreme fatigue, risk of aspiration, and significant impairment of daily activities. Soliris can block the body's inflammatory response and its ability to attack and destroy its own muscles, improving muscle contraction and reducing the symptoms of the disease and its impact on daily activities. Soliris is specifically indicated in patients who remain symptomatic despite receiving other existing treatments for gMG.

Neuromyelitis Optica Spectrum Disorder

Soliris is also used to treat adult patients with a certain type of disease that predominantly affects the nerves of the eyes and the spinal cord called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the immune system attacks and damages the nerves of the eyes and the spinal cord, which can cause blindness in one or both eyes, weakness or paralysis in the legs or arms, painful spasms, loss of sensation, and significantly impact daily activities. Soliris can block the body's inflammatory response and its ability to attack and destroy its own nerves of the eyes and spinal cord, reducing the symptoms of the disease and its impact on daily activities.

2. What you need to know before you use Soliris

Do not use Soliris

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

Consult your doctor before using Soliris to ensure that you are vaccinated against Neisseria meningitidis, one of the microorganisms that causes 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 complementary measures to avoid infection.

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

Symptoms of Meningococcal Infection

Given the importance of rapid identification and treatment of certain infections in patients being treated with Soliris, 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 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 Soliris, tell your doctor if you have any infection.

Allergic Reactions

Soliris 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 Soliris

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

Pregnancy, Breast-feeding, and Fertility

If you are pregnant or breast-feeding, 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 up to 5 months after treatment.

Pregnancy/Breast-feeding

If you are pregnant or breast-feeding, 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

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

Soliris Contains Sodium

Once diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.88 g of sodium (main component of cooking/table salt) in 240 ml at the maximum dose. This is equivalent to 44% 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 0.67 g of sodium (main component of cooking/table salt) in 240 ml at the maximum dose. This is equivalent to 33.5% 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.

Soliris 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 can cause allergic reactions. inform your doctor if you or child have any known allergy.< p>

3. How to Use Soliris

At least 2 weeks before starting treatment with Soliris, your doctor will administer a vaccine against meningococcal infection if you have not been vaccinated before or if the vaccine you were given 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 Soliris, 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 other healthcare professional will administer the treatment, which consists of the infusion of a diluted Soliris vial prepared in a drip bag, through a tube directly into a vein. It is recommended that the first phase of treatment, or initial phase, lasts 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 diluted Soliris 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 diluted Soliris corresponding to a dose of 900 mg (3 vials of 30 ml) over 25-45 minutes (35 minutes ± 10 minutes).
  • After the fifth week, your doctor will administer 900 mg of diluted Soliris every 2 weeks as long-term treatment.

If you are using this medicine to treat aHUS, gMG, or NMOSD:

For adults:

• Initial phase:

During the first four weeks, your doctor will administer an intravenous infusion of diluted Soliris 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 diluted Soliris corresponding to a dose of 1200 mg (4 vials of 30 ml) over 25-45 minutes (35 minutes ± 10 minutes).
  • After the fifth week, your doctor will administer 1200 mg of diluted Soliris every 2 weeks as long-term treatment.

Children and adolescents with PNH, aHUS, or gMG and weighing 40 kg or more will be treated with the adult dose.

Children and adolescents with PNH, aHUS, or gMG and weighing 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:

Patient undergoing plasma exchange may receive additional doses of Soliris.

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 Soliris than you should

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

If you miss an appointment to receive Soliris

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

If you stop treatment with Soliris for PNH

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

The risks of stopping treatment with Soliris 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 Soliris for aHUS

If you stop or discontinue treatment with Soliris, it is possible that aHUS symptoms may reappear. Your doctor will discuss the possible side effects and risks with you and will closely monitor you.

The risks of stopping treatment with Soliris 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.

If you stop treatment with Soliris for gMG

If you stop or discontinue treatment with Soliris, gMG symptoms may reappear. Talk to your doctor before stopping treatment with Soliris. Your doctor will discuss the possible side effects and risks with you and will closely monitor you.

If you stop treatment with Soliris for NMOSD

If you stop or discontinue treatment with Soliris, NMOSD may worsen and relapse. Talk to your doctor before stopping treatment with Soliris. Your doctor will discuss the possible side effects and risks with you and will closely monitor you.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist, or nurse.

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 Soliris before starting treatment. The most serious adverse effect was meningococcal sepsis.

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

If you are unsure about the adverse 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), 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
• inability to sleep
• 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, 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), tremors, taste disorder (dysgeusia), fainting
• blurred vision
• ringing in the ears, vertigo
• sudden and rapid development of extremely high blood pressure, low blood pressure, hot flashes, venous disorders
• shortness of breath (dyspnea), nosebleeds, stuffy nose (nasal congestion), throat irritation, nasal discharge (rhinorrhea)
• inflammation of the peritoneum (tissue that lines most abdominal organs), constipation, stomach upset after eating (dyspepsia), abdominal distension
• hives, skin redness, dry skin, red or purple spots on the skin, increased sweating, skin inflammation

• muscle cramps, 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
• destruction of red blood cells (hemolysis), cellular aggregation, abnormal coagulation factor, abnormal coagulation
• disease with hyperthyroidism (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 sensation at the infusion site, sensation of heat

Reporting Adverse Effects

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 prospectus. You can also report them directly through the national notification system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Conservation of Soliris

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 on the label of the vial 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.

Soliris vials can be kept in the original packaging outside the refrigerator for a single period of up to 3 days.

At the end of this period, the product can be returned to the refrigerator.

Keep in the original packaging to protect it from light.

After dilution, the medicine must be used within 24 hours.

Medicines should not be thrown away 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

Soliris Composition

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

• Other components are:
• • sodium phosphate monobasic
  • sodium phosphate dibasic
  • sodium chloride
  • polysorbate 80 (of vegetable origin)
  • solvent: water for injectable preparations

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

Product Appearance and Package Contents

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

Soliris is a clear and colorless solution.

Marketing Authorization Holder

Alexion Europe SAS

103-105 rue Anatole France

92300 Levallois-Perret

France

Manufacturer

Almac Pharma Services

22 Seagoe Industrial Estate

Craigavon BT63 5UA

United Kingdom

Alexion Pharma International

Operations Limited

College Business and Technology Park

Blanchardstown Road North

Dublin 15

D15 R925

Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the Last Revision of this Prospectus:04/2025.

Other Sources of Information

Detailed information about 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 Health Products (AEMPS) (https://www.aemps.gob.es/). There are also links to other websites about rare diseases and orphan medicines.

------------------------------------------------------------------------------------------------------------------Instructions for Healthcare Professionals

Handling of Soliris

This information is intended only for doctors or healthcare professionals.

1- How is Soliris Supplied?

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

2- Before Administering the Medicine

Reconstitution and dilution must be performed according to good practice standards, especially regarding asepsis.

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

• Visually inspect the Soliris solution to ensure it does not contain particles or color changes.
• Withdraw the required amount of Soliris from the vial or vials using a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute Soliris 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 Soliris (10 mg/ml) and add 30 ml of diluent. For a dose of 600 mg, use 60 ml of Soliris and add 60 ml of diluent. For a dose of

900 mg, use 90 ml of Soliris and add 90 ml of diluent. For a dose of 1200 mg, use 120 ml of Soliris and add 120 ml of diluent. The final volume of a diluted Soliris 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 glucose solution 5% in water.

• Gently shake the infusion bag with the diluted Soliris solution to ensure the medicine and diluent are well mixed.
• Allow the diluted solution to reach room temperature (between 18°C-25°C) before administration, leaving it at room temperature.
• The diluted solution should not be heated in the microwave or any other heat source other than room temperature.
• Discard the medicine remaining in the vial.
• The diluted Soliris solution can be stored between 2°C and 8°C for a maximum of 24 hours before administration.

3- Administration

• Do not administer Soliris by direct intravenous injection or by bolus injection.
• Soliris should only be administered by intravenous infusion.
• The diluted Soliris 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, syringe pump, or infusion pump. It is not necessary to protect the diluted Soliris solution from light during administration to the patient.

The patient should remain under observation for one hour after infusion. If an adverse effect occurs during the administration of Soliris, 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 Conditions for Storage 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.

Soliris vials can be kept in the original packaging outside the refrigerator for a single period of up to 3 days.

At the end of this period, the product can be returned to the refrigerator.

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