Prescribing Information: Information for the User

Soliris 300 mg Concentrate for Solution for Infusion

eculizumab

Read this entire prescribing information carefully before starting to use this medicine, as it contains important information for you.

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

What is Soliris

The active ingredient of Soliris 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 Soliris used for

Paroxysmal Nocturnal Hemoglobinuria (PNH)

Soliris is used in the treatment of adult and pediatric patients with a specific type of blood disorder 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, breathing difficulty, and blood clots. Eculizumab can block the body's inflammatory response and its ability to attack and destroy vulnerable PNH blood cells.

Atypical Hemolytic Uremic Syndrome (aHUS)

Soliris is also used for the treatment of adult and pediatric patients with a certain type of kidney and circulatory disorder called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, kidneys and blood cells, including platelets, can be damaged, leading to low blood counts (thrombocytopenia and anemia), decreased or lost kidney function, blood clots, fatigue, and functional difficulty. Eculizumab can block the body's inflammatory response and its ability to attack and destroy vulnerable blood cells and kidneys.

Generalized Myasthenia Gravis (gMG)

Soliris is also used to treat adult and pediatric patients 6 years of age or older with a certain type of muscle disorder called generalized myasthenia gravis (gMG). In patients with gMG, the immune system can attack and damage muscles, leading to significant muscle weakness, mobility deterioration, shortness of breath, extreme fatigue, risk of aspiration, and notable impairment of daily activities. Soliris can block the body's inflammatory response and its ability to attack and destroy its own muscles to improve muscle contraction, thus reducing disease symptoms and the impact of the disease on daily activities. Soliris is specifically indicated for patients who remain symptomatic despite receiving existing treatments for gMG.

Neuromyelitis Optica Spectrum Disorder (NMOSD)

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

No use Soliris

• If you are allergic to eculizumab, mouse-derived proteins, 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 vaccination.
• If you have a meningococcal infection.

Warnings and precautions

Meningococcal infection alert and other infections byNeisseria

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

Consult your doctor before using Soliris to ensure that you are vaccinated againstNeisseria meningitidis, one of the microorganisms that causes meningococcal infection, at least 2 weeksbefore starting treatment or that you receive antibiotic treatment to reduce the risk of infection until 2 weeks after vaccination. Make sure you are up to date on your meningococcal vaccinations. Also, note that vaccination does not always prevent this type of infection. According to 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.

Meningococcal infection symptoms

Given the importance of rapid identification and treatment of certain infections in patients receiving Soliris, 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:

• Headache accompanied by nausea or vomiting
• 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 Soliris, inform your doctor if you have any infections.

Allergic reactions

Soliris 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 required for the treatment of patients aged 65 years and older.

Other medications and Soliris

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 up to 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 Soliris on the ability to drive and operate machinery is negligible or insignificant.

Soliris contains sodium

Once diluted with 9 mg/ml (0.9%) sodium chloride solution for injection, this medication contains 0.88 g of sodium (main component of table salt/for cooking) in 240 ml at the maximum dose. This is equivalent to 44% 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 solution for injection, this medication contains 0.67 g of sodium (main component of table salt/for cooking) in 240 ml at the maximum dose. This is equivalent to 33.5% 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 Soliris, 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 Soliris, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after vaccination.

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 infusing a Soliris vial solution prepared in a drip bag, directly into a vein. It is recommended that the first 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 Soliris 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 Soliris 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 Soliris diluted every 2 weeks as long-term treatment.

If you use this medication to treat SHUa, MGg refractory or TENMO:

For adults:

• Initial phase:

During the first 4 weeks, your doctor will administer an intravenous infusion of Soliris diluted every week. Each administration will consist of a dose of up to 900 mg (3 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 Soliris diluted corresponding to a dose of up to 1200 mg (4 vials of 30 ml) for 25-45 minutes (35 minutes ± 10 minutes).
  • After the 5th week, your doctor will administer a dose of up to 1200 mg every 2 weeks as long-term treatment.

Children and adolescents with HPN, SHUa or MGg refractory and those with a weight of 40 kg or more will be treated with the adult dose.

Children and adolescents with HPN, SHUa or MGg refractory and those patients 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 HPN or SHUa under 18 years:

Patients undergoing plasma exchange may receive additional doses of Soliris.

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 Soliris than you should

If you suspect that you have been accidentally administered a dose of Soliris greater than the prescribed dose, consult your doctor.

If you forget to attend an appointment to receive Soliris

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

If you interrupt treatment with Soliris in HPN

If you interrupt or discontinue treatment with Soliris, it is possible that HPN symptoms will reappear more intensely just after interrupting treatment. If you interrupt treatment with Soliris, 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 Soliris include an increase in the destruction of your red blood cells, which may produce 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 Soliris in SHUa

If you interrupt or discontinue treatment with Soliris, 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 with Soliris include an increase in the inflammatory processes of your platelets, which may produce the following:

• a significant decrease in the number of platelets (thrombocytopenia);
• an 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.

If you interrupt treatment with Soliris for MGg refractory

If you interrupt or discontinue treatment with Soliris, it is possible that MGg symptoms will reappear. Talk to your doctor before interrupting treatment with Soliris. Your doctor will discuss possible side effects and risks. In addition, they will closely monitor you.

If you have any other questions about the use of this medication, ask your doctor, pharmacist or nurse.

If you interrupt treatment with Soliris for TENMO

If you interrupt or discontinue treatment with Soliris, it is possible that TENMO will worsen and a relapse will occur. Talk to your doctor before interrupting treatment with Soliris. Your doctor will discuss possible side effects and risks. In addition, they will closely monitor you.

If you have any other questions about the use of this medication, ask your doctor, pharmacist or nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Your doctor will discuss possible side effects and explain the risks and benefits of Soliris before starting treatment. The most severe side effect was meningococcal sepsis.

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 extremities (arms and legs);
• fever (pyrexia), chills, feeling of fatigue (fatigue), flu-like illness;
• infusion-related reaction

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, abscesses, skin infection (cellulitis), flu, sinusitis, dental infection (abscess), gum infection;
• relatively low platelet count (thrombocytopenia), low lymphocyte count (a type of white blood cell) (lymphopenia), 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), dizziness;
• 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, nasal bleeding, nasal congestion, throat irritation, nasal discharge (rhinorrhea);
• inflammation of the peritoneum (the tissue that covers most of the abdominal organs), constipation, postprandial abdominal discomfort (dyspepsia), abdominal distension;
• hives, 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, difficulty or pain while 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 transports oxygen in red blood cells;

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

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus influenzae infection, impetigo, sexually transmitted bacterial disease (gonorrhea);
• skin cancer (melanoma), bone marrow disorder;
• destruction of red blood cells (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 mouth, joint swelling;
• menstrual disorder;
• abnormal medication release from the vein, abnormal sensation at the infusion 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 the national notification system included in theAppendix V.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 on the 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.

Soliris vials can be stored in the original container outside the refrigeratorfor a singleperiod of up to 3 days.

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 medication must be used within 24 hours.

Medications should not be disposed of through 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 Soliris

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

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

Appearance of the product and contents of the packaging

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

Soliris is a transparent and colorless solution.

Holder of the marketing authorization

Alexion Europe SAS

103-105 rue Anatole France

92300 Levallois-Perret

France

Responsible for manufacturing

Almac Pharma Services

22 Seagoe Industrial Estate

Craigavon BT63 5QD

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 medication by contacting the local representative of the marketing authorization holder:

Spain

Alexion Pharma Spain, S.L.

Tel: +34 93 272 30 05

Last review date of this leaflet:

Other sources of information

The detailed information about this medication 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 drugs.

------------------------------------------------------------------------------------------------------------------Instructions for use for healthcare professionals

Handling of Soliris

This information is intended solely for doctors or healthcare professionals.

1- How is Soliris administered?

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

2- Before administering the medication

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

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

• Visually inspect the Soliris solution to check that it does not contain particles or color changes.
• Extract the required amount of Soliris from the vial or vials using a sterile syringe.
• Transfer the recommended dose to a perfusion bag.
• Dilute Soliris to a final concentration of 5 mg/ml (initial concentration divided by 2) by adding the appropriate amount of solvent to the perfusion bag. To prepare a dose of 300 mg, use 30 ml of Soliris (10 mg/ml) and add 30 ml of solvent. For doses of 600 mg, use 60 ml of Soliris and add the same volume of solvent. For a dose of 900 mg, use 90 ml of Soliris and add 90 ml of solvent. For 1200 mg, use 120 ml of Soliris and add 120 ml of solvent. 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 solvents that can be used are sodium chloride 9 mg/ml (0.9%) injection solution, sodium chloride 4.5 mg/ml (0.45%) injection solution, or 5% glucose solution in water.

Agitate the perfusion bag with the diluted Soliris solution gently to ensure that the medication and solvent are well mixed.

Allow the diluted solution to reach room temperature (between 18°C-25°C) before administering it, leaving it at room temperature.

The diluted solution should not be heated in a microwave oven or any other heat source other than room temperature.

Discard the remaining medication in the vial, as it does not contain preservatives.

The diluted Soliris solution can be stored at 2°C-8°C for a maximum of 24 hours before administering it.

3- Administration

• Do not administer Soliris by direct intravenous injection or by bolus injection.
• Soliris can only be administered by intravenous perfusion.
• The diluted Soliris solution will be administered by intravenous perfusion for 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 will remain under observation for one hour after perfusion. If an adverse effect occurs during Soliris administration, 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 cannot exceed two hours in adults and four hours in pediatric patients under 18 years of age.

4- Special storage and handling conditions

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 stored in the original packaging outside the refrigeratorfor 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 indicated on the packaging after “CAD”. The expiration date is the last day of the month indicated.