Soliris 300 mg concentrate for solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Soliris 300 mg concentrate for solution for infusion

eculizumab

Read the entire 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 other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse reactions, consult your doctor, pharmacist or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Soliris is and what it is used for

What Soliris is

The active substance in Soliris is eculizumab, which 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 Soliris is used for

Paroxysmal nocturnal hemoglobinuria

Soliris is used to treat adult and pediatric patients with a specific blood disorder called paroxysmal nocturnal hemoglobinuria (PNH). In patients with PNH, red blood cells may be destroyed, leading to a reduction in red blood cell count (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 vulnerable PNH blood cells.

Atypical hemolytic uremic syndrome

Soliris is also used to treat adult and pediatric patients with a certain blood and kidney disorder called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, the kidneys and blood cells, including platelets, may be damaged, leading 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.

Refractory generalized myasthenia gravis

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

Neuromyelitis optica spectrum disorder

Soliris is also used to treat adult patients with a disorder primarily affecting the optic nerves and spinal cord called neuromyelitis optica spectrum disorder (NMOSD). In patients with NMOSD, the immune system attacks and damages the nerves in the eyes and spinal cord, potentially causing blindness in one or both eyes, weakness or paralysis in the arms or legs, painful spasms, loss of sensation, and significant impairment in daily activities. Soliris can block the body's inflammatory response and its ability to attack and destroy the nerves in the eyes and spinal cord, thereby reducing disease symptoms and the impact of the disease on daily activities.

2. What you need to know before using Soliris

Do not use Soliris

• If you are allergic to eculizumab, to mouse-derived proteins, to other monoclonal antibodies, or to 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 up to 2 weeks after vaccination.
• If you currently have a meningococcal infection.

Warnings and precautions

Meningococcal infection and other Neisseria infections alert

Treatment with Soliris may reduce your body's natural defenses against infections, particularly against certain organisms that cause meningococcal infection (a serious infection of the lining of the brain and sepsis) and other Neisseria infections, including disseminated gonorrhea.

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

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

Symptoms of meningococcal infection

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

If you experience any of the following symptoms, contact 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

Meningococcal infection treatment during travel

If you plan to travel to a remote area where you cannot easily contact your doctor or access medical care, 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, take the prescribed antibiotic immediately. Remember that you must seek medical attention as soon as possible, even if you feel better after taking the antibiotic.

Infections

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

Allergic reactions

Soliris 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 patients

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

Other medicines and Soliris

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take 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

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

Soliris contains sodium

When reconstituted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.88 g of sodium (the main component of table/cooking salt) in 240 ml at the maximum dose. This corresponds to 44% of the maximum daily recommended 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 0.67 g of sodium (the main component of table/cooking salt) in 240 ml at the maximum dose. This corresponds to 33.5% of the maximum daily recommended sodium intake for an adult. This should be taken into account if you are on a low-sodium diet.

Soliris contains polysorbate 80

This medicine contains 6.6 mg of polysorbate 80 per vial (30 ml vial), equivalent to 0.66 mg/kg or less of the maximum dose for adult patients and pediatric patients weighing over 10 kg, and equivalent to 1.32 mg/kg or less of the maximum dose for pediatric patients weighing 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 Soliris

At least 2 weeks before starting treatment with Soliris, your doctor will give you a meningococcal infection vaccine if you have not been previously vaccinated or if your previous vaccination has expired. If your child is younger than the recommended age for vaccination or if you have not been vaccinated at least 2 weeks before starting Soliris treatment, your doctor will prescribe antibiotics to reduce the risk of infection for up to 2 weeks after vaccination.

Your doctor will administer to your child under 18 years of age vaccines against Haemophilus influenzae and pneumococcal infections according to current local vaccination guidelines 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 from the Soliris vial prepared in an infusion bag, delivered through a small tube directly into a vein. The initial phase of treatment is recommended to last 4 weeks, after which the maintenance phase will begin:

If you are using this medicine to treat PNH

For adults:

• Induction phase:

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

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

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

For adults:

• Induction phase:

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

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

Children and adolescents with PNH, aHUS, or refractory gMG who weigh 40 kg or more will receive the adult dose.

Children and adolescents with PNH, aHUS, or refractory gMG who weigh less than 40 kg require a lower dose based on body weight. Your doctor will calculate it.

For children and adolescents under 18 years of age with PNH or aHUS:

Patients undergoing plasma exchange may receive additional doses of Soliris.

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

If you have received more Soliris than you should

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

If you forget to attend an appointment for Soliris infusion

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

If you interrupt treatment with Soliris in PNH

If you interrupt or discontinue treatment with Soliris, 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.

Risks of interrupting treatment with Soliris include an increased destruction of your red blood cells, which may lead to:

• 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 Soliris in aHUS

If you interrupt or discontinue treatment with Soliris, 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.

Risks of interrupting treatment with Soliris include increased inflammatory processes affecting your platelets, which may lead to:

• A marked decrease in platelet count (thrombocytopenia),
• A significant increase in destruction of 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 interrupt treatment with Soliris for refractory gMG

If you interrupt or discontinue treatment with Soliris, symptoms of gMG may reappear. Talk to your doctor before stopping treatment with Soliris. Your doctor will discuss the possible adverse effects and risks with you. In addition, you will be closely monitored.

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

If you interrupt treatment with Soliris for NMOSD

If you interrupt or discontinue treatment with Soliris, NMOSD may worsen and a relapse may occur. Talk to your doctor before stopping treatment with Soliris. Your doctor will discuss the possible adverse effects and risks with you. In addition, you will be closely monitored.

If you have any further questions about 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 everyone will experience them. Your doctor will discuss the possible adverse effects with you 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 meningococcal infection (see section 2, Meningococcal infection warning and other Neisseria infections), inform your doctor immediately.

If you are unsure about any of 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 (leukopenia), reduced 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 tired (fatigue), flu-like illness
• infusion-related reaction

Uncommon: may affect up to 1 in 100 patients:

• 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 lymphocyte count, 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
• tingling sensation in part of the body (paresthesia), tremor, taste disturbance (dysgeusia), fainting
• blurred vision
• ringing in the ears, dizziness (vertigo)
• 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
• hives, 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 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
• hyperactive thyroid disease (Graves' disease)
• abnormal dreams
• eye irritation
• bruising
• unusual backflow of infused medicine from the 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 type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect 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 Soliris

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiry date which is 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.

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

Do not freeze.

Soliris vials may be kept outside the refrigerator in their original packaging for a single period of up to 3 days. At the end of this period, the product may be returned to the refrigerator.

Keep in the original packaging to protect from light.

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

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

6. Contents of the pack and other information

Composition of Soliris

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

• The other components are:

• monobasic sodium phosphate (E 339)

• dibasic sodium phosphate (E 339)

• sodium chloride

• polysorbate 80 (E 433) (of vegetable origin)

• solvent: water for injections

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

Appearance of the product and contents of the pack

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

Soliris is a clear, colourless solution.

Marketing Authorisation Holder

Alexion Europe SAS

103-105 rue Anatole France

92300 Levallois-Perret

France

Manufacturer

Almac Pharma Services Limited

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

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

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 Health Products (AEMPS) (https://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 Soliris

This information is intended solely for physicians or healthcare professionals.

1- How is Soliris supplied?

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

2- Before administering the medicine

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

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

• Visually inspect the Soliris solution to ensure it contains no particles or discoloration.
• Withdraw the required amount of Soliris from the vial(s) 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 300 mg dose, use 30 ml of Soliris (10 mg/ml) and add 30 ml of diluent. For a 600 mg dose, 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 1200 mg dose, use 120 ml of Soliris and add 120 ml of diluent. The final volume of diluted Soliris solution at 5 mg/ml is 60 ml for 300 mg doses, 120 ml for 600 mg doses, 180 ml for 900 mg doses, and 240 ml for 1200 mg doses.
• Acceptable diluents include 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.
• Gently agitate the infusion bag containing the diluted Soliris solution to ensure the medication and diluent are well mixed.
• Allow the diluted solution to reach room temperature (between 18°C and 25°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 Soliris solution may be stored at 2°C to 8°C for up to 24 hours prior to administration.

3- Administration

• Do not administer Soliris by direct intravenous injection or by bolus injection.
• Soliris must 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 over 1 to 4 hours in pediatric patients under 18 years of age, using gravity drip, syringe pump, or infusion pump. The diluted Soliris 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 Soliris, the infusion may be interrupted or its rate reduced, at the physician's discretion. If the infusion rate is reduced, the total duration of infusion must not 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. Keep in the original packaging to protect from light.

Soliris vials may be kept outside the refrigerator in the original packaging for a single period of up to 3 days. At the end of this period, the product may be returned to refrigerated storage.

Do not use Soliris 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.