Soliris

Package leaflet: Information for the user

Soliris 300 mg concentrate for solution for infusion

Eculizumab
Please 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 questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

1. What Soliris is and what it is used for
2. What you need to know before using 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
Soliris contains the active substance eculizumab and belongs to a class of medicines known as
monoclonal antibodies. Eculizumab binds to a specific protein in the body that causes
inflammation, and by inhibiting its action, prevents certain body systems from attacking and destroying vulnerable blood cells, kidneys, muscles, optic nerves, and the spinal cord.

What Soliris is used for

Paroxysmal nocturnal haemoglobinuria (PNH)
Soliris is used to treat adult and pediatric patients with a blood disorder called paroxysmal nocturnal haemoglobinuria (PNH). In patients with PNH, red blood cells can be destroyed, leading to a reduced number of red blood cells (anaemia), fatigue, functional impairment, pain, dark urine, shortness of breath, and blood clots.
Eculizumab can block the body's inflammatory response and its ability to attack and destroy vulnerable PNH red blood cells.

Atypical haemolytic uraemic syndrome (aHUS)
Soliris is also used to treat adult and pediatric patients with a disorder affecting the blood system and kidneys called atypical haemolytic uraemic syndrome (aHUS). In patients with aHUS, the kidneys and blood cells, including platelets, may become inflamed; this leads to a reduced number of blood cells (thrombocytopenia and anaemia), reduced or lost kidney function, blood clots, fatigue, and functional impairment. Eculizumab is able to block the body's inflammatory response and its ability to attack and destroy vulnerable blood and kidney cells.

Refractory generalized myasthenia gravis (gMG)
Soliris is also used to treat adult and pediatric patients aged 6 years and older with a type of muscle disorder called generalized myasthenia gravis (gMG). In patients with gMG, muscles can be attacked and damaged by the immune system, resulting in profound muscle weakness, impaired mobility, breathlessness, extreme fatigue, risk of aspiration, and significant limitation 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 impact on daily activities. Soliris is specifically indicated for patients who remain symptomatic despite treatment with other existing therapies for MG.

Neuromyelitis optica spectrum disorder (NMOSD)
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 optic nerve and spinal cord are attacked and damaged by the immune system, potentially leading to blindness in one or both eyes, weakness or paralysis of the legs or arms, 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 optic nerves and spinal cord, thereby reducing disease symptoms and their impact on daily life.

2. What you need to know before using 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 are taking antibiotics to reduce the risk of infection for two weeks after vaccination;
• if you currently have a meningococcal infection.

Warnings and precautions
Alert regarding meningococcal infection and other Neisseria infections
Treatment with Soliris may reduce your body's natural defenses against infections, especially against certain microorganisms that cause meningococcal infection (a serious infection of the brain lining and sepsis) and other infections caused by Neisseria, including disseminated gonorrhea.
Talk to your doctor before starting Soliris to ensure you receive vaccination against Neisseria meningitidis, the organism responsible for meningococcal infection, at least 2 weeks before starting treatment or take antibiotics to reduce the risk of infection for two weeks after vaccination. Check that your meningococcal vaccination is up to date. However, you should be aware that vaccination may not prevent this type of infection. According to national recommendations, your doctor may consider it necessary to take additional preventive measures.
If you are at risk of gonorrhea, consult your doctor or pharmacist before taking this medicine.

Symptoms of meningococcal infection
Because it is important to identify and treat certain infections quickly in patients treated with Soliris, you will be given a card to carry with you listing specific symptoms to watch for. This card is called: “Patient Alert Card”.
If you experience any of the following symptoms, you must immediately contact your doctor:

• headache with nausea or vomiting;
• headache with neck or back stiffness;
• fever;
• skin rash;
• confusion;
• severe muscle pain with flu-like symptoms;
• sensitivity to light.

Treatment of meningococcal infection while travelling
If you are planning to travel to a remote country where you may not be able to contact your doctor or where you may temporarily lack access to medical treatment, your doctor may prescribe, as a preventive measure, an antibiotic active against Neisseria meningitidis for you to carry with you. If you experience any of the symptoms listed above, you must take the antibiotics as prescribed.
Remember to consult a doctor as soon as possible, even if you feel better after taking the antibiotics.

Infections
Before starting treatment with Soliris, inform your doctor if you currently 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 of age should be vaccinated against Haemophilus influenzae and pneumococcal infections.

Elderly patients
No special precautions are required for patients aged 65 years or older.

Other medicines and Soliris
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine.

Women of childbearing potential
The use of effective contraceptive methods during treatment and for up to 5 months after treatment ends should be considered in women of childbearing potential.

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

Driving and using machines
Soliris has no effect or a negligible effect on the ability to drive and use machines.

Soliris contains sodium
When diluted with a 9 mg/mL (0.9%) sodium chloride injection solution, this medicine contains 0.88 g of sodium (the main component of table salt) per 240 mL at the maximum dose. This corresponds to 44% of the recommended maximum daily dietary intake for an adult. You should take this into account if you are on a low-sodium diet.
When diluted with a 4.5 mg/mL (0.45%) sodium chloride injection solution, this medicine contains 0.67 g of sodium (the main component of table salt) per 240 mL at the maximum dose. This corresponds to 33.5% of the recommended maximum daily dietary intake for an adult. You should take this 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 at the maximum dose for adult patients and pediatric patients weighing more than 10 kg, and equivalent to 1.32 mg/kg or less at the maximum dose for pediatric patients weighing between 5 and <10 kg. Polysorbates may cause allergic reactions. Inform your doctor if you or your child have known allergies.

3. How to use Soliris

At least two weeks before starting treatment with Soliris, your doctor will administer a vaccine against meningococcal infection, if you have not already been vaccinated or if your vaccination has expired. If your child is not yet of vaccinable age or if vaccination has not been performed at least two weeks before starting Soliris treatment, your doctor will prescribe antibiotics to reduce the risk of infection for up to two weeks after vaccination.
Your doctor will vaccinate your child, under 18 years of age, against Haemophilus influenzae and pneumococcal infections according to national vaccination recommendations for each age group.

Instructions for proper administration
Treatment will be administered by your doctor or another healthcare professional through an intravenous infusion of a diluted solution from a vial of Soliris directly into a vein. It is recommended that treatment begin with an initial phase lasting 4 weeks, followed by a maintenance phase:

If you are using this medicine to treat aHUS (atypical hemolytic uremic syndrome):
For adults:

• Initial phase: For the first four weeks, once weekly, your doctor will administer an intravenous infusion of a diluted solution of Soliris. Each infusion will consist of a dose of 600 mg (two vials of 30 mL) and will last 25–45 minutes (35 minutes ± 10 minutes).
• Maintenance phase:
  • In the fifth week, your doctor will administer an intravenous infusion of a diluted solution of Soliris at a dose of 900 mg (three vials of 30 mL) over 25–45 minutes (35 minutes ± 10 minutes).
  • From the sixth week onward, your doctor will administer 900 mg of diluted Soliris solution every two weeks as long-term therapy.

If you are using this medicine to treat PNH (paroxysmal nocturnal hemoglobinuria), refractory gMG (generalized myasthenia gravis), or NMOSD (neuromyelitis optica spectrum disorder):
For adults:

• Initial phase: For the first four weeks, once weekly, your doctor will administer an intravenous infusion of a diluted solution of Soliris. Each infusion will consist of a dose of 900 mg (three vials of 30 mL) and will last 25–45 minutes (35 minutes ± 10 minutes).
• Maintenance phase:
  • In the fifth week, your doctor will administer an intravenous infusion of a diluted solution of Soliris at a dose of 1,200 mg (four vials of 30 mL) over 25–45 minutes (35 minutes ± 10 minutes).
  • From the sixth week onward, your doctor will administer 1,200 mg of diluted Soliris solution every two weeks as long-term therapy.

Children and adolescents with aHUS, PNH, or refractory gMG who weigh 40 kg or more receive the same dosage as adults.
Children and adolescents with aHUS, PNH, or refractory gMG who weigh less than 40 kg require a lower dose based on body weight. Your doctor will calculate the appropriate dose.

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

Patients undergoing plasma exchange may receive an additional dose of Soliris.
After each infusion, you will be monitored for approximately one hour. You must carefully follow your doctor's instructions.

If you receive more Soliris than you should
If you suspect that you have received more Soliris than prescribed, consult your doctor for advice.

If you forget to attend a Soliris treatment appointment
If you miss an appointment, contact your doctor immediately and refer to the next section, “If you stop Soliris treatment”.

If you stop Soliris treatment for PNH
Stopping or interrupting therapy may rapidly lead to a recurrence of PNH symptoms in a more severe form. Your doctor will discuss with you the possible side effects and explain the risks. Your doctor will closely monitor you for at least 8 weeks.
Risks associated with discontinuation of Soliris include increased destruction of red blood cells, which may cause:

• a significant reduction in red blood cell count (anaemia);
• confusion or altered level of consciousness;
• chest pain or angina pectoris;
• increased serum creatinine levels (kidney problems); or
• thrombosis (blood clots). If you experience any of these symptoms, contact your doctor.

If you stop Soliris treatment for aHUS
Stopping or interrupting treatment with Soliris may cause a recurrence of aHUS symptoms. Your doctor will discuss with you the possible side effects and explain the risks. Your doctor will closely monitor you.
Risks associated with discontinuation of Soliris include increased platelet inflammation, which may cause:

• a significant reduction in platelet count (thrombocytopenia);
• a significant increase in red blood cell destruction;
• decreased urine output (kidney problems);
• increased serum creatinine levels (kidney problems);
• confusion or altered level of consciousness;
• chest pain or angina pectoris;
• shortness of breath; or
• thrombosis (blood clots).

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

If you stop Soliris treatment for refractory gMG
Stopping or interrupting treatment with Soliris may lead to a recurrence of gMG symptoms. Consult your doctor before stopping Soliris treatment. Your doctor will explain the possible side effects and risks, and will also closely monitor you.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

If you stop Soliris treatment for NMOSD
Stopping or interrupting treatment with Soliris may lead to worsening of NMOSD and the occurrence of relapse. Consult your doctor before stopping Soliris treatment. Your doctor will explain the possible side effects and risks, and will also closely monitor you.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them. Before treatment, your doctor will discuss with you the possible side effects and will explain the risks and benefits of Soliris.
The most serious side effect has been meningococcal sepsis.
If you experience any of the symptoms of meningococcal infection (see section 2 Meningococcal infection alert and other Neisseria infections), you must inform your doctor immediately.
If you are unsure about the side effects listed below, please ask your doctor for an explanation.

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

• headache

Common: may affect up to 1 in 10 people:

• lung infection (pneumonia), common cold (rhinopharyngitis), urinary tract infection (urinary tract infection)
• low white blood cell count (leucopenia), reduction in red blood cells that may make the skin pale and cause 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)
• diarrhoea, vomiting, nausea, abdominal pain, rash, hair loss (alopecia), itching
• 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 people:

• serious infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, gastroenteritis (gastrointestinal infection), cystitis
• infection, fungal infection, collection of pus (abscess), a type of skin infection (cellulitis), influenza, sinusitis, dental infection (abscess), gum infection
• relatively low platelet count in the blood (thrombocytopenia), low level of lymphocytes, a particular type of white blood cells (lymphopenia), awareness of heartbeat
• severe allergic reaction causing breathing difficulties or dizziness (anaphylactic reaction)
• hypersensitivity
• loss of appetite
• depression, anxiety, mood swings, sleep disorder
• tingling in part of the body (paraesthesia), tremor, disturbances in taste (dysgeusia), fainting
• blurred vision
• ringing in the ears, dizziness
• sudden and rapid onset of extremely high blood pressure, low blood pressure, hot flushes, venous disorder
• dyspnoea (difficulty breathing), nosebleed, stuffy nose (nasal congestion), throat irritation, runny nose (rhinorrhoea)
• inflammation of the peritoneum (the tissue lining most of the abdominal organs), constipation, stomach discomfort after meals (dyspepsia), abdominal distension
• increased levels of liver enzymes
• urticaria, skin redness, dry skin, red or purple spots under the skin, increased sweating, skin inflammation
• muscle cramp, muscle pain, back and neck pain, bone pain
• kidney disease, difficulty or pain when urinating (dysuria), blood in urine
• spontaneous penile erection
• swelling (oedema), chest discomfort, feeling of weakness (asthenia), chest pain, infusion site pain, chills
• decrease in the proportion of blood volume occupied by red blood cells, decrease in the protein in red blood cells that carries oxygen

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

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus infection, impetigo, sexually transmitted bacterial disease (gonorrhoea)
• skin tumour (melanoma), bone marrow disease
• destruction of red blood cells (haemolysis), cell aggregation, abnormal coagulation factor, abnormal blood clotting
• disease with overactivity of the thyroid gland (Graves' disease)
• abnormal dreams
• eye irritation
• bruising
• unusual regurgitation of food from the stomach, gum pain
• yellowing of the skin and/or eyes (jaundice)
• change in skin colour
• spasm of mouth muscles, joint swelling
• menstrual disorder
• abnormal leakage of infused drug outside the vein, abnormal sensation at infusion site, feeling of warmth

Not known: frequency cannot be estimated from the available data:

• Liver injury

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Soliris

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 on the label of the
vial after “Exp.”. The expiry date refers to the last day of that month.
Store in a refrigerator (2°C – 8°C).
Do not freeze.
Soliris vials in their original packaging may be removed from the refrigerator only once for a maximum of 3 days. At the end of this period, the product may be returned to the refrigerator.
Store in the original packaging to protect the medicine from light.
After dilution, use the medicine within 24 hours.
Do not dispose of any medicine via wastewater. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Soliris contains

• The active substance is eculizumab (300 mg/30 mL in a vial at 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.

Description of the appearance of Soliris and contents of the pack
Soliris is a concentrate for solution for infusion (30 mL in a vial – pack of 1 vial).
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

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien Lietuva
Alexion Pharma Belgium UAB AstraZeneca Lietuva
Tél/Tel: +32 0 800 200 31 Tel: +370 5 2660550

България Luxembourg/Luxemburg
АстраЗенека България ЕООД Alexion Pharma Belgium
Tel.: +359 24455000 Tél/Tel: +32 0 800 200 31

Česká republika Magyarország
AstraZeneca Czech Republic s.r.o. AstraZeneca Kft.
Tel: +420 222 807 111 Tel.: +36 1 883 6500

Danmark Malta
Alexion Pharma Nordics AB Alexion Europe SAS
Tlf.: +46 0 8 557 727 50 Tel: +353 1 800 882 840

Deutschland Nederland
Alexion Pharma Germany GmbH Alexion Pharma Netherlands B.V.
Tel: +49 (0) 89 45 70 91 300 Tel: +32 (0)2 548 36 67

Eesti Norge
AstraZeneca Alexion Pharma Nordics AB
Tel: +372 6549 600 Tlf: +46 (0)8 557 727 50

Ελλάδα Österreich
AstraZeneca A.E. Alexion Pharma Austria GmbH
Tel: +30 210 6871500 Tel: +41 44 457 40 00

España Polska
Alexion Pharma Spain, S.L.U. AstraZeneca Pharma Poland Sp. z o.o.
Tel: +48 22 245 73 00
Tel: +34 93 272 30 05

France Portugal
Alexion Pharma France SAS Alexion Pharma Spain, S.L. - Sucursal em Portugal
Tél: +33 1 47 32 36 21 Tel: +34 93 272 30 05

Hrvatska România
AstraZeneca d.o.o. AstraZeneca Pharma SRL
Tel: +385 1 4628 000 Tel: +40 21 317 60 41

Ireland Slovenija
Alexion Europe SAS AstraZeneca UK Limited
Tel: +353 1 800 882 840 Tel: +386 1 51 35 600

Ísland Slovenská republika
Alexion Pharma Nordics AB AstraZeneca AB, o.z.
Sími: +46 0 8 557 727 50 Tel: +421 2 5737 7777

Italia Suomi/Finland
Alexion Pharma Italy srl Alexion Pharma Nordics AB
Tel: +39 02 7767 9211 Puh/Tel: +46 0 8 557 727 50

Κύπρος Sverige
Alexion Europe SAS Alexion Pharma Nordics AB
Tel: +357 22490305 Tel: +46 0 8 557 727 50

Latvija
SIA AstraZeneca Latvija
Tel: +371 67377100

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/. In addition, links to other websites on rare diseases and their therapeutic treatments are provided.

Instructions for Use for Healthcare Professionals

Handling of Soliris
The following information is intended exclusively for healthcare professionals:

1- How is Soliris supplied?
Each vial of Soliris contains 300 mg of active substance in 30 mL of solution.

2- Prior to administration
Reconstitution and dilution must be performed in accordance with good practice standards, particularly maintaining aseptic conditions.
Soliris must be prepared for administration by a qualified healthcare professional using aseptic technique.

• Visually inspect the Soliris solution to ensure there are no particles or discoloration.
• Withdraw the required amount of Soliris from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute Soliris to a final concentration of 5 mg/mL (initial concentration divided by 2) by adding the appropriate volume of diluent to the infusion bag. For 300 mg doses, use 30 mL of Soliris (10 mg/mL) and add 30 mL of diluent. For 600 mg doses, use 60 mL of Soliris and add 60 mL of diluent. For 900 mg doses, use 90 mL of Soliris and add 90 mL of diluent. For 1,200 mg doses, use 120 mL of Soliris and add 120 mL of diluent. The final volume of the 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, or 240 mL for 1,200 mg doses. The acceptable diluents are sodium chloride 9 mg/mL (0.9%) injection solution, sodium chloride 4.5 mg/mL (0.45%) injection solution, or dextrose in water (5%).
• Gently mix the infusion bag containing the diluted Soliris solution to ensure thorough mixing of drug and diluent.
• Allow the diluted solution to warm to room temperature (18°C–25°C) before administration by leaving it at room temperature.
• The diluted solution must not be heated in a microwave or by any other heat source beyond room temperature.
• Discard any unused portion remaining in the vial.
• Diluted Soliris solutions may be stored at 2°C–8°C for up to 24 hours prior to administration.

3- Administration

• Do not administer Soliris as rapid intravenous injection or bolus.
• Soliris must be administered only by intravenous infusion.
• The diluted Soliris solution should be administered by intravenous infusion over 25–45 minutes (35 minutes ± 10 minutes) in adult patients and over 1–4 hours in pediatric patients under 18 years of age, using an infusion set, syringe pump, or infusion pump. The diluted Soliris solution does not need to be protected from light during administration. The patient should be monitored for one hour after the infusion. If an adverse event occurs during Soliris administration, the infusion may be slowed or stopped at the physician's discretion. If the infusion rate is reduced, the total infusion time should not exceed two hours in adults and four hours in pediatric patients under 18 years of age.

4- Special precautions for handling and storage
Store in a refrigerator (2°C–8°C). Do not freeze. Keep in the original packaging to protect the medicine from light. Soliris vials in their original packaging may be removed from the refrigerator only once for a maximum of 3 days. 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 packaging and on the vial label after the word “Exp.”. The expiry date refers to the last day of that month.