Soliris 300 mg concentrate for solution for infusion

The active substance of Soliris is eculizumab and it belongs to a class of medicines called monoclonal antibodies. Eculizumab binds to and inhibits a specific protein in the body that causes inflammation.

Soliris is used for the treatment of patients with a certain type of disease affecting the blood system called Paroxysmal Nocturnal Haemoglobinuria (PNH). In patients with PNH, their red blood cells can be destroyed which can lead to low blood counts (anaemia), tiredness, difficulty in functioning, pain, dark urine, shortness of breath, and blood clots. Eculizumab can block the body?s inflammatory response, and its ability to attack and destroy its own vulnerable PNH blood cells. There is only experience in the treatment of patients with previous history of transfusions.

Do not use Soliris

• If you are allergic (hypersensitive) to eculizumab, proteins derived from mouse products, have had an allergic reaction to other monoclonal antibodies, or any of the other ingredients of Soliris. (See Section 6, What Soliris contains).
• If you have not been vaccinated against meningitis infection.
• If you have a meningitis infection.
• If you have a disease that alters your immune system.

Take special care with Soliris

Meningitis alert:

Soliris treatment may reduce your natural resistance to infections, especially against certain organisms that cause meningitis.

Consult your doctor before you take Soliris to be sure that you receive vaccination against Neisseria meningitidis, an organism that causes meningitis, at least 2 weeks before beginning therapy, or that your current meningitis vaccination is up to date. You should also be aware that vaccination may not prevent this type of infection. In accordance with national recommendations, your doctor might consider that you need supplementary measures to prevent infection.

Meningitis symptoms
Because of the importance of rapidly identifying and treating certain types of infection in patients who receive Soliris, you will be provided a card to carry with you, listing specific trigger symptoms. This card is named: ?Patient Safety Card?.

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

• bothersome headache with nausea or vomiting
• bothersome headache with a stiff neck or back
• fever
• fever and a rash
• confusion
• severe muscle aches combined with flu-like symptoms
• sensitivity to light

Treatment for meningitis while travelling
If you are travelling in a remote region where you are unable to contact your doctor or in which you find yourself temporarily unable to receive medical treatment, your doctor can make arrangements to issue, as a preventive measure, a prescription for an antibiotic to counter Neisseria meningitidis that you keep with you. If you experience any of the symptoms amongst those cited above, you should take the antibiotics as prescribed. You should bear in mind that you should see a doctor as soon as possible, even if you feel better after having taken the antibiotics.

Infections

Inform your doctor before you take Soliris if you have any infections.

Allergic reactions

Soliris contains a protein and proteins can cause allergic reactions in some people.

Using Soliris with other medicines:

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Using Soliris with food and drink:

Interactions between your treatment with Soliris and food or drink are unlikely.

Woman of childbearing potential:

Women who are able to get pregnant should use adequate contraception methods during treatment and up to 5 months after treatment.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before using any medicine.

Pregnancy

Tell your doctor before starting treatment with Soliris if you are pregnant or plan to become pregnant. Soliris is not recommended during pregnancy.

Breast-feeding

Soliris may pass through your breast milk to your baby. Therefore, you should not breast-feed while using Soliris.

Driving and using machines:

The effects on the ability to drive and to use machines have not been studied. As with all medicines, you should ask for advice from your doctor.

Elderly people

There is no evidence to suggest that any special precautions are needed when older people (65 years and over) are treated ? although experience is still limited.

Children and adolescents
Soliris has not been administered to patients less than 18 years of age.

Important information about some of the ingredients of Soliris

This medicinal product contains 5.00 mmol sodium per dose (1 vial). To be taken into consideration by patients on a controlled sodium diet.

Prior to beginning treatment, your doctor will discuss with you the importance of:

• Receiving a vaccine against meningitis,
• Becoming knowledgeable about symptoms associated with infections, and
• Being carefully monitored by your doctor following any discontinuation of Soliris treatment.

At least 14 days before you start treatment with Soliris, your doctor will administer a vaccine against meningitis if it was not previously administered or if your vaccination is outdated.

Instructions for proper use

The treatment will be given by your doctor or other health care provider by infusing a dilution of the Soliris vial from a drip bag through a tube directly into one of your veins. It is recommended that the beginning of your treatments, called the initial phase, will extend over 5 weeks, followed by a maintenance phase:

Initial Phase:

- Every week for the first four weeks, your doctor will administer an intravenous infusion of diluted Soliris . Each infusion will consist of a dose of 600 mg (2 vials of 30 ml) and will take approximately 30 minutes.
- In the fifth week your doctor will administer an intravenous infusion of diluted Soliris at a dose of 900 mg (3 vials of 30 ml) over a 30 minute period.

Maintenance Phase:

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

Following each infusion, you will be monitored for about one hour. Your doctor?s instructions should be carefully observed.

If you receive more Soliris than you should

If you suspect that you have been accidentally administered a higher dose of Soliris than prescribed, please contact your doctor for advice.

If you forget an appointment to receive Soliris
If you forget an appointment, please contact your doctor immediately for advice and see section below ?If you stop using Soliris?.

If you stop usingSoliris
Interrupting or ending treatment with Soliris may cause your PNH symptoms to come back more severely soon after stopping Soliris treatment. If you stop treatment with Soliris, your doctor will discuss the possible side effects with you and explain the risks. Your doctor will want to continue to monitor you closely.

The risks of stopping Soliris include an increase in the destruction of your red blood cells, which may cause:

• A significant fall in your red blood cell counts (anaemia),
• You to be confused or unalert,
• Chest pain, or angina,
• An increase in your serum creatine level (problems with your kidneys), or
• Thrombosis (blood clotting).

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

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

Like all medicines, Soliris can cause side effects, although not everybody gets them. The side effects caused by Soliris are usually mild or moderate. Your doctor will discuss the possible side effects with you and explain the risks and benefits of Soliris with you prior to treatment.

If you are not sure what the side effects below are, ask your doctor to explain them to you.

Very common side effects
(occurring in at least 1 in 10 patients) include: headaches.

Common side effects
(occurring in 1 or more out of 100 patients and less than 10 in 100 patients) include: relatively few platelets in blood (thrombocytopenia), destruction of red blood cells (haemolysis), abdominal pain, constipation, vomiting, diarrhea, stomach discomfort after meals (dyspepsia), nausea, chest discomfort, chills, infusion related reaction, swelling (edema), fever (pyrexia), feeling tired (fatigue), feeling of weakness (asthenia), serious allergic reaction which causes difficulty in breathing or dizziness (anaphylactic reaction), cold sores (herpes simplex), common cold (nasopharyngitis), viral infection, stomach flu (gastrointestinal infection), bronchitis, cystitis, severe infection (sepsis, septic shock, meningococcal sepsis), infection of the joint (arthritis bacterial), infection of the lung (pneumonia), infection of the meninges (meningococcal meningitis), muscle aches, back and neck pain, pain in the limbs or joints (arms and legs), dizziness, taste disorders (dysgeusia), tingling in part of the body (paresthesia), difficulties or pain when urinating (dysuria), spontaneous penile erection, upper respiratory tract infection, infection of the urinary system (urinary tract infection), cough, throat irritation or pain (pharyngolaryngeal pain), stuffy nose (nasal congestion), itchy skin (pruritus), rash, hair loss (alopecia), dry skin.

Uncommon side effects

(occurring in 1 or more out of 1000 patients and less than 10 in 1000 patients) include: Abnormal blood clotting, clumping of cells, feeling your heartbeat, ringing in the ears, disease with thyroid overactivity (Basedow?s disease), irritation of eye, vision blurred, unusual backflow of food from stomach, gum pain, chest pain, influenza like illness, feeling hot, infusion site pain, yellowing of the skin and/or eyes (jaundice), collection of pus (abscess), type of infection of the skin (cellulitis), fungal infection, gum infection, infection, influenza, sinusitis, tooth infection, increase of liver enzymes, loss of appetite, spasm of mouth muscle, muscle cramp, skin tumor (melanoma), bone marrow disorder, fainting, abnormal dreams, anxiety, depression, inability to sleep, mood swings, sleep disorder, kidney disorder, menstrual disorder, nose bleed, runny nose, increased sweating, red or purple spots under the skin, skin color disorder, hives, bruise, low blood pressure, hot flush.

If any of these side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Store in a refrigerator (2°C ? 8-C).
Do not freeze.
Store in the original package in order to protect from light.
Do not use Soliris after the expiry date which is stated on the label after ?EXP?. After dilution, the product should be used immediately within 24 hours.

What Soliris contains

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

- The other ingredients are:

• sodium phosphate monobasic
• sodium phosphate dibasic
• sodium chloride
• polysorbate 80 (vegetable origin) Solvent: water for injections

What Soliris looks like 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 and colorless solution.

Marketing Authorisation Holder and Manufacturer :

Marketing Authorisation Holder:
Alexion Europe SAS
25 Boulevard de l?Amiral Bruix
75016 Paris
Tel: +33 (0) 1 53 64 38 00
France

Manufacturer:

Almac Pharma Service
22 Seagoe Industrial Estate
Craigavon BT63 5QD
United Kingdom

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

BelgiëBelgiqueBelgien Alexion Pharma Belgium Rue de la Régence 58 - 1000 Bruxelles Brussel Belgique België LuxembourgLuxemburg Alexion Pharma Belgium Rue de la Régence 58 - 1000 Bruxelles Belgique

TélTel 32 02 548 36 36 alexion.belgiumalxn.com TélTel 32 02 548 36 36 alexion.belgiumalxn.com

Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Magyarország Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Franciaország

Te. 33 0 1 53 64 39 50 alexion.francealxn.com Tel 33 0 1 53 64 39 50 alexion.francealxn.com

eská republika Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Francie Tel 33 0 1 53 64 39 50 alexion.francealxn.com Malta Alexion Pharma UK Unit 14, Horizon Business Village 1, Brooklands Road, Weybridge, Surrey KT13 OTJ UK Tel 44 0 1 932 35 9220 alexion.ukalxn.com

Danmark
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Bruxelles
Belgien

Nederland
Alexion Pharma Belgium Rue de la Régence 58 - 1000 Brussel België

Tlf: +32 (0)2 548 36 36
alexion.belgium@alxn.com

Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com

Deutschland Alexion Pharma Germany Arnulfstr. 19 80335 München Deutschland Norge Alexion Pharma Belgium Rue de la Régence 58 - 1000 Brussel Belgia

Tel 49 89 45 70 91 300 alexion.germanyalxn.com Tlf 32 02 548 36 36 alexion.belgiumalxn.com

Eesti Alexion Pharma Belgium Rue de la Régence 58 - 1000 Brüssel Belgia Österreich Alexion Pharma Germany Arnulfstr. 19 80335 München Deutschland Tel 32 02 548 36 36 alexion.belgiumalxn.com Tel 49 89 45 70 91 300 alexion.germanyalxn.com

Alexion Pharma Belgium Rue de la Régence 58 - 1000 Polska Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Francja

32 02 548 36 36 alexion.belgiumalxn.com Tel 33 0 1 53 64 39 50 alexion.francealxn.com

Portugal Alexion Pharma Belgium Rue de la Régence 58 - 1000 Bruxelas Bélgica España Alexion Pharma Spain Passeig de Gràcia, 85, 4a Planta Barcelona 08008 España Tel 32 02 548 36 36 alexion.belgiumalxn.com

Tel: +34 93 272 30 05
alexion.spain@alxn.com

France Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris France România Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Frana

Tel 33 0 1 53 64 39 50 alexion.francealxn.com Tel 33 0 1 53 64 39 50 alexion.francealxn.com

Slovenija Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Francija Ireland Alexion Pharma UK Unit 14, Horizon Business Village 1, Brooklands Road, Weybridge, Surrey KT13 OTJ UK Tel 33 0 1 53 64 39 50 alexion.francealxn.com Tel 44 0 1 932 35 9220 alexion.ukalxn.com

Alexion Pharma Belgium Rue de la Régence 58 - 1000 Brussel Ísland Belgía Slovenská republika Alexion Pharma France 15 Boulevard de lAmiral Bruix 75016 Paris Francúzsko

Sími 32 02 548 36 36 alexion.belgiumalxn.com Tel 33 0 1 53 64 39 50 alexion.francealxn.com

SuomiFinland Alexion Pharma Belgium Rue de la Régence 58 - 1000 Bryssel Belgien Italia Alexion Pharma Italy S.r.l. Largo Corsia Dei Servi 3 20122 Milano Italia PuhTel 32 02 548 36 36 alexion.belgiumalxn.com Tel 800 915 921 alexion.italyalxn.com

Alexion Pharma Belgium Rue de la Régence 58 - 1000 Sverige Alexion Pharma Belgium Rue de la Régence 58 - 1000 Bryssel Belgia

32 02 548 36 36 alexion.belgiumalxn.com Tel 32 02 548 36 36 alexion.belgiumalxn.com

Alexion Pharma Belgium Rue de la Régence 58 - 1000 Brisele Latvija Beija United Kingdom Alexion Pharma UK Unit 14, Horizon Business Village 1, Brooklands Road, Weybridge, Surrey KT13 OTJ UK Tel 32 02 548 36 36 alexion.belgiumalxn.com Tel 44 0 1 932 35 9220 alexion.ukalxn.com

Lietuva
Alexion Pharma Belgium
Rue de la Régence 58 - 1000 Briuselis
Belgija

Tel: +32 (0)2 548 36 36
alexion.belgium@alxn.com

This leaflet was last approved in .

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Instructions for Use for Healthcare Professionals
Handling Soliris

The following information is intended for medical or healthcare professionals only:

1- How is Soliris supplied?

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

2- Before Administration
Reconstitution and dilution should be performed in accordance with good practices rules, particularly for the respect of asepsis.
Soliris should be prepared for administration by a qualified healthcare professional using aseptic technique.
- Inspect visually Soliris solution for particulate matter and discolouration.
- 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. For 600mg doses, use 60 ml of Soliris (10mg/ml) and add the same volume of diluent. For 900 mg use 90 ml of Soliris and add 90 ml of diluent. The final volume of a 5 mg/ml diluted Soliris solution is 120 ml for 600 mg doses or 180ml for 900 mg doses.
Diluents are 0.9% Sodium chloride, 0.45% Sodium chloride or 5% Dextrose in Water. - Gently agitate the infusion bag containing the diluted Soliris solution to ensure thorough mixing of the medicinal product and diluent.
- The diluted solution should be allowed to warm to room temperature [18°-25° C] prior to administration by exposure to ambient air.
- The diluted solution must not be heated in a microwave or with any heat source other than the prevailing room temperature.
- Discard any unused portion left in a vial as the medicinal product contains no preservatives. - Diluted solution of Soliris may be stored at 2°C -8- C for up to 24 hours prior to administration.

3- Administration
- Do not administer Soliris as an intravenous Push or Bolus Injection.
- Soliris should only be administered via intravenous infusion.
- The diluted solution of Soliris should be administered by intravenous infusion over 25 to 45 minutes via gravity feed, a syringe-type pump, or an infusion pump. It is not necessary to protect the diluted solution of Soliris from light during administration to the patient.
The patient should be monitored for one hour following infusion. If an adverse event occurs during the administration of Soliris, the infusion may be slowed or stopped at the discretion of the physician. If the infusion is slowed, the total infusion time may not exceed two hours.

4- Special Handling and Storage
Soliris vials must be stored in the original carton until time of use under refrigerated conditions at 2-8ºC and protected from light. Do not use beyond the expiration date stamped on the carton.