Bekemv

Package leaflet: Information for the user

BEKEMV 300 mg concentrate for solution for infusion

eculizumab
This medicinal product is subject to additional monitoring. This will allow for rapid identification of new safety information. You can help by reporting any side effects you experience while taking this medicine. See the end of section 4 for information on how to report side effects.
Please read all of this leaflet carefully before 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 others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet

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

1. What BEKEMV is and what it is used for

What BEKEMV is
BEKEMV contains the active substance eculizumab and belongs to a class of medicines called 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 or the kidneys.

What BEKEMV is used for

Paroxysmal nocturnal haemoglobinuria
BEKEMV is used to treat adults and children 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-coloured urine, dyspnoea (difficulty breathing), and blood clots. Eculizumab can block the body's inflammatory response and its ability to attack and destroy its own vulnerable red blood cells in PNH.

Atypical haemolytic uremic syndrome
BEKEMV is also used to treat adult and paediatric patients with a disease affecting the blood and renal system called atypical haemolytic uremic syndrome (aHUS). In patients with aHUS, the kidneys, red blood cells, and platelets may become inflamed; this leads to low platelet and red blood cell counts (thrombocytopenia and anaemia), reduced or loss of 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 its own vulnerable blood and kidney cells.

2. What you need to know before using BEKEMV

Do not use BEKEMV

• if you are allergic to eculizumab or to any of the other ingredients of this medicine (listed in section 6);
• if you have fructose intolerance, a rare genetic disease in which the enzyme responsible for metabolizing fructose is not produced;
• this medicine must not be administered to children under 2 years of age. This medicine contains sorbitol, and sorbitol may be fatal in the case of hereditary fructose intolerance (HFI). In children under 2 years of age, HFI may not yet have been diagnosed. (See special warnings at the end of this section under “BEKEMV contains sorbitol”);
• if you have not been vaccinated against meningococcal infection or if you are not taking antibiotics to reduce the risk of infection for two weeks after vaccination;
• if you currently have a meningococcal infection.

Warnings and precautions
Alert on meningococcal infection and other Neisseria infections
Treatment with BEKEMV may reduce your natural resistance to infections, particularly against certain microorganisms causing meningococcal infection (a serious infection of the lining of the brain and sepsis) and other Neisseria infections, including disseminated gonorrhea.
Before starting BEKEMV, speak with your doctor to ensure you are vaccinated against Neisseria meningitidis, an organism that causes meningococcal infection, at least 2 weeks prior to starting treatment, or that you take antibiotics to reduce the risk of infection for two weeks after vaccination.
Make sure 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 using this medicine.

Symptoms of meningococcal infection
Because it is important to rapidly identify and treat certain types of infection in patients treated with BEKEMV, you will be given a card to carry with you listing specific symptoms to watch for. This card is called the “Patient Safety 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;
• rash;
• confusion;
• severe muscle pain with flu-like symptoms;
• sensitivity to light.

Treatment of meningococcal infection while travelling
If you plan to travel to a remote country where you may not be able to contact a doctor or where immediate medical treatment may not be available, 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 BEKEMV, inform your doctor if you currently have any infections.

Allergic reactions
BEKEMV 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 patients over 65 years of age.

Other medicines and BEKEMV
Inform your doctor or pharmacist if you are currently using, have recently used, or might use any other medicines.

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

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

BEKEMV contains sorbitol
This medicine contains 50 mg of sorbitol per mL.
Sorbitol is a source of fructose. If your doctor has diagnosed you (or the child) with hereditary fructose intolerance (HFI), a rare genetic disorder, you (or the child) must not take this medicine. Patients with HFI are unable to metabolize fructose, and its accumulation can lead to serious adverse effects.
Before taking this medicine, inform your doctor if you (or the child) have hereditary fructose intolerance or if the child feels unwell, vomits, or experiences unpleasant reactions such as bloating, stomach cramps, or diarrhea after consuming sweetened foods or drinks.

Sodium
BEKEMV contains sodium when diluted with sodium chloride.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free.”
Once diluted with 9 mg/mL (0.9%) sodium chloride injection solution, this medicine contains 0.34 g of sodium (the main component of table salt) per 180 mL at the maximum dose.
This corresponds to 17.0% of the maximum daily sodium intake recommended in an adult’s diet. This should be taken into account if you are on a low-sodium diet.
Once diluted with 4.5 mg/mL (0.45%) sodium chloride injection solution, this medicine contains 0.18 g of sodium per 180 mL at the maximum dose.
This corresponds to 9.0% of the maximum daily sodium intake recommended in an adult’s diet. This should be taken into account if you are on a low-sodium diet.
If the healthcare provider dilutes BEKEMV vials with 5% glucose solution, the medicine is essentially “sodium-free.”

3. How to use BEKEMV

At least two weeks before starting treatment with BEKEMV, your doctor will administer a vaccine against meningococcal infection, if the vaccine has not already been given previously or if your vaccination is no longer up to date. If your child is not yet of an age eligible for vaccination or if you have not been vaccinated at least two weeks prior to starting treatment with BEKEMV, your doctor will prescribe antibiotics to reduce the risk of infection for up to two weeks after vaccination.
Your doctor will administer a vaccine against Haemophilus influenzae and pneumococcal infections to your child under 18 years of age, according to national vaccination recommendations for each age group.

Instructions for correct administration

This treatment will be administered by your doctor or another healthcare professional as an intravenous infusion of a diluted solution from a BEKEMV vial directly into a vein. It is recommended that treatment begins with an initial phase lasting four weeks, followed by a maintenance phase.

If you are using this medicine to treat EPN:
For adults:

• Initial phase

Once weekly for the first four weeks, your doctor will administer an intravenous infusion of a diluted solution of BEKEMV. Each infusion will consist of a 600 mg dose (2 vials of 30 mL) and will last 25–45 minutes (35 minutes ± 10 minutes).

• Maintenance phase
  • In week five, your doctor will administer an intravenous infusion of a diluted solution of BEKEMV at a dose of 900 mg (3 vials of 30 mL) over a period of 25–45 minutes (35 minutes ± 10 minutes).
  • From week five onwards, your doctor will administer 900 mg of diluted BEKEMV solution every two weeks as long-term therapy.

If you are using this medicine to treat SEUa:
For adults:

• Initial phase

Once weekly for the first four weeks, your doctor will administer an intravenous infusion of a diluted solution of BEKEMV. Each infusion will consist of a 900 mg dose (3 vials of 30 mL) and will last 25–45 minutes (35 minutes ± 10 minutes).

• Maintenance phase
  • In week five, your doctor will administer an intravenous infusion of a diluted solution of BEKEMV at a dose of 1,200 mg (4 vials of 30 mL) over a period of 25–45 minutes (35 minutes ± 10 minutes).
  • From week five onwards, your doctor will administer 1,200 mg of diluted BEKEMV solution every two weeks as long-term therapy.

For children and adolescents:

• Children and adolescents with EPN or SEUa who weigh 40 kg or more will receive the same dosage as adults.
• Children and adolescents with EPN or SEUa 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 with EPN or SEUa aged over 2 years and weighing less than 40 kg:

Patients undergoing plasma exchange may receive an additional dose of
BEKEMV.
After each infusion, you will be monitored for approximately one hour. You must carefully follow your doctor's instructions.
If you receive more BEKEMV than you should
If you suspect that you have received a higher dose of BEKEMV than prescribed, consult your doctor immediately.
If you miss an appointment for BEKEMV administration
If you miss an appointment, contact your doctor immediately and refer to the next section “If you interrupt treatment with BEKEMV”.
If you interrupt treatment with BEKEMV for aHUS
Interrupting or stopping treatment with BEKEMV may rapidly lead to a recurrence of aHUS symptoms in a more severe form. Your doctor will discuss the possible side effects with you and explain the risks. Your doctor will closely monitor you for at least 8 weeks.
The risks of discontinuing BEKEMV include increased destruction of red blood cells, which may cause:

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

If you interrupt treatment with BEKEMV for STEC-HUS
Interrupting or stopping treatment with BEKEMV may lead to a recurrence of STEC-HUS symptoms. Your doctor will discuss possible side effects with you and explain the risks. Your doctor will closely monitor you.
The risks of discontinuing BEKEMV include increased platelet inflammation, which may cause:

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

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them. Before treatment, your doctor will discuss with you the possible side effects and explain the benefits and risks of BEKEMV.
The most serious side effect observed 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 clarification.

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 infections (urinary tract infection)
• low white blood cell count (leucopenia), reduced red blood cells which may cause pale skin, weakness or shortness of breath
• inability to sleep
• dizziness, high blood pressure
• upper respiratory tract infections, 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 reaction

Uncommon (may affect up to 1 in 100 people)

• serious infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, gastrointestinal flu (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 lymphocyte levels, low levels of a particular type of white blood cell (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 sensation in part of the body (paraesthesia), tremor, taste disturbance (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
• urticaria, skin redness, dry skin, red or purple spots under the skin, increased sweating, skin inflammation
• muscle cramps, 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

Rare (may affect up to 1 in 1,000 people)

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus influenzae 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
• 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
• muscle spasms of the mouth, joint swelling
• menstrual disorders
• abnormal leakage of infused drug outside the vein, abnormal sensation at infusion site, feeling of warmth

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse. You can also report side effects directly through 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 BEKEMV

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.
The vials of BEKEMV in the original packaging may be removed from the refrigerator only once for a maximum of 7 days.
At the end of this period, the product must not be returned to the refrigerator.
Keep in the original packaging to protect the medicine from light. After dilution, use the medicine within 24 hours.
Do not dispose of medicines 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 BEKEMV contains

• The active substance is eculizumab (300 mg/30 mL in a vial at 10 mg/mL).
• The other components are:
• acetic acid
• sodium hydroxide
• disodium edetate (EDTA)
• sorbitol (E420, see section 2 “BEKEMV contains sorbitol”)
• polysorbate 80
• water for injections

Description of the appearance of BEKEMV and contents of the pack
BEKEMV is a concentrate for solution for infusion (30 mL in a vial – pack of 1 vial).
BEKEMV is a solution that ranges from clear to opalescent and from colourless to slightly yellow.

Marketing Authorisation Holder and Manufacturer
Amgen Technology (Ireland) UC
Pottery Road, Dun Laoghaire
Co. Dublin,
A96 F2A8 Ireland

Marketing Authorisation Holder
Amgen Technology (Ireland) UC
Pottery Road, Dun Laoghaire
Co. Dublin,
A96 F2A8 Ireland

Manufacturer
Amgen NV
Telecomlaan 5-7
1831 Diegem
Belgium

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

België/Belgique/Belgien          Lietuva
s.a. Amgen n.v.               Amgen Switzerland AG Vilniaus filialas
Tél/Tel: +32 (0)2 7752711          Tel: +370 5 219 7474

България                 Luxembourg/Luxemburg
Амджен България ЕООД         s.a. Amgen
Тел.: +359 (0)2 424 7440          Belgique/Belgien
                          Tél/Tel: +32 (0)2 7752711

Česká republika            Magyarország
Amgen s.r.o.                 Amgen Kft.
Tel: +420 221 773 500           Tel.: +36 1 35 44 700

Danmark                  Malta
Amgen, filial af Amgen AB, Sverige    Amgen S.r.l.
Tlf: +45 39617500              Italy
                          Tel: +39 02 6241121

Deutschland               Nederland
Amgen GmbH                 Amgen B.V.
Tel: +49 89 1490960             Tel: +31 (0)76 5732500

Eesti                    Norge
Amgen Switzerland AG Vilniaus filialas  Amgen AB
Tel: +372 586 09553             Tlf: +47 23308000

Ελλάδα                  Österreich
Amgen Ελλάς Φαρμακευτικά Ε.Π.Ε.    Amgen GmbH
Τηλ: +30 210 3447000            Tel: +43 (0)1 50 217

España                  Polska
Amgen S.A.                  Amgen Biotechnologia Sp. z o.o.
Tel: +34 93 600 18 60            Tel.: +48 22 581 3000

France                  Portugal
Amgen S.A.S.                 Amgen Biofarmacêutica, Lda.
Tél: +33 (0)9 69 363 363          Tel: +351 21 422 06 06

Hrvatska                 România
Amgen d.o.o.                Amgen România SRL
Tel: +385 (0)1 562 57 20          Tel: +4021 527 3000

Ireland                  Slovenija
Amgen Ireland Limited           AMGEN zdravila d.o.o.
Tel: +353 1 8527400            Tel: +386 (0)1 585 1767

Ísland                   Slovenská republika
Vistor hf.                   Amgen Slovakia s.r.o.
Sími: +354 535 7000            Tel: +421 2 321 114 49

Italia                   Suomi/Finland
Amgen S.r.l.                  Amgen AB, sivuliike Suomessa/Amgen AB, filial
Tel: +39 02 6241121             i Finland
Puh/Tel: +358 (0)9 54900500

Kύπρος                   Sverige
C.A. Papaellinas Ltd            Amgen AB
Τηλ: +357 22741 741            Tel: +46 (0)8 6951100

Latvija                   United Kingdom (Northern Ireland)
Amgen Switzerland AG Rīgas filiāle   Amgen Limited
Tel: +371 257 25888             Tel: +44 (0)1223 420305

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/

Instructions for use for healthcare professionals – Handling of BEKEMV
To improve the traceability of biological medicinal products, the name and batch number of the administered product must be clearly recorded.
The following information is intended exclusively for healthcare professionals:

1. How is BEKEMV supplied?

Each BEKEMV vial contains 300 mg of active substance in 30 mL of solution.

2. Before administration

Dilution must be performed in accordance with good preparation practices, particularly maintaining aseptic conditions.
BEKEMV must be prepared for administration by a qualified healthcare professional using an aseptic technique.

• Visually inspect the BEKEMV solution to ensure it is free from particulate matter and discoloration.
• Withdraw the required amount of BEKEMV from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute BEKEMV to a final concentration of 5 mg/mL (initial concentration halved) by adding the appropriate volume of diluent to the infusion bag.
  • For 300 mg doses, use 30 mL of BEKEMV (10 mg/mL) and add 30 mL of diluent.
  • For 600 mg doses, use 60 mL of BEKEMV and add 60 mL of diluent.
  • For 900 mg doses, use 90 mL of BEKEMV and add 90 mL of diluent.
  • For 1,200 mg doses, use 120 mL of BEKEMV and add 120 mL of diluent. The final volume of the diluted BEKEMV solution at 5 mg/mL will be 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.
• Acceptable diluents are sodium chloride 9 mg/mL (0.9%) solution for injection, sodium chloride 4.5 mg/mL (0.45%) solution for injection, or glucose 5% in water.
• Gently mix the infusion bag containing the diluted BEKEMV solution to ensure thorough mixing of drug and diluent.
• The diluted solution should be allowed 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 other than room temperature.
• Discard any unused portion remaining in the vial.
• Diluted BEKEMV solutions may be stored at 2°C - 8°C for up to 24 hours prior to administration.

3. Administration

• Do not administer BEKEMV as rapid intravenous injections or bolus injections.
• BEKEMV must be administered only by intravenous infusion.
• The diluted BEKEMV solution should be administered as an intravenous infusion lasting 25–45 minutes (35 minutes ± 10 minutes) in adult patients, and as an infusion lasting 1–4 hours in pediatric patients under 18 years of age, using an intravenous drip set, syringe pump, or infusion pump. The diluted BEKEMV 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 BEKEMV 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 the refrigerator (2°C – 8°C). Do not freeze. Keep in the original packaging to protect the medicine from light. BEKEMV vials in the original packaging may be removed from the refrigerator only once for a maximum of 7 days. At the end of this period, the product may not be returned to the refrigerator.
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.