BEKEMV 300 MG CONCENTRATE FOR INFUSION SOLUTION

Introduction

Package Leaflet: Information for the User

BEKEMV 300 mg concentrate for solution for infusion

eculizumab

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 further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is BEKEMV and what is it used for

What is BEKEMV

The active substance of BEKEMV is eculizumab and it belongs to a group of medicines called monoclonal antibodies. Eculizumab binds to a specific protein in the body that causes inflammation and inhibits it, so that the body's systems cannot attack and destroy vulnerable blood cells or kidneys.

What BEKEMV is used for

Paroxysmal Nocturnal Hemoglobinuria (PNH)

BEKEMV is used to treat adults and children with a specific type of blood disorder called Paroxysmal Nocturnal Hemoglobinuria (PNH). In patients with PNH, red blood cells can be destroyed, which can lead to a reduction in the number of red blood cells (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 its own vulnerable PNH blood cells.

Atypical Hemolytic Uremic Syndrome (aHUS)

BEKEMV is also used to treat patients with a certain type of blood and kidney disorder called Atypical Hemolytic Uremic Syndrome (aHUS). In patients with aHUS, their kidneys and blood cells, including platelets, can be damaged, which can lead to low blood cell counts (thrombocytopenia and anemia), decreased or lost kidney function, blood clots, fatigue, and difficulty functioning normally. Eculizumab can 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 you use BEKEMV

Do not use BEKEMV

• If you are allergic to eculizumab or any of the other ingredients of this medicine (listed in section 6).
• If you have fructose intolerance, a rare genetic disorder in which the enzyme that breaks down fructose is not produced.
• Children under 2 years of age must not receive this medicine, as it contains sorbitol and can be fatal in hereditary fructose intolerance (HFI). It is possible that HFI has not been diagnosed in babies and children under 2 years of age. (See special warnings and precautions for use at the end of this section under the subtitle “BEKEMV contains sorbitol”).
• If you have not been vaccinated against meningococcal infection, unless you are taking antibiotic treatment to reduce the risk of infection until 2 weeks after being vaccinated.
• If you have a meningococcal infection.

Warnings and precautions

Meningococcal infection and other Neisseria infections alert

Treatment with BEKEMV may reduce your natural resistance to infections, especially to certain organisms that cause meningococcal infection (a serious infection of the brain lining and sepsis) and other Neisseria infections, including disseminated gonorrhea.

Consult your doctor before using BEKEMV to ensure that you are vaccinated against Neisseria meningitidis, one of the microorganisms that causes meningococcal infection, at least 2 weeks before starting treatment or that you receive antibiotic treatment to reduce the risk of infection until 2 weeks after being vaccinated.

Make sure you are up to date with your meningococcal vaccinations. You should also be aware that vaccination does not always prevent these types of infections. According to national recommendations, your doctor may consider it necessary to apply additional measures to prevent infection.

If you are at risk of gonorrhea, ask your doctor or pharmacist for information before starting to use this medicine.

Symptoms of meningococcal infection

Given the importance of rapid identification and treatment of certain infections in patients treated with BEKEMV, you will be given a card with a list of specific symptoms of infections to carry with you at all times. It is called the “Patient Safety Card”.

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

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

Treatment of meningococcal infection during travel

If you plan to travel to a remote area where you will not be able to contact your doctor or receive medical treatment for some time, your doctor may take preventive measures, such as prescribing an antibiotic against Neisseria meningitidis for you to take with you. If you experience any of the above symptoms, you should take the prescribed antibiotic. Remember that you must see a doctor as soon as possible, even if you feel better after taking the antibiotic.

Infections

Before using BEKEMV, tell your doctor if you have any infection.

Allergic reactions

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

Children and adolescents

Patients under 18 years of age must be vaccinated against Haemophilus influenzae and pneumococcal infections.

Elderly

No special precautions are required for the treatment of patients aged 65 and over.

Other medicines and BEKEMV

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Women of childbearing age

In women of childbearing age, the use of effective contraceptive methods should be considered during treatment and for up to 5 months after treatment.

Driving and using machines

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

BEKEMV contains sorbitol

This medicine contains 50 mg of sorbitol in each ml.

Sorbitol is a source of fructose. If you (or your child) have hereditary fructose intolerance (HFI), a rare genetic disorder, you must not receive this medicine. Patients with HFI cannot break down fructose, which can cause serious side effects.

Consult your doctor before receiving this medicine if you (or your child) have HFI or cannot take sweet foods or drinks because they cause dizziness, vomiting, or unpleasant effects such as bloating, stomach cramps, or diarrhea.

Sodium

BEKEMV contains sodium when diluted with sodium chloride.

This medicine contains less than 1 mmol of sodium (23 mg) per dose; it is essentially “sodium-free”.

Once diluted with sodium chloride 9 mg/ml (0.9%) solution for injection, this medicine contains 0.34 g of sodium (the main component of table/cooking salt) per 180 ml at the maximum dose. This is equivalent to 17.0% of the maximum recommended daily dietary intake of sodium for an adult. You should take this into account if you are on a controlled sodium diet.

Once diluted with sodium chloride 4.5 mg/ml (0.45%) solution for injection, this medicine contains 0.18 g of sodium (the main component of table/cooking salt) per 180 ml at the maximum dose, which is equivalent to 9.0% of the maximum recommended daily dietary intake of sodium for an adult. You should take this into account if you are on a controlled sodium diet.

If your healthcare professional dilutes the BEKEMV vials with 5% glucose solution, the medicine will be essentially “sodium-free”.

Polysorbate 80

This medicine contains 3.0 mg of polysorbate 80 in each vial (30 ml vial) equivalent to 0.3 mg/kg or less of the maximum dose for adult patients and pediatric patients with a body weight over 10 kg and equivalent to 0.6 mg/kg or less of the maximum dose for pediatric patients with a body weight of 5 to <10 kg. polysorbates can cause allergic reactions. tell your doctor if you or child have any known allergies.< p>

3. How to use BEKEMV

At least 2 weeks before starting treatment with BEKEMV, your doctor will administer a meningococcal vaccine to you if you have not been vaccinated before or if the vaccine you received has expired. If your child is under the age required for vaccination or if you have not been vaccinated at least 2 weeks before starting treatment with BEKEMV, your doctor will prescribe antibiotics to reduce the risk of infection until 2 weeks after being vaccinated.

Your doctor will administer a vaccine to your child under 18 years of age against Haemophilus influenzae and pneumococcal infections according to local vaccination recommendations for each age group.

Instructions for proper use

Your doctor or another healthcare professional will administer the treatment, which consists of the infusion of a diluted BEKEMV vial prepared in a drip bag, through a tube directly into a vein. It is recommended that the first phase of treatment, or initial phase, lasts 4 weeks, after which the maintenance phase will begin:

If you are using this medicine to treat PNH

For adults:

• Initial phase:

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

• Maintenance phase:

• In the fifth week, your doctor will administer an intravenous infusion of diluted BEKEMV corresponding to a dose of 900 mg (3 vials of 30 ml) over 25-45 minutes (35 minutes ± 10 minutes).
• After the fifth week, your doctor will administer 900 mg of diluted BEKEMV every 2 weeks as long-term treatment.

If you are using this medicine to treat aHUS:

For adults:

• Initial phase:

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

• Maintenance phase:

• In the fifth week, your doctor will administer an intravenous infusion of diluted BEKEMV corresponding to a dose of 1200 mg (4 vials of 30 ml) over 25-45 minutes (35 minutes ± 10 minutes).
• After the fifth week, your doctor will administer 1200 mg of diluted BEKEMV every 2 weeks as long-term treatment.

For children and adolescents:

• Children and adolescents with PNH or aHUS and a weight of 40 kg or more will be treated with the adult dose.
• Children and adolescents with PNH or aHUS and a weight under 40 kg require a lower dose based on their weight. Your doctor will calculate it.

In the case of children and adolescents with PNH or aHUS over 2 years of age and under 40 kg:

Patients undergoing plasma exchange may receive additional doses of BEKEMV.

After each infusion, you should remain under observation for one hour and follow your doctor's instructions to the letter.

If you have received more BEKEMV than you should

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

If you miss an appointment to receive BEKEMV

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

If you stop treatment with BEKEMV in PNH

If you stop or discontinue treatment with BEKEMV, it is possible that PNH symptoms may recur more intensely immediately after stopping treatment. Your doctor will discuss the possible side effects with you and explain the risks. Additionally, your doctor will closely monitor you for at least 8 weeks.

The risks of stopping treatment with BEKEMV include an increased destruction of your red blood cells, which can cause:

• a significant decrease in the number of red blood cells (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 stop treatment with BEKEMV in aHUS

If you stop or discontinue treatment with BEKEMV, it is possible that aHUS symptoms may recur. Your doctor will discuss the possible side effects with you and explain the risks. Additionally, your doctor will closely monitor you.

The risks of stopping treatment with BEKEMV include an increased inflammatory process of your platelets, which can cause:

• a significant decrease in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of your 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.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them. Your doctor will discuss the possible adverse effects and explain the benefits and risks of BEKEMV before starting treatment.

The most serious adverse effect was meningococcal sepsis. If you experience any symptoms of a meningococcal infection (see section 2 "Meningococcal Infection and Other Neisseria Infections Alert"), inform your doctor immediately.

If you are unsure about 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)

• pneumonia (lung infection), cold (nasopharyngitis), urinary tract infection (urinary infection)
• low white blood cell count (leucopenia), reduction of red blood cells that can cause paleness and weakness or shortness of breath
• insomnia
• dizziness, high blood pressure
• upper respiratory tract infection, cough, sore throat (oropharyngeal pain), bronchitis, fever (herpes simplex)
• diarrhea, vomiting, nausea, abdominal pain, rash, hair loss (alopecia), itching (pruritus)
• joint pain (arms and legs), pain in the limbs (arms and legs)
• fever (pyrexia), feeling of fatigue (fatigue), flu-like illness
• infusion-related reaction

Uncommon(may affect up to 1 in 100 patients)

• severe infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, gastroenteritis, cystitis
• infection, fungal infection, pus accumulation (abscesses), skin infection (cellulitis), flu, sinusitis, dental infection (abscess), gum infection
• relatively low platelet count (thrombocytopenia), low lymphocyte count (a specific type of white blood cell) (lymphopenia), feeling 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 a part of the body (paresthesia), tremors, taste disorder (dysgeusia), fainting
• blurred vision
• ringing in the ears, vertigo
• sudden and rapid development of extremely high blood pressure, low blood pressure, hot flashes, venous disorders
• shortness of breath (dyspnea), nosebleeds, stuffy nose (nasal congestion), throat irritation, nasal discharge (rhinorrhea)
• peritoneal inflammation (tissue that lines most abdominal organs), constipation, stomach discomfort after eating (dyspepsia), abdominal distension
• hives, skin redness, dry skin, red or purple spots on the skin, increased sweating, skin inflammation
• muscle cramps, 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
• increased liver enzymes, decreased proportion of blood volume occupied by red blood cells, decreased 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
• red blood cell destruction (hemolysis), cellular aggregation, abnormal coagulation factor, abnormal coagulation
• disease with hyperactive thyroid (Graves' disease)
• abnormal dreams
• eye irritation
• bruises
• unusual gastric reflux of food, gum pain
• yellowing of the skin and/or eyes (jaundice)
• skin color disorders
• muscle spasms in the mouth, joint swelling
• menstrual disorder
• abnormal sensation at the infusion site, feeling of heat

Reporting Adverse Effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of BEKEMV

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date stated on the packaging and on the label of the vial after "EXP". The expiration date is the last day of the month indicated.

Store in a refrigerator (between 2°C and 8°C). Do not freeze.

BEKEMV vials can be stored in the original packaging outside the refrigerator for a single period of up to 7days. At the end of this period, the product can be returned to the refrigerator.

Store in the original packaging to protect from light. After dilution, the medicine must be used within 24 hours.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package Contents and Additional Information

Composition of BEKEMV

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

• Other components are:
• acetic acid
• sodium hydroxide
• edetic acid (EDTA)
• sorbitol (E 420), see section 2 "BEKEMV contains sorbitol"
• polysorbate 80
• water for injectable preparations

BEKEMV contains sodium and polysorbate 80. See section 2.

Appearance of the Product and Package Contents

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

BEKEMV is a clear to opalescent and colorless to slightly yellowish solution.

Marketing Authorization Holder and Manufacturer

Amgen Technology (Ireland) UC

Pottery Road, Dun Laoghaire

Co. Dublin,

A96 F2A8 Ireland

Marketing Authorization Holder

Amgen Technology (Ireland) UC

Pottery Road, Dun Laoghaire

Co. Dublin,

A96 F2A8 Ireland

Manufacturer

Amgen NV

Telecomlaan 5-7

1831 Diegem

Belgium

You can request more information about this medicine from the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet

Other Sources of Information

Detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

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Instructions for Healthcare Professionals on the Handling of BEKEMV

In order to improve the traceability of biological medicines, the name and batch number of the administered medicine should be clearly recorded.

This information is intended for healthcare professionals only.

1. How is BEKEMV Supplied?

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

1. Before Administering the Medicine

Dilution must be performed in accordance with good practice standards, especially with regard to asepsis.

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

• Visually inspect the BEKEMV solution to ensure it does not contain particles or color changes.
• Withdraw the required amount of BEKEMV from the vial or vials using a sterile syringe.
• Transfer the recommended dose to an infusion bag.
• Dilute BEKEMV 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 dose of 300 mg, use 30 ml of BEKEMV (10 mg/ml) and add 30 ml of diluent.
  • For a dose of 600 mg, use 60 ml of BEKEMV and add 60 ml of diluent.
  • For a dose of 900 mg, use 90 ml of BEKEMV and add 90 ml of diluent.
  • For a dose of 1200 mg, use 120 ml of BEKEMV and add 120 ml of diluent.

The final volume of a diluted BEKEMV solution of 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 1200 mg doses.

• The diluents that can be used are sodium chloride 9 mg/ml (0.9%) solution for injection, sodium chloride 4.5 mg/ml (0.45%) solution for injection, or glucose solution 5% in water.

• Gently shake the infusion bag with the diluted BEKEMV solution to ensure the medicine and diluent are well mixed.
• Allow the diluted solution to reach room temperature (between 18°C - 25°C) before administration, leaving it at room temperature.
• The diluted solution must not be heated in a microwave or other heat source other than room temperature.
• Discard any remaining medicine in the vial.
• The diluted BEKEMV solution can be stored between 2°C and 8°C for up to 24 hours before administration.

1. Administration

• Do not administer BEKEMV by direct intravenous injection or by bolus injection.
• BEKEMV should only be administered by intravenous infusion.
• The diluted BEKEMV solution should be administered by intravenous infusion over 25 to 45 minutes (35 minutes ± 10 minutes) in adults and 1 to 4 hours in pediatric patients under 18 years of age by gravity drip, syringe pump, or infusion pump. It is not necessary to protect the diluted BEKEMV solution from light during administration to the patient.

The patient should be monitored for one hour after infusion. If an adverse effect occurs during BEKEMV administration, the infusion may be interrupted or the rate reduced, according to the doctor's judgment. If the rate is reduced, the total duration of the infusion should not exceed two hours in adults and not more than four hours in pediatric patients under 18 years of age.

1. Special Storage and Handling Conditions

Store in a refrigerator (between 2°C and 8°C). Do not freeze. Store in the original packaging to protect from light. BEKEMV vials can be stored in the original packaging outside the refrigerator for a single period of up to 7days. At the end of this period, the product can be returned to the refrigerator.

Do not use BEKEMV after the expiration date stated on the packaging and on the label of the vial after "EXP". The expiration date is the last day of the month indicated.