Package Insert: Information for the User

BEKEMV 300 mg Concentrate for Solution for Infusion

Eculizumab

Read this package insert carefully before you start using this medicine, because it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

What is BEKEMV

The active ingredient of BEKEMV is eculizumab and it belongs to a group of medications 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 is BEKEMV used for

Paroxysmal nocturnal hemoglobinuria

BEKEMV is used in the treatment of adults and children with a specific type of blood system disease called paroxysmal nocturnal hemoglobinuria (PNH). In patients with PNH, red blood cells can be destroyed, leading to a reduction in the number of red blood cells (anemia), fatigue, functional difficulty, pain, dark 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

BEKEMV is also used for the treatment of adult and pediatric patients with a certain type of circulatory and renal disease called atypical hemolytic uremic syndrome (aHUS). In patients with aHUS, their kidneys and blood cells, including platelets, may be damaged, leading to low blood counts (thrombocytopenia and anemia), decreased or lost renal 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 renal cells.

No use BEKEMV

• If you are allergic to eculizumab or any of the other components of this medication (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 should not receive this medication, as it contains sorbitol and may be fatal in hereditary fructose intolerance (HFI). It is possible that HFI has not yet been diagnosed in infants and children under 2 years of age. (See special warnings at the end of this section under the subtitle “BEKEMV contains sorbitol”).
• If you have not been vaccinated against meningococcal infection, unless you have received 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 infections byNeisseria

Treatment with BEKEMV may reduce your natural resistance to infections, especially certain organisms that cause meningococcal infection (severe brain and sepsis) and other infections byNeisseria, including disseminated gonorrhea.

Consult your doctor before using BEKEMV to ensure that you are vaccinated againstNeisseria meningitidis, one of the microorganisms that produces meningococcal infection, at least 2 weeksbefore 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 on your meningococcal vaccinations. Also, note that vaccination does not always prevent this type of infection. According to national recommendations, your doctor may consider it necessary to apply additional measures to prevent infection.

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

Symptoms of meningococcal infection

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

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

• bothersome headache accompanied by nausea or vomiting
• bothersome headache accompanied by stiffness of the neck or back
• fever
• eruption
• confusion
• intense 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 againstNeisseria meningitidisfor you to carry with you. If you experience any of the symptoms mentioned above, 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, inform your doctor if you have any infections.

Allergic reactions

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

Children and adolescents

Patients under 18 years of age should be vaccinated againstHaemophilus influenzaeand pneumococcal infections.

Older adults

No special precautions are necessary for the treatment of patients aged 65 years and older.

Other medications and BEKEMV

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.

Pregnancy, breastfeeding, and fertility

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

Women of childbearing age

Consider the use of effective contraceptive methods during treatment and for up to 5 months after treatment.

Driving and operating machinery

BEKEMV has no or negligible influence on the ability to drive and operate machinery.

BEKEMV contains sorbitol

This medication contains 50 mg of sorbitol per ml.

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

Consult your doctor before receiving this medication 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 medication contains less than 1 mmol of sodium (23 mg) per dose; that is, it is essentially “sodium-free”.

Once diluted with 0.9% sodium chloride solution for injection, this medication contains 0.34 g of sodium (main component of table salt/for cooking) per 180 ml at the maximum dose. This is equivalent to 17.0% of the maximum daily sodium intake recommended in the diet for an adult. You should be aware of this if you follow a sodium-controlled diet.

Once diluted with 0.45% sodium chloride solution for injection, this medication contains 0.18 g of sodium (main component of table salt/for cooking) per 180 ml at the maximum dose, which is equivalent to 9.0% of the maximum daily sodium intake recommended in the diet for an adult. You should be aware of this if you follow a sodium-controlled diet.

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

At least 2 weeks before starting treatment with BEKEMV, your doctor will administer a vaccine against meningococcal infection if you have not been vaccinated previously or if the vaccine administered to you has expired. If your child is under the required age 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 old againstHaemophilus influenzaeand pneumococcal infections in accordance with local vaccination recommendations for each age range.

Instructions for proper use

Your doctor or another healthcare professional will administer the treatment, which will consist of infusing a solution from the BEKEMV vial prepared in a drip bag, directly into a vein through a catheter. It is recommended that the first phase of treatment, or initial phase, last 4 weeks, after which the maintenance phase will begin:

If you use this medication to treat HPN

For adults:

• Initial phase:

During the first 4 weeks, your doctor will administer an intravenous infusion of BEKEMV diluted every week. Each administration 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 5th week, your doctor will administer an intravenous infusion of BEKEMV diluted corresponding to a dose of 900 mg (3 vials of 30 ml) for 25-45 minutes (35 minutes ± 10 minutes).
• After the 5th week, your doctor will administer 900 mg of BEKEMV diluted every 2 weeks as long-term treatment.

If you use this medication to treat SHUa:

For adults:

• Initial phase:

During the first 4 weeks, your doctor will administer an intravenous infusion of BEKEMV diluted every week. Each administration will consist of a dose of up to 900 mg (3 vials of 30 ml) and will last 25 to 45 minutes (35 minutes ± 10 minutes).

• Maintenance phase:

• In the 5th week, your doctor will administer an intravenous infusion of BEKEMV diluted corresponding to a dose of up to 1200 mg (4 vials of 30 ml) for 25-45 minutes (35 minutes ± 10 minutes).
• After the 5th week, your doctor will administer a dose of up to 1200 mg of BEKEMV diluted every 2 weeks as long-term treatment.

For children and adolescents:

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

In the case of children and adolescents with HPN or SHUa over 2 years of age and with a weight of less than 40 kg:

Patients undergoing plasma exchange may receive additional doses of BEKEMV.

After each infusion, you must remain under observation for 1 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 been accidentally administered a dose of BEKEMV greater than the prescribed dose, consult your doctor.

If you forget to attend an appointment to receive BEKEMV

If you forget to attend an appointment, consult your doctor immediately and read the section “If you interrupt treatment with BEKEMV”.

If you interrupt treatment with BEKEMV in HPN

If you interrupt or discontinue treatment with BEKEMV, it is possible that HPN symptoms will reappear more intensely just after interrupting treatment. If you interrupt treatment with BEKEMV, your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you for at least 8 weeks.

The risks of interrupting treatment with BEKEMV include an increase in the destruction of your red blood cells, which may produce the following:

• a significant decrease in the number of red blood cells (anemia);
• confusion or lack of attention;
• chest pain or angina;
• an increase in serum creatinine concentration (kidney problems); or
• thrombosis (blood clots).

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

If you interrupt treatment with BEKEMV in SHUa

If you interrupt or discontinue treatment with BEKEMV, it is possible that SHUa symptoms will reappear. Your doctor will discuss possible side effects and explain the risks. Additionally, they will closely monitor you.

The risks of interrupting treatment with BEKEMV include an increase in the inflammatory processes of your platelets, which may produce the following:

• a significant decrease in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of your red blood cells;
• decreased urination (kidney problems);
• an increase in 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.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Your doctor will inform you about the possible side effects and explain the benefits and risks of BEKEMV before starting treatment.

The most serious side effect was meningococcal sepsis. If you experience any of the symptoms of meningococcal infection (see section 2 “Meningococcal infection alert and other Neisseria infections”), inform your doctor immediately.

If you are unsure about the side 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 10patients)

• lung infection (pneumonia), common cold (nasopharyngitis), urinary tract infection (urinary tract infection)
• low white blood cell count (leucopenia), reduction of red blood cells that can cause paleness and cause 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 extremities (arms and legs)
• fever (pyrexia), feeling of fatigue (fatigue), flu-like illness
• reaction related to perfusion

Uncommon(may affect up to 1 in 100patients)

• serious infection (meningococcal infection), sepsis, septic shock, viral infection, lower respiratory tract infection, stomach flu (gastrointestinal infection), 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,disturbance of taste (dysgeusia), dizziness
• 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), nasal bleeding, nasal congestion (congestion), throat irritation, nasal secretion (rhinorrhea)
• inflammation of the peritoneum (tissue that covers most of the abdominal organs), constipation, postprandial abdominal discomfort (dyspepsia), abdominal distension
• urticaria, skin redness or rashes, skin dryness, red or purple spots on the skin, increased sweating,skin inflammation
• muscle cramps, muscle pain, back pain and neck pain, bone pain
• renal disorders, difficulty or pain urinating (dysuria), blood in urine
• spontaneous erection
• swelling (edema), chest discomfort, feeling of weakness (asthenia), chest pain, pain at the perfusion site, chills
• increase in liver enzymes, decrease in the proportion of blood volume occupied by red blood cells, decrease in the protein that transports oxygen in red blood cells

Rare(may affect up to 1 in 10,000patients)

• fungal infection (Aspergillus infection), joint infection (bacterial arthritis), Haemophilus influenzae infection, impetigo, sexually transmitted bacterial disease (gonorrhea)
• skin tumor (melanoma), bone marrow disorder
• destruction of red blood cells (hemolysis), cellular aggregation, abnormal coagulation factor, abnormal coagulation
• hyperthyroidism (Basedow's disease)
• abnormal dreams
• eye irritation
• bruising
• unusual reflux of food, gum pain
• yellow discoloration of the skin and/or eyes (jaundice)
• skin color disorders
• muscle spasms of the oral musculature,joint swelling
• menstrual disorder
• abnormal release of the medication from the vein, abnormal sensation at the perfusion site, feeling of heat

Reporting of side effects

If you experience any type of side effect, consult your doctor, pharmacist or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendix V.By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the packaging and on the vial label after “CAD”. The expiration date is the last day of the month indicated.

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

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

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

Medicines should not be thrown away through the drains. Ask your pharmacist how to dispose of the packaging and the medications that you no longer need. In this way, you will help protect the environment.

Composition of BEKEMV

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

• The other components are:
• • acetic acid
  • sodium hydroxide
  • ethylenediaminetetraacetic acid (EDTA)
  • sorbitol (E 420), see section 2 “BEKEMV contains sorbitol”
  • polysorbate 80
  • water for injection

Appearance of the product and contents of the pack

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

BEKEMV is a transparent to opalescent and colourless to slightly yellowish solution.

Holder of the marketing authorisation and responsible person for the manufacture

Amgen Technology (Ireland) UC

Pottery Road, Dun Laoghaire

Co. Dublin,

A96 F2A8 Ireland

You can request more information about this medicine by contacting the local representative of the marketing authorisation holder:

Last update date of this leafletof this leaflet

Other sources of information

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

Instructions for use 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 must be clearly recorded.

This information is intended only for healthcare professionals.

1. How is BEKEMV supplied?

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

1. Before administering the medicine

The dilution must be carried out in accordance with good practices, especially in terms of asepsis.

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

• Visually inspect the BEKEMV solution to check that it does not contain particles or colour changes.
• Extract 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 5mg/ml (initial concentration divided by 2) by adding the appropriate amount of solvent to the infusion bag.
• • To prepare a dose of 300mg, use 30ml of BEKEMV (10mg/ml) and add 30ml of solvent.
  • To doses of 600mg, use 60ml of BEKEMV and add the same volume of solvent.
  • To a dose of 900mg, use 90ml of BEKEMV and add 90ml of solvent.
  • To a dose of 1200mg use 120ml of BEKEMV and add 120ml of solvent.

The final volume of a diluted BEKEMV solution of 5mg/ml is 60ml for doses of 300mg, 120ml for doses of 600mg and 180ml for doses of 900mg or 240ml for doses of 1200mg.

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

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

1. Administration

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

The patient will be monitored for 1 hour after infusion. If an adverse effect occurs during the administration of BEKEMV, the infusion should be interrupted or the rate reduced, as decided by the doctor. If the rate is reduced, the total duration of the infusion cannot exceed 2 hours in adults and not more than 4hours in paediatric patients under 18years of age.

1. Special storage and handling conditions

Store in the refrigerator (between 2°C and 8°C). Do not freeze. Store in the original packaging to protect it from light. The BEKEMV vials can be stored 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 expiry date that appears on the packaging and on the vial label after “CAD”. The expiry date is the last day of the month indicated.