EPYSQLI 300 мг Концентрат для инфузионного раствора

Содержание инструкции

1. Epysqli 300 mg concentrate for solution for infusion
   1. What is Epysqli and what is it used for
   2. What you need to know before you use Epysqli
   3. How to use Epysqli
   4. Possible side effects
   5. How to store Epysqli
   6. Package Contents and Other Information

Epysqli 300 mg concentrate for solution for infusion

eculizumab
Medicinal product subject to additional monitoring. This will allow the rapid identification of
new safety information. You can contribute by reporting any adverse effects
experienced during the use of this medicine. See the end of section 4 for
information on how to report adverse effects.

Read this leaflet carefully before using this medicine as 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 pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet

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

1. What is Epysqli and what is it used for

What is Epysqli
Epysqli contains the active substance eculizumab and belongs to a class of medicines called
monoclonal antibodies. Eculizumab binds to a specific protein present in the body, which causes
inflammation, and inhibits its action, thus preventing specific systems of the body
from attacking and destroying vulnerable blood cells, kidneys, muscles or optic nerves and the
spinal cord.

What is Epysqli used for
Paroxysmal nocturnal hemoglobinuria
Epysqli is used to treat adult and pediatric patients with a disease affecting the
blood, called paroxysmal nocturnal hemoglobinuria (PNH). In patients with PNH, red
blood cells can be destroyed; this causes a decrease in the number of red blood cells (anemia),
fatigue, functional limitations, pain, dark urine, dyspnea (difficulty breathing) and blood
clots. Eculizumab can block the body's inflammatory response and its ability to
attack and destroy its own vulnerable PNH red blood cells.

Atypical hemolytic uremic syndrome
Epysqli is also used for the treatment of adult and pediatric patients with a disease that
affects the blood and the renal system called atypical hemolytic uremic syndrome (aHUS). In
patients with aHUS, the kidneys, red blood cells and platelets can become inflamed; this causes
a decrease in platelets and red blood cells (thrombocytopenia and anemia), reduced or loss of
renal function, blood clots, fatigue and functional limitations. 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 you use Epysqli

Do not use Epysqli

• if you are allergic to eculizumab, to proteins derived from mouse 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 (or if you are not taking antibiotics to reduce the risk of infection for two weeks after being vaccinated);
• if you have a meningococcal infection.

Warnings and precautions
Alert regarding meningococcal infection and other infections caused byNeisseria
Therapy with Epysqli may reduce natural resistance to infections, especially against
some microorganisms that cause meningococcal infection (severe infection of the lining of the
brain and sepsis) and other infections caused by Neisseria,including disseminated gonorrhea.
Talk to your doctor before taking Epysqli to make sure you have been vaccinated against

Neisseria meningitidis, an organism that causes meningococcal infection, at least 2 weeks before
starting treatment or taking antibiotics to reduce the risk of infection for two weeks
after being vaccinated. Make sure your vaccination against meningococcal infection is not
expired. You should know, however, that vaccination may not prevent this type of infection. In
accordance with national recommendations, your doctor may deem it necessary to adopt
additional measures to prevent infection.
If you are at risk of gonorrhea, ask your doctor or pharmacist for advice before taking this
medicine.
Symptoms of meningococcal infection
Given the importance of identifying and treating certain types of infection quickly in patients treated with
Epysqli, you will be given a card to carry with you listing specific symptoms to watch out for.
This card is called: “Patient Safety Card”.
If you experience any of the following symptoms, you should immediately call your doctor:

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

Treatment of meningococcal infection while traveling
If you plan to travel to a distant country where you will not be able to contact your doctor or where
you will temporarily not have the possibility of receiving medical treatment, your doctor may, as a
precaution, prescribe you an antibiotic active against Neisseria meningitidisthat you should carry with
you. If you experience any of the symptoms listed above, you should 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 Epysqli, tell your doctor if you have any ongoing infections.

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

Children and adolescents
Patients under the age of 18 years should be vaccinated against infections caused by Haemophilus

influenzaeand pneumococcus.

Elderly
No special precautions are necessary to treat patients over 65 years of age.

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

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning a pregnancy or are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before taking this medicine.

Women of childbearing potential
The use of effective contraceptive methods during therapy and up to 5 months after the end of therapy
should be considered in women of childbearing potential.

Pregnancy/breastfeeding
If you are pregnant, suspect you are pregnant, are planning a pregnancy or are breastfeeding with breast
milk, ask your doctor or pharmacist for advice before using this medicine.

Driving and using machines
Epysqli does not alter or negligibly alters the ability to drive and use machines.

Epysqlicontains sodium
When diluted with a sodium chloride 9 mg/mL (0.9%) injectable solution, this medicine
contains 0.47 g of sodium (the main component of table salt) per 240 mL at the maximum dose.
This is equivalent to 23.4% of the maximum recommended daily intake with the diet of
an adult. You should take this into account if you are following a low-sodium diet.
When diluted with a sodium chloride 4.5 mg/mL (0.45%) injectable solution, this
medicine contains 0.26 g of sodium (the main component of table salt) per 240 mL at the
maximum dose. This is equivalent to 12.8% of the maximum recommended daily intake with the
diet of an adult. You should take this into account if you are following a low-sodium
diet.

3. How to use Epysqli

At least two weeks before starting treatment with Epysqli, your doctor will administer a
vaccine against meningococcal infection, if the vaccine has not already been administered in
the past or if your vaccination has expired. If your child is not yet of vaccination age or if you
have not been vaccinated at least two weeks before starting treatment with Epysqli, your doctor
will prescribe antibiotics to reduce the risk of infection for up to two weeks after vaccination.
The doctor will administer a vaccine to your child, under the age of 18, against infections from

Haemophilus influenzaeand pneumococcus according to national vaccination recommendations for
each age group.

Instructions for correct use
The therapy will be administered by the doctor or another healthcare professional through the infusion of a
diluted solution of a vial of Epysqli via an intravenous line directly into a vein. It is recommended
that the start of therapy, the so-called "initial phase", continues for 4 weeks and is followed by a
maintenance phase:
If you are using this medicine for the treatment of PNH
For adults:

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

If you are using this medicine for the treatment of SEUa:
For adults:

• Initial phase For the first four weeks, the doctor will administer an intravenous infusion of a diluted solution of Epysqli every week. Each infusion will consist of a dose of 900 mg (3 30 mL vials) and will last 25-45 minutes (35 minutes ± 10 minutes).
• Maintenance phase
• In the fifth week, the doctor will administer an intravenous infusion of a diluted solution of Epysqli with a dose of 1,200 mg (4 30 mL vials) over a period of 25-45 minutes (35 minutes ± 10 minutes).
• After the fifth week, the doctor will administer 1,200 mg of diluted Epysqli solution every two weeks as long-term therapy.

For children and adolescents
Children and adolescents with PNH or SEUa with a body weight equal to or greater than 40 kg
receive the same dosage as adults.
Children and adolescents with PNH or SEUa with a body weight less than 40 kg require a
lower dose based on their weight. Your doctor will calculate it.
For children and adolescents with PNH and SEUa under the age of 18:
After each infusion, you will be observed for about an hour. The doctor's instructions must
be carefully followed.

If you receive more Epysqlithan you should

If you suspect you have received a dose of Epysqli higher than prescribed, ask your
doctor for advice.

If you forget to go to an appointment for Epysqli administration
If you forget an appointment, contact your doctor immediately and refer to
the following paragraph "If you stop treatment with Epysqli".

If you stop treatment with Epysqlifor PNH
Discontinuation or suspension of therapy with Epysqli can cause the symptoms of PNH to return
quickly in a more severe form. The doctor will discuss with you the possible side effects and
explain the risks. The doctor will keep you under close observation for at least 8 weeks.
The risks of stopping Epysqli include increased destruction of red blood cells, which
can cause:

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

If you stop treatment with Epysqli for SEUa
Discontinuation or suspension of therapy with Epysqli can cause the symptoms of
SEUa to return. The doctor will discuss with you the possible side effects and explain the risks. The doctor will keep
you under close observation.
The risks of stopping Epysqli include an increase in platelet inflammation, which
can cause:

• a significant reduction in the number of platelets (thrombocytopenia);
• a significant increase in the destruction of red blood cells;
• decreased urine output (kidney problems);
• increased creatinine levels in the blood (kidney problems);
• symptoms of confusion or alteration of your state 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 everybody gets them.
Before treatment, your doctor will discuss possible side effects with you and explain the risks and benefits of Epysqli.
The most serious side effect was meningococcal sepsis (frequency not known (cannot be estimated based on the available data)).
If you develop symptoms of meningococcal infection (see section 2 “Warning
about meningococcal infection and other infections caused by Neisseria”), you should inform your doctor immediately.
If you are not sure about any of the side effects listed below, 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 (nasopharyngitis), urinary tract infections (urinary tract infection),
• low white blood cell count (leukopenia), reduced red blood cells which can make the skin pale and cause weakness or shortness of breath,
• difficulty sleeping,
• dizziness, high blood pressure,
• upper respiratory tract infections, cough, sore throat (oropharyngeal pain), bronchitis, cold sores (herpes simplex)
• diarrhea, 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, pus collection (abscess), a type of skin infection (cellulitis), influenza, sinusitis, dental infection (abscess), gum infection,
• relatively few platelets in the blood (thrombocytopenia), low level of lymphocytes, a particular type of white blood cells (lymphopenia), awareness of heartbeat,
• severe allergic reaction causing difficulty breathing or dizziness (anaphylactic reaction), hypersensitivity,
• loss of appetite
• depression, anxiety, mood swings, sleep disorder,
• tingling of a part of the body (paresthesia), tremor, altered taste (dysgeusia), fainting,
• blurred vision,
• ringing in the ears, vertigo,
• sudden and rapid onset of extremely high blood pressure, low blood pressure, hot flushes, venous disorder,
• dyspnea (difficulty breathing), nosebleed, nasal congestion, throat irritation, runny nose (rhinorrhea),
• inflammation of the peritoneum (the tissue lining most of the organs in the abdomen), constipation, discomfort in the stomach after meals (dyspepsia), abdominal distension
• urticaria, 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 disease, difficulty or pain when urinating (dysuria), blood in the urine,
• spontaneous erection of the penis,
• swelling (edema), chest discomfort, feeling weak (asthenia), chest pain, pain at the infusion site, chills
• increased liver enzymes, decreased proportion of blood volume occupied by red blood cells, decreased 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), infection by Haemophilus influenzae, impetigo, sexually transmitted bacterial disease (gonorrhea)
• skin tumor (melanoma), bone marrow disease
• destruction of red blood cells (hemolysis), aggregation of cells, abnormal coagulation factor, abnormal blood clotting
• hyperthyroidism (Basedow's disease)
• abnormal dreams
• eye irritation
• bruising
• unusual regurgitation of food from the stomach, gum pain
• yellowing of the skin and/or eyes (jaundice)
• alteration of skin color
• spasm of the muscles of the mouth, swelling of the joints
• menstrual disorders
• abnormal leakage of the infused medicine outside the vein, abnormal sensation at the infusion site, feeling of warmth

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. 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 Epysqli

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the pack 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 Epysqli in the original packaging can be removed from the refrigerator once for a maximum of 2 monthsat room temperature (up to 30 °C), without exceeding the original expiry
date. At the end of this period the product can be returned to the refrigerator.
Store in the original packaging to protect the medicine from light.
After dilution, use the medicine within 24 hours at 2 °C – 8 °C or at room temperature (up to
30 °C). However, if the solution is prepared under aseptic conditions (free from germs), it can be
stored in a refrigerator at 2 ºC – 8 ºC for up to 3 months and for another 72 hours at room temperature (up to
30 ºC) if diluted with an injectable solution of sodium chloride 9 mg/mL (0.9%), an injectable
solution of sodium chloride 4.5 mg/mL (0.45%).
Do not dispose of any medicine in wastewater. Ask your pharmacist how to eliminate medicines that
you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Epysqli Contains

• The active substance is eculizumab (300 mg/30 mL in vial corresponding to 10 mg/mL).
• The other ingredients are:
• monobasic disodium phosphate monohydrate (see section 2 “Epysqli contains sodium”)
• dibasic sodium phosphate heptahydrate (see section 2 “Epysqli contains sodium”)
• trehalose dihydrate
• polysorbate 80 Solvent: water for injections

Description of Epysqli and Package Contents
Epysqli is presented as a concentrate for solution for infusion (30 mL in vial – pack
of 1 vial).
Epysqli is a clear and colorless solution.

Marketing Authorisation Holder and Manufacturer
Samsung Bioepis NL B.V.
Olof Palmestraat 10
2616 LR Delft
The Netherlands

Other Sources of Information
More detailed information on this medicine is available on the European Medicines Agency website, http://www.ema.europa.eu/. In addition, links to other websites on rare diseases and related therapeutic treatments are provided.

Instructions for Use for Healthcare Professionals
Handling of Epysqli
The following information is intended for healthcare professionals only:

• 1- How is Epysqli Supplied?Each vial of Epysqli contains 300 mg of active substance in 30 mL of solution.
• 2- Before AdministrationReconstitution and dilution must be performed in accordance with good preparation practices, in particular with respect to aseptic technique. Epysqli must be prepared for administration by a qualified healthcare professional using aseptic technique.
• Visually inspect the Epysqli solution for the absence of particles or discoloration.
• Withdraw the required amount of Epysqli from the vial(s) using a sterile syringe.
• Transfer the recommended dose into an infusion bag.
• Dilute Epysqli to a final concentration of 5 mg/mL (initial concentration divided by 2) by adding the correct amount of diluent to the infusion bag. For 300 mg doses, use 30 mL of Epysqli (10 mg/mL) and add 30 mL of diluent. For 600 mg doses, use 60 mL of Epysqli and add 60 mL of diluent. For 900 mg doses, use 90 mL of Epysqli and add 90 mL of diluent. For 1200 mg doses, use 120 mL of Epysqli and add 120 mL of diluent. The final volume of the diluted Epysqli 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 1200 mg doses. 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 in water (5%).
• Gently shake the infusion bag containing the diluted Epysqli solution to allow thorough mixing of the medicine and diluent.
• The diluted solution should be allowed to warm to room temperature (up to 30 ºC) before administration by exposing it to ambient air.
• The diluted solution should not be heated in the microwave or by any other heat source other than room temperature.
• Discard any unused portion remaining in the vial.
• Diluted Epysqli solutions can be stored at a temperature of 2° C - 8 °C or at room temperature (up to 30 °C) for 24 hours after removal from the refrigerator. However, if the solution is prepared under aseptic conditions (germ-free), it can be stored in the refrigerator at 2 ºC - 8 ºC for up to 3 months and for another 72 hours at room temperature (up to 30 ºC) if diluted with a sodium chloride 9 mg/mL (0.9%) solution for injection, a sodium chloride 4.5 mg/mL (0.45%) solution for injection.
• 3- Administration
• Do not administer Epysqli with rapid intravenous injections or bolus.
• Epysqli must be administered only by intravenous infusion.
• The diluted Epysqli solution should be administered with an intravenous infusion lasting 25-45 minutes (35 minutes ± 10 minutes) in adult patients and an infusion lasting 1-4 hours in pediatric patients under 18 years of age via a gravity drip, syringe pump, or infusion pump. During administration, the diluted Epysqli solution does not need to be protected from light. The patient should be monitored for one hour after the infusion. If an adverse event occurs during the administration of Epysqli, 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 StorageStore in a refrigerator (2 °C – 8 °C). Do not freeze. Store in the original packaging to protect the medicine from light. Epysqli vials in the original packaging can be removed from the refrigerator once for a maximum of 2 months at room temperature (up to 30 °C), without exceeding the original expiry date. At the end of this period, the product can be returned to the refrigerator. Do not use this medicine beyond the expiry date stated on the packaging and vial label after the words “Expiry”. The expiry date refers to the last day of that month.