XEMBIFY 200 mg /Ml Injectable Solution

Зміст інструкції

1. Xembify 200 mg/mL solution for subcutaneous injection
   1. What is Xembify and what is it used for
   2. What you need to know before using Xembify
   3. How to use Xembify
   4. Possible side effects
   5. How to store Xembify
   6. Contents of the pack and other information

Xembify 200 mg/mL solution for subcutaneous injection

Normal human immunoglobulin (SCIg)

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

1. What is Xembify and what is it used for

What is Xembify
Xembify is a solution of human immunoglobulins (antibodies, mainly immunoglobulin G)
that helps the body fight infections.
Xembify contains immunoglobulins derived from the plasma of healthy people. Immunoglobulins help
fight infections caused by bacteria and viruses. The medicine acts exactly like the
immunoglobulins naturally present in human blood, produced by the immune system.

What is Xembify used for
You are using Xembify because you have excessively low levels of immunoglobulins, due to a
medical condition called immunodeficiency. Xembify infusions increase the levels of
immunoglobulin (antibodies) in the blood, in particular immunoglobulin G (IgG), bringing them back to
normal values.
This medicine is intended for adults, children and adolescents (0-18 years) who do not have
sufficient antibodies (replacement therapy):

• 1. Patients with primary immunodeficiency syndromes (PID), with a congenital deficiency of antibodies.
• 2. Hypogammaglobulinemia (a condition involving low levels of immunoglobulins in the blood) and recurrent bacterial infections in patients with chronic lymphocytic leukemia (a cancer of the blood characterized by the excessive production of white blood cells), in whom antibiotic prophylaxis has not been effective.
• 3. Hypogammaglobulinemia and recurrent bacterial infections in multiple myeloma (a cancer consisting of cells derived from bone marrow).

• 4. Hypogammaglobulinemia in patients after stem cell transplantation (allogeneic hematopoietic stem cell transplantation (HSCT)), when receiving stem cells from another person.

2. What you need to know before using Xembify

Do not use Xembify

• if you are allergic to normal human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6);
• if you have had a severe allergic reaction (e.g. anaphylaxis) to human immunoglobulin in the past;
• if you have antibodies against immunoglobulin A (IgA) in your blood. This can happen if you suffer from IgA deficiency. Since Xembify contains IgA, you may have an allergic reaction;
• by injection into a blood vessel (intravenous route) or into a muscle (intramuscular route).

Inform your doctor, pharmacist or nurse before the infusion of Xembify if you have experienced adverse effects in the past due to an immunoglobulin or one of its components.

Warnings and precautions
Consult your doctor, pharmacist or nurse before using Xembify.

• Inform your doctor if you have had heart disease, blood vessel disease, a blood clot in a blood vessel (e.g. stroke, heart attack or pulmonary embolism), thick blood, diabetes mellitus, high blood pressure, bleeding or coagulation disorder in the past, or if you have been immobile for a certain period. Inform your doctor if you are taking estrogens, usually as contraceptives. You may have an increased risk of developing a blood clot after the infusion of Xembify. Contact your doctor immediately if you experience shortness of breath, chest pain, pain and swelling in an arm or leg, or weakness or numbness on one side of the body. You may have a blood clot in a blood vessel.
• Contact your doctor if you experience severe headache, stiff neck, drowsiness, fever, extreme sensitivity to light, nausea or vomiting. These side effects may occur hours or even a few days after the infusion of Xembify. This could be aseptic meningitis syndrome.
• Xembify can cause kidney problems, including renal failure. Inform your doctor if you have reduced kidney function.
• Xembify may interfere with some blood tests (serological tests). Always inform your doctor about the treatment with Xembify before undergoing blood tests. Allergic reactions

Allergic reactions are rare. However, you may be allergic to immunoglobulins without knowing it. Allergic reactions such as a sudden drop in blood pressure or anaphylactic shock (a sharp decrease in blood pressure with other symptoms, such as swelling of the throat, difficulty breathing and skin rash) are rare, but can occur occasionally even if you have not had adverse effects to immunoglobulins in the past. The risk of allergic reactions is higher if you have IgA deficiency with anti-IgA antibodies. Be sure to inform your doctor if you have IgA deficiency. Xembify contains IgA, which may increase the risk of an allergic reaction.
of an allergic reaction.
Risk of disease transmission
Xembify is purified from human blood obtained from healthy donors. When biological medicines are administered, the possibility of infectious diseases due to the transmission of pathogens cannot be completely excluded. However, in the case of products prepared from human plasma, the risk of pathogen transmission is reduced through: (1) epidemiological controls of the donor population and selection of individual donors through medical interview; (2) screening of individual donations and plasma pools for viral infection markers and (3) processing procedures with demonstrated ability to inactivate/eliminate pathogens.
Despite these measures, when medicines prepared from blood or plasma are administered, the possibility of infection transmission cannot be completely excluded. This also applies to any unknown or emerging viruses or other types of infections.
The measures taken are considered effective for enveloped viruses, such as the human immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A virus. The measures taken may be of limited effectiveness against non-enveloped viruses, such as parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, probably because the antibodies against these infections contained in the product have a protective effect.
It is strongly recommended that you record the name and batch number of the medicine (indicated on the label and packaging after “batch”) each time you receive a dose of this medicine in order to keep a record of the batches used.

Children and adolescents
The warnings and precautions apply to adults, children and adolescents.

Other medicines and Xembify
Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.
Xembify must always be infused alone, without mixing it with other medicines.
If you are to have a vaccination, tell your doctor that you are being treated with Xembify. Xembify may interfere with some vaccines (vaccines containing live viruses), such as measles, mumps, rubella and varicella. You may need to wait up to 3 months after the administration of Xembify before being vaccinated. For the measles vaccine, the waiting time may be up to 1 year.
These interactions apply to children, adults and the elderly.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant or are planning to become pregnant, or if you are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Xembify has not been studied in pregnant women or during breastfeeding, and therefore your doctor or pharmacist will advise you. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the fetus or the child are to be expected. If you are breastfeeding, the immunoglobulins contained in Xembify may also be present in breast milk. These may protect the baby from some infections.
Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

Driving and operating machinery
The ability to drive vehicles and operate machinery may be impaired by some adverse reactions, such as dizziness, associated with Xembify. If you experience adverse reactions during treatment, wait for them to resolve before driving vehicles or operating machinery.

3. How to use Xembify

Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your
doctor.
Xembify must be infused under the skin (subcutaneous administration or s.c.).
Treatment with Xembify will be started by the doctor or nurse. Do not start treatment with
Xembify at home until you have received complete instructions.

Dose
The recommended dose and the administration schedule are established by the doctor. The doctor will calculate
the correct dose for you based on body weight, any previous treatments you have received, and your
response to treatment. Use this medicine following exactly what is stated in this
leaflet or the instructions of the doctor, pharmacist or nurse. If you have any doubts, consult them.
The first dose may be called a “loading dose”, intended to rapidly increase the
levels of immunoglobulins in your blood. The doctor will determine if you need a “loading dose”
(for adults or children) between at least 1 and 2.5 mL/kg of body weight. This loading dose may
be divided over several days.
You will receive Xembify regularly, from once a day to once every 2 weeks; the cumulative dose
per month will be between approximately 1.5 and 5 mL/kg of body weight. The doctor may
adjust the dose depending on the response to treatment.
Do not change this dose or the interval between doses without consulting the doctor first.
If you feel you need a different dose or want to change the administration schedule,
consult the doctor first. Contact your doctor if you miss a dose.
You will need to undergo routine blood tests to measure the level of immunoglobulin in
your blood. Discuss the schedule with your doctor.
There are no differences between the dose for adults, including the elderly (65 years of age and over), and that for
children and infants, as the amount of Xembify infused is based on body weight.

Method of administration
You will receive Xembify by slow infusion under the skin into the fatty tissue (subcutaneous infusion).
Xembify will be administered using a pump or injector. Subcutaneous infusion for
home treatment must be started and monitored by a healthcare professional experienced
in patient guidance for home therapy.
You (or the person caring for you) must receive instructions regarding:

• use of a delivery device, such as a syringe pump, if necessary
• aseptic (germ-free) infusion techniques
• keeping a treatment diary and
• recognizing serious adverse effects and measures to be taken in such cases.

You must carefully follow the doctor's instructions regarding the dose, infusion rate, and schedule for
infusing Xembify, so that the treatment is effective for you.

Infusion sites

Xembify is for subcutaneous infusion only.Xembify must be infused into the subcutaneous tissue, in
sites such as

• abdomen,
• thighs,
• upper arms and
• outer side of the hip. When choosing infusion sites, avoid: areas with bones, visible blood vessels, scars and any areas of inflammation (irritation) or infection. Alternate sites with each administration.

For the first two infusions, the infusion rate will start at 10 mL per hour per infusion site. If
you do not have an adverse effect (see section 4), the rate may be increased every 10 minutes up to
a maximum of 20 mL per hour per infusion site for children and adolescents, and 25 mL/hour
per infusion site for adults. After 2 infusion sessions, the administration rate may be
gradually increased to 35 mL per hour per infusion site. Consult your doctor before
increasing the infusion rate.
It is possible to infuse into more than one site at the same time, provided the sites are at least 5 cm apart. Adults may divide the dose between more sites, especially if the volume is greater
than 30 mL. There is no limit to the number of sites you can use. You can use more than one pump to
do the above.

Instructions for use
Subcutaneous infusion for home treatment must be started and monitored by a
healthcare professional experienced in patient guidance for home therapy. Appropriate infusion pumps may be used for the subcutaneous administration of immunoglobulins. The
patient or the person caring for them must receive instructions regarding the use of the infusion
pump, infusion techniques, keeping a treatment diary, recognizing severe adverse reactions and the measures to be taken if they occur.
Follow the following steps and use aseptic technique to administer Xembify.
Before use, allow the solution to reach room or body temperature (20°C to
37°C). This may take 60 minutes or more.
Do not apply heat or use a microwave oven.

Step 1: Collect the materials
Collect the Xembify vial(s), accessories, sharps container, patient treatment diary/log and infusion pump(s).

Step 2: Clean the surface
Prepare the infusion area on a clean, flat, non-porous surface, such as a kitchen countertop.
Avoid porous surfaces, such as wood. Clean the surface with an alcohol-soaked cotton ball, using
circular motions from the center outwards.

Step 3: Wash your hands
Wash your hands and dry them thoroughly before using Xembify.
The healthcare professional may recommend using antibacterial soap or wearing gloves.

Step 4: Check the vials
The liquid in the vial should be clear to slightly opalescent and colorless or pale yellow or light brown.
Do not use the vial if:

• the solution is cloudy or there are changes in color. The solution should be clear to slightly opalescent and colorless or pale yellow or light brown;
• the tamper-evident cap is missing or there are obvious signs of tampering. Inform the healthcare professional immediately;
• the expiry date has been exceeded.

Step 5: Remove the protective cap
Remove the protective cap from the vial to expose the center of the stopper.
Clean the stopper with alcohol and let it dry.

Step 6: Transfer Xembify from the vial(s) to the syringe
Avoid letting your fingers or other objects touch the internal plunger stem, the tip of the syringe or other
areas that may come into contact with the Xembify solution. Make sure the needles have
caps until the moment of use and that the needles and syringes remain in the clean area
prepared in Step 2. This is called “aseptic technique” and is used to prevent germs from entering
Xembify.
Using aseptic technique, attach each needle to the tip of the syringe.

Step 7: Prepare the syringe and draw the Xembify solution into the syringe
Remove the needle cap.
Pull back the syringe plunger to the level corresponding to the amount of Xembify to
draw from the vial.
Place the Xembify vial on a clean, flat surface and insert the needle into the center of the vial stopper.
Inject air into the vial. The amount of air should correspond to the amount of Xembify to
draw.
Turn the vial upside down and draw the correct amount of Xembify. If more vials are needed
to obtain the correct dose, repeat Steps 4-7.
Administer immediately after transferring Xembify from the vial to the syringe.

Step 8: Prepare the infusion pump
Follow the manufacturer's instructions for preparing the infusion pump, the
infusion set and the Y-connector infusion set, if necessary.
Prime the infusion set with Xembify to remove any air remaining in the infusion set or needle.
To do this, hold the syringe with one hand and the needle covered with the cap of the
infusion set with the other. Gently press the plunger until you see a drop of
Xembify come out of the needle.

Step 9: Choose the number and location of infusion sites
Choose one or more infusion sites according to the instructions of the healthcare professional.
The number and location of the infusion sites depend on the volume of the total dose.
Suitable sites for infusion are: abdomen, thighs, upper arms and outer side of the hip.
Avoid: areas with bones, visible blood vessels, scars and any areas of inflammation
(irritation) or infection.
Alternate sites between future infusions.

Step 10: Prepare the infusion site
Clean the infusion site(s) with a sterile cotton ball soaked in alcohol, starting from the center of each
site and moving outwards in a circular motion. Allow the infusion site(s) to dry (at least 30 seconds).
Before infusion, the sites must be clean, dry and at least 5 cm apart.

Step 11: Insert the needle
Grasp the skin between two fingers (grasp at least 2.5 cm of skin) and insert the needle at a 90-degree angle
into the tissue under the skin (subcutaneous tissue).

Step 12: Make sure the needle is not inserted into a blood vessel
After inserting each needle into the tissue (and before infusion), make sure you have not accidentally penetrated
a blood vessel. To check, connect a sterile syringe to the end of the
infusion set. Pull back the syringe plunger and observe if there is
blood return in the infusion set.
If blood is visible, remove and discard the needle and infusion set.

Repeat priming and steps for inserting the needle using a new needle and infusion set
and choosing another infusion site.
Secure the needle in place by applying a sterile gauze or transparent dressing to the site.

Step 13: Repeat for other sites, if necessary
Step 14: Infuse Xembify
Infuse Xembify as soon as possible after preparation.
Follow the manufacturer's instructions for filling the infusion set and using the infusion pump.

Step 15: After the infusion
Follow the manufacturer's instructions for turning off the pump.
Remove and discard any dressing or tape.
Gently remove the needles or catheters inserted.
Dispose of any unused solution in a suitable waste container, according to instructions.
Dispose of used delivery equipment in a suitable waste container.
Store materials in a safe place.
Follow the manufacturer's instructions for caring for the syringe pump.

Step 16: Record each infusion
Detach the lot number label from the Xembify vial and use it to
complete the patient diary. Include information on each infusion, such as:

• time and date
• dose
• lot number(s)
• infusion sites and
• any reactions.

Remember to bring the diary with you to your doctor's visit. The doctor may ask to
see the diary/treatment log.
Inform your doctor of any problems you encounter during infusions. Contact the healthcare professional
for medical advice regarding adverse effects.

Use in elderly patients
The dose for elderly patients is not considered different from that of patients between 18 and
65 years of age.

Use in children and adolescents
The dose in children and adolescents (0–18 years) is not different from that of adults. In infants and
children, the infusion site may be changed every 5-15 mL.

If you use more Xembify than you should
Contact your doctor for instructions.

If you forget to use Xembify
Do not take a double dose to make up for a missed dose. Contact your doctor for
instructions.
If you have any further questions on the use of this medicine, ask your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Rarely, normal human immunoglobulins can cause a sudden drop in blood
pressure and, in isolated cases, anaphylactic shock, even when the patient has not shown hypersensitivity
to a previous administration.
The signs or symptoms of these rare allergic reactions include:

• feeling of dizziness, lightheadedness or fainting
• skin rash and itching, swelling in the mouth or throat, difficulty breathing, wheezing
• abnormal heart rate, chest pain, bluish discoloration of the lips or fingers of the hands and feet

If you notice signs of an allergic reaction or anaphylactic reaction during the infusion of Xembify,

immediately stop the infusion and contact your doctor or go to the nearest hospital.
these signs during the infusion of Xembify, when administered by a healthcare professional,

immediately inform the doctor or nurse, who will decide whether to slow down the infusion or
stop it completely.
Local reactions may occur at the infusion site, such as swelling, soreness, redness,
hardening (hard nodule), localized heat, itching, bruising and rash.
Xembify can occasionally cause chills, headache, dizziness, fever, vomiting, allergic
reactions, feeling unwell (nausea), joint pain, low blood pressure and
moderate lower back pain.

The following side effect is very common with Xembify (may affect 1 or more people
out of 10):

• Local reaction at the infusion site

The following side effects are common with Xembify (may affect 1 or more people
out of 100):

• Headache
• Arthralgia (joint pain)
• Back pain
• Rhinitis (runny nose, sneezing and nasal congestion)
• Diarrhea
• Nausea
• Pyrexia (fever)
• Decreased blood immunoglobulin G
• Itching
• Papule (small raised area of skin)

Post-marketing adverse effects
The following adverse reactions have been identified and reported during the use of Xembify subsequent
to marketing authorization (all non-serious): dyspnea (shortness of breath), fatigue, pain,
nausea, headache and local reaction at the infusion site, such as erythema (redness) and swelling.
It is not always possible to reliably estimate the frequency of these reactions.

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. You can also report side effects directly
adverse .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Xembify

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

• Store in a refrigerator (2°C - 8°C). Or Xembify can be stored at temperatures not exceeding 25°C for a maximum period of 6 months at any time before the expiry date.

o On the day the product is removed from the refrigerator, write in the appropriate space “Date of
disposal” on the packaging the date corresponding to 6 months from that day or, if earlier,
the expiry date printed on the blister of the packaging.
o If stored at room temperature, do not return the product to the refrigerator.
Use the product within the “Date of disposal” or discard it.

• Do not freeze.
• Keep the vial in the outer packaging to protect the medicine from light.
• Administer as soon as possible after Xembify is transferred from the vial to the syringe.

Do not use this medicine after the expiry date which is stated on the label and the carton.
Do not use this medicine if you notice a change in colour, cloudiness, presence of deposits or if it has
been frozen.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Xembify contains

• The active substance is normal human immunoglobulin (SCIg), 1 mL contains 200 mg of normal human immunoglobulin, of which at least 98% is IgG. The percentage of IgG subclasses is approximately 62% IgG, 30% IgG, 4.3% IgG and 3.2% IgG. It contains IgA (no more than 160 micrograms/mL).
• The other ingredients are glycine (E 640), polysorbate 80 (E 433) and water for injections.

Description of the appearance of Xembify and contents of the pack
Xembify is a solution for subcutaneous injection. The solution is from clear to slightly
opalescent and colourless or pale yellow or light brown.
Xembify is packaged in a carton and is contained in a transparent glass vial with a stopper,
aluminium crimp seal, plastic cap and tamper-evident band guaranteeing the integrity
of the packaging.
Xembify is supplied in packs of
1 or 10 vials containing 1 g of normal human immunoglobulin in 5 mL solution for subcutaneous
injection
1, 10 or 20 vials containing 2 g of normal human immunoglobulin in 10 mL solution for
subcutaneous injection
1 or 20 vials containing 4 g of normal human immunoglobulin in 20 mL solution for
subcutaneous injection
1 or 10 vials containing 10 g of normal human immunoglobulin in 50 mL solution for subcutaneous
injection
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - Spain

Other sources of information
More detailed information on this medicine is available on the website of the Italian Medicines
Agency, Website: https://www.aifa.gov.it .