Xembify

Patient Information Leaflet

Xembify 200 mg/ml solution for subcutaneous injection
Human normal immunoglobulin (SCIg)
This medicinal product will be subject to additional monitoring. This will allow for rapid
identification of new safety information. Patients can also help by reporting any suspected
adverse reactions that occur after using the medicine. For information on how to report
adverse reactions, see section 4.
Please read all of this leaflet carefully before using this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm someone else, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents

1. What Xembify is and what it is used for
2. Important information before using Xembify
3. How to use Xembify
4. Possible adverse reactions
5. How to store Xembify
6. Contents of the pack and other information

1. What Xembify is and what it is used for

What Xembify is
Xembify is a solution of human immunoglobulins (antibodies, mainly immunoglobulin G) that help the body fight infections.
Xembify contains immunoglobulins derived from plasma of healthy individuals. Immunoglobulins help the body fight infections caused by bacteria and viruses. This medicine works in the same way as naturally occurring immunoglobulins produced by the immune system and present in human blood.

What Xembify is used for
Patients receiving Xembify have abnormally low levels of immunoglobulins due to a condition called immunodeficiency. Xembify infusions increase the level of immunoglobulins (antibodies), particularly immunoglobulin G (IgG), in the patient's blood to normal levels.

This medicine is intended for adults, children, and adolescents (0–18 years) who do not produce sufficient antibodies (replacement therapy):

1. Patients with primary immunodeficiency (PID) syndromes involving congenital antibody deficiency.
2. Hypogammaglobulinaemia (a condition characterised by low levels of immunoglobulins in the blood) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a blood cancer involving excessive production of white blood cells), in whom prophylactic antibiotic treatment has proven ineffective.
3. Hypogammaglobulinaemia and recurrent bacterial infections in patients with multiple myeloma (a cancer of bone marrow cells).
4. Hypogammaglobulinaemia in patients after allogeneic haematopoietic stem cell transplantation (HSCT) from another person.

2. Important information before using Xembify

When not to use Xembify

• if the patient is allergic to normal human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6);
• if the patient has previously experienced a severe allergic reaction (such as anaphylaxis) to human immunoglobulin;
• if the patient has antibodies against immunoglobulin A (IgA) in their blood. This may occur in cases of IgA deficiency. Since Xembify contains IgA, an allergic reaction may occur;
• this medicine must not be administered by intravenous (into a blood vessel) or intramuscular (into a muscle) infusion.

Before administering Xembify, tell the doctor, pharmacist, or nurse if the patient has ever experienced adverse reactions after receiving immunoglobulin or any of the ingredients of this medicine.
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before starting treatment with Xembify.

• Inform your doctor if the patient has previously had heart disease, blood vessel disorders, blood clots in blood vessels (such as stroke, heart attack, or pulmonary embolism), thick blood, diabetes, high blood pressure, bleeding disorders, or clotting disorders, or if the patient has been immobile for a period of time. Inform your doctor if the patient is taking estrogens, usually as a contraceptive. There may be an increased risk of blood clots after infusion of Xembify. If shortness of breath, chest pain, pain and swelling in the arm or leg, or weakness or numbness on one side of the body occurs, contact the doctor immediately. These may be signs of a blood clot in a blood vessel.
• Contact the doctor if the patient experiences a severe headache, neck stiffness, drowsiness, fever, light sensitivity, nausea, or vomiting. These adverse reactions may occur within hours or even days after administration of Xembify. They may indicate the occurrence of aseptic meningitis.
• Xembify may cause kidney problems, including kidney failure. Inform the doctor if the patient has reduced kidney function.
• Xembify may affect the results of certain blood tests (serological tests). Always inform the doctor about taking Xembify before any blood test.

Allergic reactions
Allergic reactions are rare. However, it is possible to be allergic to immunoglobulins without knowing it. Allergic reactions, such as sudden drop in blood pressure or anaphylactic shock (rapid drop in blood pressure with other symptoms such as throat swelling, difficulty breathing, and skin rash), are rare but may occur, even if no adverse reactions occurred previously with immunoglobulin administration. The risk of allergic reactions is increased if the patient has IgA deficiency with anti-IgA antibodies. Remember to inform the doctor if the patient has IgA deficiency. Xembify contains some IgA, which may increase the risk of an allergic reaction. Section 4 of the leaflet ("Possible side effects") lists the objective and subjective symptoms of allergic reactions.
Risk of disease transmission
Xembify is a purified product derived from human plasma obtained from healthy donors. When administering biological medicinal products, it is not possible to completely exclude the risk of infectious diseases caused by transmission of infectious agents. However, for products prepared from human plasma, the risk of transmission of infectious agents is reduced due to: (1) epidemiological monitoring of donor populations and selection of individual donors based on medical interviews; (2) screening tests of individual donations and plasma pools for markers of viral infection; and (3) manufacturing procedures proven to inactivate/remove infectious agents.
Despite these measures, when administering medicines prepared from human blood or plasma, it is not possible to completely exclude the risk of transmitting infections, including unknown or newly emerging viruses or other types of infections.
The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus, as well as non-enveloped hepatitis A virus.
The measures may have limited effectiveness against non-enveloped viruses such as parvovirus B19.
Administration of immunoglobulins has not been associated with transmission of hepatitis A virus or parvovirus B19, likely because the antibodies against these infections present in the product have a protective effect.
It is strongly recommended that each time the patient receives a dose of this medicine, the name and batch number of the medicine (shown on the label and carton after "Batch No.") should be recorded to maintain a record of the batches used.
Children and adolescents
Warnings and precautions apply to adults, children, and adolescents.
Xembify with other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking, has recently taken, or plans to take.
Xembify must always be administered separately and must not be mixed with other medicines.
If the patient plans to receive a vaccine, they should inform the doctor that they are being treated with Xembify. Xembify may affect the effectiveness of certain vaccines (vaccines containing live viruses), such as vaccines against measles, mumps, rubella, and varicella. It may be necessary to wait up to 3 months after receiving Xembify before vaccination can be given. For the measles vaccine, it may be necessary to wait up to 1 year.
These interactions apply to children, adults, and elderly patients.
Pregnancy, breastfeeding, and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a baby, she should consult her doctor or pharmacist before using this medicine.
Studies on the use of Xembify in pregnant or breastfeeding women have not been conducted; therefore, the doctor or pharmacist will provide guidance. Clinical experience with the use of immunoglobulins suggests that harmful effects on pregnancy or the unborn child and infant are unlikely. In breastfeeding women, the immunoglobulins contained in Xembify may pass into breast milk and may protect the infant against certain infections. Clinical experience with the use of immunoglobulins suggests that harmful effects on fertility are unlikely.
Driving and operating machinery
Some adverse reactions associated with the use of Xembify, such as dizziness, may negatively affect the ability to drive or operate machinery. If adverse reactions occur during treatment, the patient should wait until symptoms resolve before driving or operating machinery.

3. How to use Xembify

This medicine should always be used as directed by a physician. If in doubt, consult
your doctor.
Xembify must be administered by subcutaneous infusion (subcutaneous administration, s.c.).
Treatment with Xembify will be initiated by a physician or nurse. Do not begin treatment with
Xembify at home until you have received detailed instructions.
Dosage
The recommended dose and dosing schedule will be determined by your physician. The physician will calculate the appropriate dose for you based on body weight, previous treatment received, and response to therapy. This medicine should always be used as described in this leaflet or as directed by your physician, pharmacist, or nurse. If in doubt, consult your physician, pharmacist, or nurse.
The first dose may be a so-called "loading dose," intended to rapidly increase immunoglobulin levels in the blood. Your physician will determine whether a loading dose (in adults or children) of at least 1 to 2.5 ml/kg body weight is required. Administration of the loading dose may be spread over several days.
You will receive Xembify regularly, with a frequency ranging from once daily to once every two weeks; the cumulative monthly dose will be approximately 1.5 to 5 ml/kg body weight. Your physician may adjust the dose depending on your response to treatment.
Do not change this dose or the interval between doses without first consulting your physician.
If you believe you should receive a different dose or wish to modify the dosing schedule, you must first discuss this with your physician. If a dose is missed, contact your physician.
Routine blood tests will be necessary to monitor immunoglobulin levels in the blood. Discuss the testing schedule with your physician.
There is no difference in dosing between adults, including elderly individuals (65 years and older), and children or infants, because the amount of Xembify administered via infusion is based on body weight.
Method of administration
Xembify will be administered by slow subcutaneous infusion into fatty tissue. Xembify will be administered using an infusion pump or syringe driver. Subcutaneous infusions for home treatment must be initiated and monitored by a healthcare professional experienced in managing patients receiving home therapy.
The patient (or caregiver) must be trained in:

• use of the drug delivery device, e.g., syringe pump, if required;
• aseptic techniques for administering infusions;
• maintaining a treatment diary;
• recognizing serious adverse reactions and actions to take if they occur.

To ensure effective treatment, strictly follow your physician's instructions regarding dose, infusion rate, and administration schedule for Xembify.
Infusion sites
Xembify is intended exclusively for subcutaneous infusion. Xembify is injected into subcutaneous tissue at the following sites:

• abdomen;
• thigh;
• upper arm;
• lateral hip.

When selecting an infusion site, avoid areas with bones, visible blood vessels, scars, or areas with inflammation (irritation) or infection. The infusion site must be changed with each administration.
During the first two infusions, the initial infusion rate is 10 ml per hour per site. If no adverse reactions occur (see section 4), the infusion rate may be increased every 10 minutes up to a maximum of 20 ml per hour per site in children and adolescents, and 25 ml per hour per site in adults. After two infusions, the infusion rate may be gradually increased up to 35 ml per hour per site. Discuss any increase in infusion rate with your physician beforehand.
Infusions may be administered simultaneously at multiple sites, provided the sites are at least 5 cm apart. In adults, the dose may be divided across multiple infusion sites, especially if the volume exceeds 30 ml. There is no limit to the number of infusion sites. More than one pump may be used simultaneously.
Instructions for use
Subcutaneous infusions for home treatment must be initiated and monitored by a qualified healthcare professional experienced in managing patients receiving home therapy. Infusion pumps suitable for subcutaneous administration of immunoglobulins may be used. The patient or caregiver must be trained in the use of the infusion pump, infusion administration techniques, maintaining a treatment diary, and recognizing serious adverse reactions and actions to take if they occur.
Follow the steps below and use aseptic technique when administering Xembify.
Allow the solution to reach room temperature or body temperature (20°C to 37°C) before use. This may take 60 minutes or longer.
Do not heat or place in a microwave.
Step 1: Gather materials
Prepare the vial(s) of Xembify, supplies, sharps container, patient treatment diary/infusion log, and infusion pump(s).
Step 2: Prepare a clean work area
Prepare a clean, flat, non-porous surface, such as a kitchen countertop.
Avoid using porous surfaces such as wood. Clean the surface with an alcohol wipe, using circular motions from the center outward.
Step 3: Wash hands
Wash and dry hands thoroughly before using Xembify.
The healthcare professional may recommend using antibacterial soap or wearing gloves.

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

• the solution is cloudy or discolored. The solution should be clear to slightly opalescent, colorless, pale yellow, or light brown;
• the protective cap is missing or there are visible signs of tampering. Immediately inform the healthcare professional;
• the expiration date has passed.

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

Step 6: Transfer Xembify from vial(s) to syringe
Do not touch the inner plunger rod, syringe tip, or any other parts that may come into contact with Xembify solution with fingers or other objects. Ensure that needles remain capped until use and that needles and syringes are placed on the clean area prepared in Step 2. This procedure is known as "aseptic technique," intended to prevent microbial contamination of Xembify.
Following aseptic technique, attach each needle to the syringe tip.

Step 7: Prepare syringe and draw up Xembify solution
Remove the needle cap.
Pull back the syringe plunger to the level corresponding to the amount of Xembify to be drawn 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 volume of air should equal the volume of Xembify to be drawn.
Invert the vial and draw the appropriate volume of Xembify. If multiple vials are required to administer the correct dose, repeat steps 4–7.
Administer immediately after transferring Xembify from the vial to the syringe.

Step 8: Prepare infusion pump
Follow the manufacturer's instructions for preparing the infusion pump, administration set, and Y-connector if used.
Completely fill the administration set with Xembify to remove any air remaining in the tubing or needle. To do this, hold the syringe in one hand and the needle of the administration set (with protective cap) in the other. Gently press the plunger until a drop of Xembify appears at the needle tip.
Step 9: Select number and location of infusion sites
Select one or more infusion sites as directed by the healthcare professional.
The number and location of infusion sites depend on the total dose volume.
Suitable infusion sites include the abdomen, thighs, upper arms, and lateral hips.
Avoid areas with bones, visible blood vessels, scars, or areas with inflammation (irritation) or infection.
Change infusion sites with each administration.

Step 10: Prepare infusion site(s)
Clean the infusion site(s) with an antiseptic wipe, using circular motions from the center outward. Allow the site(s) to dry (at least 30 seconds).
Infusion sites should be clean, dry, and at least 5 cm apart before administration.

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

Step 12: Check that the needle has not entered a blood vessel
After inserting each needle into subcutaneous tissue (and before starting the infusion), check for accidental puncture of a blood vessel. Attach a sterile syringe to the end of the filled administration set. Pull back the syringe plunger and observe whether blood enters the tubing.
If blood is visible, remove and discard the needle and administration set.

Repeat the filling and needle insertion steps using a new needle, new administration set, and a new infusion site.
Secure the needle in place by applying sterile gauze or a transparent dressing over the infusion site.

Step 13: Repeat procedure at other infusion sites if needed
Step 14: Administer Xembify infusion
Administer Xembify as soon as possible after preparation.
Follow the manufacturer's instructions for filling the administration set and using the infusion pump.
Step 15: Post-infusion procedures
Follow the manufacturer's instructions to turn off the pump.
Remove and discard the dressing or tape.
Carefully remove the inserted needle(s) or catheter(s).
Dispose of unused solution into an appropriate waste container as directed.
Dispose of used administration equipment into an appropriate waste container.
Store supplies in a safe place.
Follow the manufacturer's instructions for syringe pump maintenance.
Step 16: Record each infusion
Peel off the batch number label from the Xembify vial and attach it to the patient's records. Include information about each infusion, such as:

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

Remember to bring your treatment diary to physician visits. Your physician may request to review your treatment diary/infusion log.
Inform your physician of any problems that occurred during the infusion. Contact your healthcare professional for medical advice regarding adverse reactions.
Use in elderly patients
Dosing in elderly patients does not differ from dosing in patients aged 18–65 years.
Use in children and adolescents
Dosing in children and adolescents (0–18 years) does not differ from dosing in adults.
In infants and children, the infusion site may be changed every 5 to 15 ml.
Administration of a higher than recommended dose of Xembify
Seek instructions from your physician.
Missed dose of Xembify
Do not administer a double dose to make up for a missed dose. Seek instructions from your physician.
If you have any further questions about the use of this medicine, consult your physician.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
In rare cases, human normal immunoglobulins may cause a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even if the patient has not previously shown signs of hypersensitivity after prior administration.
Objective or subjective symptoms of these rare allergic reactions include:

• dizziness, lightheadedness, or feeling weak (as before fainting);
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing;
• irregular heart rate, chest pain, bluish discoloration of lips or fingers.

If any symptoms of an allergic or anaphylactic-type reaction occur during infusion of Xembify, the infusion must be stopped immediately and a doctor should be contacted or the nearest hospital visited. See section 2 of this leaflet ("Warnings and precautions"). If any of these symptoms occur during Xembify infusion administered by a healthcare professional, the doctor or nurse must be informed immediately. They will decide whether to slow down or completely stop the infusion.
Local reactions at the infusion site may occur, such as swelling, pain, redness, induration (hard lump), local increase in skin temperature, itching, bruising, and rash.
Xembify may sometimes cause chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain.
The following adverse reaction is very common with Xembify (may occur in 1 or more out of 10 people):

• reaction at the infusion site.

The following adverse reactions are common with Xembify (may occur in 1 or more out of 100 people):

• headache;
• joint pain;
• back pain;
• nasal catarrh (runny nose, sneezing, and nasal congestion);
• diarrhoea;
• nausea;
• fever;
• pruritus (itching);
• papular rash (small raised bumps on the skin surface).

Adverse reactions reported after product introduction to the market
After Xembify was introduced to the market, the following adverse reactions have been identified and reported (none of which were severe): dyspnoea, fatigue, pain, nausea, headache, and reactions at the infusion site such as erythema (skin redness) and swelling.
Reliable estimation of the frequency of these reactions is not always possible.
Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, PL-02 222 Warsaw, Tel.: + 48 22 49 21 301, Fax: + 48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl.
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to provide more information on the safety of the 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).
  Xembify may be stored at temperatures not exceeding 25°C for up to 6 months before the expiry date.
  On the day the product is removed from the refrigerator, enter the date 6 months from removal or the expiry date printed on the carton flap, whichever comes first, in the designated space on the carton („removal date”).
  If stored at room temperature, do not return the medicine to the refrigerator. The medicine must be used before the „removal date” or discarded.
• Do not freeze.
• Keep the vial in the outer packaging to protect from light.
• Administer as soon as possible after transferring Xembify from the vial to the syringe.

Do not use this medicine after the expiry date stated on the label and carton.
Do not use this medicine if you notice that it is discoloured, cloudy, contains particles, or has been frozen.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Xembify contains

• The active substance is human normal immunoglobulin (SCIg); one ml contains 200 mg of human normal immunoglobulin, of which at least 98% is IgG. The percentage content of IgG subclasses is approximately 62% IgG_, 30% IgG_, 4.3% IgG_, and 3.2% IgG_. The medicine contains a small amount of IgA (not more than 160 micrograms/ml).
• Other ingredients: glycine (E 640), polysorbate 80 (E 433), and water for injections.

What Xembify looks like and contents of the pack
Xembify is a solution for subcutaneous injection. The solution is clear to slightly opalescent and colourless, pale yellow or light brown.
Xembify is packed in a cardboard box containing a transparent glass vial with a stopper, an aluminium seal, a plastic cap, and a tamper-evident shrink band, ensuring the integrity of the packaging.
Xembify is supplied in the following pack sizes:
1 or 10 vials containing 1 g of human normal immunoglobulin in 5 ml of solution for subcutaneous injection
1, 10 or 20 vials containing 2 g of human normal immunoglobulin in 10 ml of solution for subcutaneous injection
1 or 20 vials containing 4 g of human normal immunoglobulin in 20 ml of solution for subcutaneous injection
1 or 10 vials containing 10 g of human normal immunoglobulin in 50 ml of solution for subcutaneous injection
Each cardboard box contains 1, 10 or 20 vials of Xembify and 1 patient information leaflet.
Not all pack sizes may be marketed.
Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
c/Can Guasch, 2
08150 Parets del Valles
Barcelona, Spain
Other sources of information
Detailed information on this medicine is available on the website of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, www.urpl.gov.pl.