Xembifi

Leaflet accompanying the packaging: patient information

Xembify 200 mg/ml solution for subcutaneous injection

Human normal immunoglobulin (SCIg)
This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. You can help by reporting any side effects you may get. To learn how to report side effects, see section 4.

You should carefully read the contents of this leaflet before using the medicine, as it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• If you have any doubts, you should consult a doctor, pharmacist, or nurse.
• This medicine has been prescribed specifically for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If the patient experiences any side effects, including any not listed in this leaflet, they should tell their doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet

• 1. What is Xembify and what is it used for
• 2. Important information before using Xembify
• 3. How to use Xembify
• 4. Possible side effects
• 5. How to store Xembify
• 6. Contents of the packaging 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), which help the body fight infections.
Xembify contains immunoglobulins derived from the plasma of healthy individuals. Immunoglobulins help fight infections caused by bacteria and viruses. The drug works exactly like naturally occurring immunoglobulins, produced by the immune system and present in human blood.

What is Xembify used for

In patients using Xembify, there is an abnormally low concentration of immunoglobulins due to a disease called immunodeficiency. Xembify infusions increase the concentration of immunoglobulins (antibodies), particularly immunoglobulin G (IgG), in the patient's blood to a normal level.
This drug is intended for adults, children, and adolescents (0-18 years) who do not have enough antibodies (replacement therapy):

• 1. Patients with primary immunodeficiency syndromes (PID) with a congenital lack of antibodies.
• 2. Hypogammaglobulinemia (a condition characterized by low immunoglobulin levels in the blood) and recurrent bacterial infections in patients with chronic lymphocytic leukemia (a blood cancer in which too many white blood cells are produced), in whom prophylactic antibiotic treatment has been ineffective.

• 3. Hypogammaglobulinemia and recurrent bacterial infections in patients with multiple myeloma (a bone marrow cancer).
• 4. Hypogammaglobulinemia in patients after hematopoietic stem cell transplantation (allogeneic hematopoietic stem cell transplantation, HSCT) from another person.

2. Important information before using Xembify

When not to use Xembify

• if the patient is allergic to human normal immunoglobulin or any of the other ingredients of this medicine (listed in section 6);
• if the patient has had a severe allergic reaction (such as anaphylaxis) to human immunoglobulin;
• if the patient has antibodies against immunoglobulin A (IgA). This may occur in IgA deficiency. Since Xembify contains IgA, an allergic reaction may occur;
• the drug is not administered by intravenous infusion or intramuscularly.

Before administering Xembify, you should tell your doctor, pharmacist, or nurse if you have ever experienced side effects after receiving immunoglobulin or any of the ingredients of the drug.

Warnings and precautions

Before starting treatment with Xembify, you should discuss it with your doctor, pharmacist, or nurse.

• You should tell your doctor if you have a history of heart disease, vascular disease, blood clots in a blood vessel (such as stroke, heart attack, or pulmonary embolism), thick blood, diabetes, high blood pressure, bleeding, or coagulation disorders, or if you have been immobilized for a period. You should tell your doctor if you are taking estrogens, usually as a contraceptive. After Xembify infusion, there may be a higher risk of blood clots. If you experience shortness of breath, chest pain, pain and swelling of the arm or leg, or weakness or numbness on one side of the body, you should contact your doctor immediately. This may indicate a blood clot in a blood vessel.
• You should consult your doctor if you experience severe headache, neck stiffness, drowsiness, fever, hypersensitivity to light, nausea, or vomiting. These side effects may occur within a few hours or even a few days after Xembify administration. This may indicate the development of aseptic meningitis.
• Xembify may cause kidney problems, including kidney failure. You should tell your doctor if you have reduced kidney function.
• Xembify may affect the results of some blood tests (serological tests). Before each blood test, you should always tell your doctor that you are taking Xembify.

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 sudden drop in blood pressure with other symptoms, such as throat swelling, difficulty breathing, and skin rash), are rare but can occur, even if you have not experienced any side effects in the past related to immunoglobulin administration. There is an increased risk of allergic reactions if you have IgA deficiency with anti-IgA antibodies. You should remind your doctor if you have IgA deficiency. Xembify contains some IgA, which may increase the risk of an allergic reaction. In section 4 of the leaflet ("Possible side effects"), the objective and subjective symptoms of an allergic reaction are listed.
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 rule out the possibility of transmitting infectious diseases caused by the transmission of pathogens. However, for products prepared from human plasma, the risk of transmitting pathogens is reduced due to: (1) epidemiological control of the donor population and selection of individual donors based on medical history; (2) screening of individual donations and plasma pools for viral infection markers; and (3) procedures in the manufacturing process with proven ability to inactivate/remove pathogens.
Despite these measures, when administering drugs prepared from human blood or plasma, it is not possible to completely rule out the possibility of transmitting an infection. This also applies to all unknown or newly emerging viruses or other types of infections.
The measures taken are considered effective for 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 taken may have limited value for non-enveloped viruses, such as parvovirus B19.
Immunoglobulin administration has 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 each time the patient receives a dose of this medicine, the name and batch number of the medicine (indicated on the label and packaging) be recorded to keep a record of the batches used.

Children and adolescents

Warnings and precautions apply to adults, children, and adolescents.

Xembify and other medicines

You should tell your doctor or pharmacist about all medicines you are currently taking or have recently taken, as well as any medicines you plan to take.
Xembify should always be administered separately, without mixing with other medicines.
If you plan to receive a vaccine, you should tell your doctor that you are being treated with Xembify. Xembify may affect the efficacy of some vaccines (live virus vaccines), such as measles, mumps, rubella, and chickenpox vaccines.
It may be necessary to wait up to 3 months after receiving Xembify before receiving a vaccine. For measles vaccine, it may be necessary to wait up to 1 year.
These interactions apply to children, adults, and the elderly.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a child, you should consult your doctor or pharmacist before using this medicine.
No studies have been conducted on the use of Xembify in pregnant or breastfeeding women, so your doctor or pharmacist will provide guidance. Clinical experience with immunoglobulins suggests that no harmful effects on pregnancy or the fetus and child are expected. In breastfeeding women, the immunoglobulins in Xembify may pass into breast milk and may protect the child from some infections. Clinical experience with immunoglobulins suggests that no harmful effects on fertility are expected.

Driving and using machines

Some side effects associated with Xembify, such as dizziness, may adversely affect your ability to drive or use machines. If you experience side effects during treatment, you should wait until the symptoms have resolved before driving or using machines.

3. How to use Xembify

This medicine should always be used as directed by your doctor. If you are unsure, you should consult your doctor.
Xembify should be administered by subcutaneous infusion (subcutaneous administration, s.c.).
Xembify treatment will be initiated by your doctor or nurse. You should not start Xembify treatment at home until you have received detailed instructions.

Dose

The recommended dose and dosing schedule will be determined by your doctor. Your doctor will calculate the appropriate dose for you based on your body weight, previous treatment you have received, and your response to treatment. This medicine should always be used as described in this leaflet or as directed by your doctor, pharmacist, or nurse. If you are unsure, you should consult your doctor, pharmacist, or nurse.
The first dose may be a so-called "loading dose," which aims to rapidly increase the concentration of immunoglobulins in the blood. Your doctor will determine if a loading dose (for adults or children) of at least 1 to 2.5 ml/kg body weight is needed. Administration of the loading dose can be divided over several days.
You will receive Xembify regularly, with a frequency of once a day to once every 2 weeks; the cumulative monthly dose will be approximately 1.5 to 5 ml/kg body weight. Your doctor may adjust the dose based on your response to treatment.
You should not change this dose or the time to the next dose without consulting your doctor first.
If you think you should receive a different dose or want to modify the dosing schedule, you must first talk to your doctor. If you miss a dose, you should contact your doctor.
Regular blood tests will be necessary to determine the concentration of immunoglobulin in your blood. The schedule for these tests should be discussed with your doctor.
There is no difference in dosing for adults, including the elderly (65 years and older), and children and infants, as the amount of Xembify administered by infusion is determined based on body weight.

Method of administration

Xembify will be administered by slow subcutaneous infusion into the fatty tissue. Xembify will be administered using a pump or syringe. Subcutaneous infusion at home must be initiated and monitored by a healthcare professional with experience in managing patients at home.
The patient (or their caregiver) should be instructed on:

• using the device to administer the medicine, such as a syringe pump if necessary;
• aseptic (germ-free) methods of infusion;
• keeping a treatment diary;
• recognizing severe side effects and the measures to be taken in case they occur.

For treatment to be effective, you should strictly follow your doctor's instructions regarding the dose, infusion rate, and administration schedule of Xembify.

Infusion sites

Xembify is intended for subcutaneous infusion only. Xembify is injected into the subcutaneous tissue in areas such as:

• abdomen;
• thigh;
• arm;
• hip side.

When choosing an infusion site, you should avoid areas where bones, visible blood vessels, scars, or inflamed (irritated) or infected areas are located. The infusion site should be changed each time.
For the first two infusions, the initial infusion rate is 10 ml per hour per infusion site. If you do not experience side effects (see section 4), the infusion rate can be increased every 10 minutes to a maximum of 20 ml per hour per infusion site in children and adolescents and 25 ml per hour per infusion site in adults. After two infusions, the infusion rate can be gradually increased to 35 ml per hour per infusion site. Before increasing the infusion rate, you should discuss it with your doctor.
Infusion can be administered simultaneously at multiple sites, provided they are at least 5 cm apart. In adults, the dose can be divided into multiple infusion sites, especially if the dose volume is greater than 30 ml. There is no limit to the number of infusion sites. More than one pump can be used at the same time.

Instructions for use

Subcutaneous infusion at home must be initiated and monitored by a qualified healthcare professional with experience in managing patients at home. Suitable infusion pumps for subcutaneous administration of immunoglobulins can be used. The patient or their caregiver should be instructed on the use of the infusion pump, methods of infusion, keeping a treatment diary, and recognizing severe side effects and the measures to be taken in case they occur.
You should follow the steps below and use aseptic technique when administering Xembify.
Before use, you should wait until the solution has reached room temperature or body temperature (between 20°C and 37°C). This may take 60 minutes or longer.
Do not heat or microwave.

Step 1: gathering materials

Prepare the Xembify vial(s), ancillary materials, sharps container, patient treatment diary/infusion log, and infusion pump (pumps).

Step 2: preparing a clean work surface

Prepare a work surface on a clean, flat, non-porous surface, such as a kitchen counter.
Avoid using porous surfaces, such as wood. Clean the surface with an alcohol swab, moving in a circular motion from the center outwards.

Step 3: washing hands

Before using Xembify, you should wash and dry your hands thoroughly.
A healthcare professional may recommend using antibacterial soap or wearing gloves.

Step 4: checking the 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 signs of tampering. You should immediately inform a healthcare professional;
• the expiration date has passed.

Step 5: removing the protective cap

Remove the protective cap from the vial to expose the central part of the stopper.
Wipe the stopper with alcohol and let it dry.

Step 6: transferring Xembify from the vial to the syringe

Do not touch the inside of the plunger, the tip of the syringe, or other areas that may come into contact with the Xembify solution with your fingers or other objects. Ensure that the needles and syringes are covered with their protective caps until use and lie on a clean area prepared in step 2. This is called "aseptic technique," which is designed to prevent contamination of Xembify with microorganisms.
Following aseptic technique, attach each needle to the tip of the syringe.

Step 7: preparing the syringe and drawing up the Xembify solution

Remove the needle cover.
Pull the syringe plunger back 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 correspond to the volume of Xembify to be drawn.
Invert the vial and draw up the required volume of Xembify. If multiple vials are needed to administer the correct dose, repeat steps 4-7.
Administer immediately after transferring Xembify from the vial to the syringe.

Step 8: preparing the infusion pump

Follow the manufacturer's instructions for preparing the infusion pump, infusion set, and Y-connector, if used.
Completely fill the infusion set with Xembify to remove any air remaining in the set or needle. To do this, hold the syringe in one hand and the protected needle of the infusion set in the other.
Gently press the plunger until a drop of Xembify appears at the tip of the needle.

Step 9: selecting the number and location of infusion sites

Choose one or more infusion sites as recommended by your healthcare professional.
The number and location of infusion sites depend on the total dose volume.
Appropriate infusion sites include the abdomen, thighs, arms, and hips.
Avoid areas where bones, visible blood vessels, scars, or inflamed (irritated) or infected areas are located.
Change the infusion site for each subsequent infusion.

Step 10: preparing the infusion site

Clean the infusion site(s) with an antiseptic swab, moving in a circular motion from the center outwards. Allow the site(s) to dry (for at least 30 seconds).
Before infusion, the site(s) should be clean, dry, and at least 5 cm apart.

Step 11: inserting the 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 the subcutaneous tissue).

Step 12: checking if the needle has not been inserted into a blood vessel

After inserting each needle into the subcutaneous tissue (and before administering the infusion), you should check if the needle has accidentally entered a blood vessel. To do this, attach a sterile syringe to the end of the filled infusion set. Pull the syringe plunger back and observe if blood enters the infusion set.
If you see blood, remove and discard the needle and infusion set.

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

Step 13: repeating the steps at other infusion sites if necessary

Step 14: administering the Xembify infusion

Administer Xembify as soon as possible after preparation.
Follow the manufacturer's instructions for filling the infusion 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).
Discard any unused solution in an appropriate waste container, as instructed.
Discard the used administration equipment in an appropriate waste container.
Store materials in a safe place.
Follow the manufacturer's instructions for maintaining the syringe pump.

Step 16: recording each infusion

Remove the label with the batch number 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 site(s');
• any reactions.

You should keep the treatment diary with you when you visit your doctor. Your doctor may ask to see the treatment diary/infusion log.
You should tell your doctor about any problems that occurred during the infusion. You should contact a healthcare professional for medical advice on side effects.

Use in elderly patients

Dosing in elderly patients is not different from that in patients aged 18-65 years.

Use in children and adolescents

Dosing in children and adolescents (0-18 years) is not different from that in adults.
In infants and children, the infusion site can be changed every 5 to 15 ml.

Overdose of Xembify

To obtain instructions, you should consult your doctor.

Missed dose of Xembify

You should not take a double dose to make up for a missed dose. To obtain instructions, you should consult your doctor.
If you have any further doubts about using this medicine, you should consult your doctor.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Human normal immunoglobulins may rarely cause a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even if the patient has not shown hypersensitivity to previous immunoglobulin administration.
The objective and subjective symptoms of these rare allergic reactions include:

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

Local reactions may occur at the infusion site, such as swelling, pain, redness, induration (hard lump), local increase in skin temperature, itching, bluish discoloration, and rash.
Xembify may occasionally cause chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain.

The following side effect occurs very frequently when using Xembify (may affect 1 or more in 10 people):

• infusion site reaction.

The following side effects occur frequently when using Xembify (may affect 1 or more in 100 people):

• headache;
• joint pain;
• back pain;
• rhinitis (cold, sneezing, and stuffy nose);
• diarrhea;
• nausea;
• fever;
• decreased immunoglobulin G levels in the blood;
• itching (itching);
• papular rash (small bumps on the skin surface)

Side effects reported after the product was placed on the market

After Xembify was placed on the market, the following side effects were identified and reported (none of them were serious): shortness of breath, fatigue, pain, nausea, headache, and infusion site reactions, such as redness and swelling.
A reliable estimate of the frequency of these reactions is not always possible.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, you should tell your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Post-Marketing Surveillance of Medicinal Products, Medical Devices, and Biocides, 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.
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Xembify

The medicine should be kept out of the sight and reach of children.

• Store in a refrigerator (2°C - 8°C).
  Xembify can be stored at a temperature not exceeding 25°C for a maximum of 6 months before the expiration date.
  On the day the product is removed from the refrigerator, the "removal date" should be written on the packaging, which is 6 months from the date of removal from the refrigerator or the expiration date printed on the packaging, whichever comes first.
  Xembify should not be returned to the refrigerator after storage at room temperature. The medicine should be used before the "removal date" or discarded.
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Administer as soon as possible after transferring Xembify from the vial to the syringe.

Do not use this medicine after the expiration date stated on the label and packaging.
Do not use this medicine if it is discolored, cloudy, contains sediment, or has been frozen.
Medicines should not be disposed of via wastewater or household waste. You should ask your pharmacist how to dispose of medicines that are no longer needed. This will help protect the environment.

6. Contents of the packaging 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% IgG1, 30% IgG2, 4.3% IgG3, and 3.2% IgG4. The drug contains a small amount of IgA (no more than 160 micrograms/ml).
• The other ingredients are: glycine (E 640), polysorbate 80 (E 433), and water for injections.

What Xembify looks like and contents of the packaging

Xembify is a solution for subcutaneous injection. The solution is clear to slightly opalescent and colorless, pale yellow, or light brown.
Xembify is packaged in a cardboard box containing a clear glass vial with a stopper, aluminum cap, plastic cap, and heat-shrinkable band, which ensures the integrity of the packaging.
Xembify is supplied in packs of:

• 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 Xembify vials and 1 patient information leaflet.
Not all pack sizes may be marketed.

Marketing authorization holder and manufacturer

Instituto Grifols, S.A.
c/Can Guasch, 2
08150 Parets del Valles
Barcelona, Spain

Date of last revision of the leaflet: 26.04.2024

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 Biocides,
www.urpl.gov.pl.