Xembify 200 mg/ml solution for subcutaneous injection

Package leaflet: Information for the user

Introduction

Package leaflet: Information for the patient

Xembify 200mg/ml subcutaneous injection solution

Normal human immunoglobulin (IgSC)

This medicinal product is subject to additional monitoring, which will allow for faster identification of new safety information. You can help by reporting any adverse reactions you may experience. Section 4 includes information on how to report these adverse reactions.

Read the entire leaflet carefully before starting to use this medicine, as it contains important information for you.

? Keep this leaflet, as you may need to read it again.

? If you have any questions, consult your doctor, pharmacist, or nurse.

? This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, since it may harm them.

? If you experience any adverse reactions, consult your doctor, pharmacist, or nurse, even if they are adverse reactions not listed in this leaflet. See section 4.

Leaflet contents

1. What Xembify is and what it is used for
2. What you need to know 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) to help your body fight infections.

Xembify contains immunoglobulins obtained from the plasma of healthy individuals. Immunoglobulins help combat infections caused by bacteria and viruses. The medicine works in exactly the same way as the immunoglobulins naturally present in human blood produced by the immune system.

What Xembify is used for

You are receiving Xembify because you have very low levels of immunoglobulins due to a medical condition called immunodeficiency. Xembify infusions increase immunoglobulin (antibody) levels, specifically immunoglobulin G (IgG), in your blood to normal levels.

This medicine is for adults, children and adolescents (0–18 years) who lack sufficient antibodies (replacement therapy):

1. Patients with primary immunodeficiency syndrome (PIS) with a congenital antibody deficiency.
2. Hypogammaglobulinaemia (a disease involving low levels of immunoglobulins in the blood) and recurrent bacterial infections in patients with chronic lymphocytic leukaemia (a blood cancer in which too many white blood cells are produced) in whom prophylactic antibiotics have not been effective.
3. Hypogammaglobulinaemia and recurrent bacterial infections in patients with multiple myeloma (a tumour formed by cells derived from bone marrow).

Hypogammaglobulinaemia in patients after stem cell transplantation (allogeneic haematopoietic 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 components of this medicine (listed in section 6);

? if you have previously had a severe allergic reaction (such as anaphylaxis) to human immunoglobulin;

? if you have antibodies against immunoglobulin A (IgA) in your blood. This may occur if you have 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).

Tell your doctor, pharmacist, or nurse before Xembify infusion if you have ever had any adverse reaction to immunoglobulin or any of its components.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting to use Xembify.

• Inform your doctor if you have a history of heart disease, vascular disease, blood clot in a blood vessel (such as stroke, heart attack, or pulmonary embolism), thick blood, diabetes mellitus, high blood pressure, a bleeding or coagulation disorder, or if you have been immobile for some time. Inform your doctor if you are taking estrogens, usually as contraceptives. You may have an increased risk of developing a blood clot after Xembify infusion. Contact your doctor immediately if you experience difficulty breathing; 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, neck stiffness, drowsiness, fever, extreme sensitivity to light, nausea, or vomiting. These adverse effects may occur hours or even a few days after Xembify infusion. You may have aseptic meningitis syndrome.
• Xembify may cause kidney problems, including renal failure. Inform your doctor if you have reduced kidney function.
• Xembify may interfere with certain blood tests (serological tests). Always inform your doctor that you are being treated with Xembify before undergoing a blood test.

Allergic reactions

Allergic reactions are rare. However, you may have an allergy to immunoglobulins without knowing it. Allergic reactions such as 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 may occasionally occur even if you have not previously had adverse reactions to immunoglobulins. Your risk of allergic reactions is higher if you have IgA deficiency with anti-IgA antibodies. Make sure to inform your doctor if you have IgA deficiency. Xembify contains a small amount of IgA, which may increase the risk of an allergic reaction. See section 4 of this leaflet (Possible side effects) for signs and symptoms of an allergic reaction.

Risk of transmission of diseases

Xembify is purified from plasma obtained from healthy donors. When biological medicines are administered, it is not possible to completely exclude the risk of infectious diseases due to pathogen transmission. However, for products prepared from human plasma, the risk of pathogen transmission is reduced by: (1) epidemiological monitoring of the donor population and selection of individual donors through medical interviews; (2) testing of individual donations and plasma pools for markers of viral infection; and (3) manufacturing procedures with demonstrated capacity to inactivate/eliminate pathogens.

Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of transmitting infections cannot be completely ruled out. This also applies to unknown or 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, and against non-enveloped viruses such as hepatitis A virus. The measures taken may have limited effectiveness against non-enveloped viruses such as parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections contained in the medicine are protective.

It is strongly recommended that each time a dose of this medicine is administered to you, the name and batch number of the medicine (shown on the label and on the box after Batch) be recorded to maintain a record of the batches used.

Children and adolescents

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

Other medicines and Xembify

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicine.

Always administer Xembify infusion separately, without mixing it with any other medicine.

If you are to be vaccinated, inform the doctor that you are being treated with Xembify. Xembify may interfere with certain vaccines (live virus vaccines) such as measles, mumps, rubella, and varicella. You may need to wait up to 3 months after receiving Xembify before being vaccinated. For the measles vaccine, you may need to wait up to 1 year.

These interactions apply to children, adults, and elderly individuals.

Pregnancy, breastfeeding, and fertility

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

Studies with Xembify have not been conducted in pregnant or breastfeeding women, and therefore your doctor or pharmacist will guide you. Clinical experience with immunoglobulins suggests that harmful effects on pregnancy, the fetus, or the baby are not expected. If you are breastfeeding, immunoglobulins contained in Xembify may also be present in breast milk. Therefore, they may protect your baby against certain infections. Clinical experience with immunoglobulins suggests that harmful effects on fertility are not expected.

Driving and use of machines

Your ability to drive and use machines may be affected by certain adverse reactions, such as dizziness, associated with Xembify. If you experience adverse reactions during treatment, wait until they resolve before driving or using machines.

3. How to use Xembify

Follow exactly the administration instructions for this medicine given by your doctor. If in doubt, consult your doctor again.

Xembify must be infused under the skin (subcutaneous or SC administration).

Your doctor or nurse will initiate treatment with Xembify. Do not begin treatment with Xembify at home until you have received complete instructions.

Dosage

Your doctor will determine the recommended dose and dosing schedule. Your doctor will calculate the correct dose for you based on your body weight, any previous treatment you have received, and your response to treatment. Follow exactly the administration instructions for the medicine contained in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, ask them.

Your first dose may be what is called a "loading dose," intended to rapidly increase immunoglobulin levels in your blood. Your doctor will determine whether you need a "loading dose" (for adults or children) of at least 1 to 2.5 ml/kg body weight. This loading dose may be administered over several days.

Xembify will be administered periodically, from daily to once every 2 weeks, with a cumulative monthly dose of approximately 1.5 to 5 ml/kg body weight. Your doctor may adjust the dose depending on your response to treatment.

Do not change this dose or the time interval until the next dose without first consulting your doctor.

If you think you should receive a different dose or wish to modify your dosing schedule, consult your doctor first. Contact your doctor if you forget to take a dose.

Routine blood tests will be required to measure the level of immunoglobulin in your blood. Discuss the schedule with your doctor.

There is no difference between the dosage for adults, including elderly people (65 years of age or older), and the dosage for children and infants, since the amount of Xembify infused is based on body weight.

Method of administration

You will receive Xembify via slow infusion under the skin into the fatty tissue (a subcutaneous infusion). Xembify will be administered using a pump or injector. Subcutaneous infusion for home treatment must be initiated and supervised by a healthcare professional experienced in training patients for home therapy.

You (or your caregiver) must receive training on:

• the use of an administration device, such as a syringe pump, if necessary,
• the use of aseptic infusion techniques (germ-free),
• maintaining a treatment diary, and
• recognizing and taking appropriate measures if serious adverse effects occur.

You must carefully follow your doctor's instructions regarding the dose, infusion rate, and infusion schedule of Xembify to ensure effective treatment.

Infusion sites

Administer Xembify only by the subcutaneous route. Infuse Xembify into the subcutaneous tissue at sites such as:

• the abdomen,
• the thighs,
• the upper arms, and
• the side of the hip.

When selecting infusion sites, avoid bony areas, visible blood vessels, scars, and any areas of inflammation (irritation) or infection. Rotate sites with each administration.

During your first two infusions, the infusion rate will start at 10 ml per hour per infusion site. If you do not experience adverse reactions (see section 4), the rate may be increased every 10 minutes up 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 2 infusion sessions, the infusion rate may be gradually increased up to 35 ml per hour per infusion site. Consult your doctor before increasing the infusion rate.

You may perform the infusion at more than one site simultaneously, provided the sites are separated by at least 5 cm. Adults may divide the dose among multiple sites, especially if the volume exceeds 30 ml. There is no limit to the number of sites you may use. You may use more than one pump to do so.

Instructions for use

Subcutaneous infusion for home treatment must be initiated and supervised by a healthcare professional experienced in training patients for home therapy. Suitable infusion pumps may be used for subcutaneous administration of immunoglobulins. The patient or caregiver must be trained in the use of an infusion pump, infusion techniques, maintenance of the treatment diary, and recognition and management of serious adverse reactions.

Follow the steps below and use an aseptic technique when administering Xembify.

Before use, allow the solution to reach room or body temperature (20–37°C). This may take 60 minutes or longer.

Do not apply heat or place it in a microwave.

Step 1: Preparation of materials

Gather the vial(s) of Xembify, ancillary materials, a sharps container, the patient treatment diary/record, and the infusion pump(s).

Step 2: Cleaning the surface

Set up your 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 wipe, using a circular motion from the center outward.

Step 3: Handwashing

Wash and dry your hands thoroughly before using Xembify.

Your doctor may recommend using antibacterial soap or wearing gloves.

Step 4: Checking 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 discolored. The solution should be clear to slightly opalescent and colorless or pale yellow or light brown.
• the protective cap is missing or there is evidence of tampering. Inform your doctor immediately.
• the expiration date has passed.

Step 5: Removing the protective cap

Remove the protective cap from the vial to expose the center of the stopper.

Clean the stopper with alcohol and allow it to dry.

Step 6: Transferring Xembify from the vial(s) to the syringe

Do not let your fingers or other objects touch the inner plunger rod, syringe tip, or other areas that may contact the Xembify solution. Ensure needles remain capped until use and that syringes and needles remain in the clean area established in Step 2. This is called "aseptic technique" to prevent germs from entering Xembify.

Using aseptic technique, attach each needle to the syringe tip.

Step 7: Preparing the syringe and drawing Xembify into the syringe

Remove the needle cap.

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 amount of air should equal the amount of Xembify to be withdrawn.

Invert the vial and withdraw the correct amount of Xembify. If multiple 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: Preparing the infusion pump

Follow the manufacturer's instructions for preparing the infusion pump, administration tubing, and Y-connector tubing, if needed.

Prime the administration tubing with Xembify to remove any air in the tubing or needle. To prime, hold the syringe in one hand and the needle with the tubing cap in the other. Gently press the plunger until a drop of Xembify appears at the needle tip.

Step 9: Selecting the number and location of infusion sites

Select one or more infusion sites as directed by your doctor.

The number and location of infusion sites depend on the total dose volume.

Suitable infusion sites are: the abdomen, thighs, upper arms, and side of the hip.

Avoid: bony areas, visible blood vessels, scars, and any areas of inflammation (irritation) or infection.

Rotate sites between future infusions.

Step 10: Preparing the infusion site

Clean the infusion site(s) with a sterile alcohol wipe, starting at the center of each site and moving outward in a circular motion. Allow the site(s) to dry (at least 30 seconds).

Before infusion, sites must be clean, dry, and at least 5 cm apart.

Step 11: Inserting the needle

Pinch the skin between two fingers (pinch at least 2.5 cm of skin) and insert the needle at a 90-degree angle into the tissue beneath the skin or subcutaneous tissue.

Step 12: Checking that the needle is not in a blood vessel

After inserting each needle into the tissue (and before infusion), ensure the needle has not accidentally entered a blood vessel. To do this, connect a sterile syringe to the primed end of the administration tubing. Pull back on the syringe plunger and observe whether blood enters the tubing.

If blood is seen, remove and discard the needle and administration tubing.

Repeat the priming and needle insertion steps using a new needle and administration tubing and a new infusion site.

Secure the needle in place by applying a sterile gauze or transparent dressing over the site.

Step 13: Repeat for other sites, as needed

Step 14: Infusing Xembify

Infuse Xembify as soon as possible after preparation.

Follow the manufacturer's instructions for filling the tubing and operating the infusion pump.

Step 15: After the infusion

Follow the manufacturer's instructions to turn off the pump.

Remove and discard any dressings or adhesive tape.

Carefully remove the inserted needle(s) or catheter(s).

Dispose of any unused solution in an appropriate waste container, as instructed.

Dispose of any used administration equipment in an appropriate waste container.

Store your materials in a safe place.

Follow the manufacturer's instructions for syringe pump maintenance.

Step 16: Recording each infusion

Remove the peel-off label with the product lot number from the Xembify vial and use it to complete the patient record. Include information about each infusion, such as:

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

Remember to bring your diary when visiting your doctor. Your doctor may ask you to show your treatment diary/record.

Inform your doctor of any problems you experience during your infusions. Call your doctor to report adverse effects.

Use in elderly patients

The dose for elderly patients is not considered different from that for patients aged 18 to 65 years.

Use in children and adolescents

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

If you use more Xembify than you should

Contact your doctor for instructions.

In case of overdose or accidental administration, contact your doctor or pharmacist immediately or call the Toxicology Information Service at telephone number 91 562 04 20, indicating the medicine and the amount administered.

If you forget to use Xembify

Do not take a double dose to make up for missed doses. Contact your doctor for instructions.

If you have any further questions about the use of this medicine, ask your doctor.

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Rarely, normal human immunoglobulins may cause a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has not shown hypersensitivity to previous administrations.

Signs or symptoms of these rare allergic reactions include:

• feeling dizzy, lightheaded, or fainting;
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing;
• irregular heartbeat, chest pain, bluish discoloration of the lips or fingers and toes.

If you notice any signs of an allergic or anaphylactic-type reaction during Xembify infusion, stop the infusion immediately and contact your doctor or go to the nearest hospital. See section 2 of this leaflet (Warnings and precautions). If you notice any of these signs during Xembify infusion when administered by a healthcare professional, inform your doctor or nurse immediately. They will decide whether to reduce the infusion rate or stop it completely.

Local reactions at the infusion site may occur, such as swelling, pain, redness, induration (hard lump), local warmth, itching, bruising, and skin rash.

Xembify may occasionally cause chills, headache, dizziness, fever, vomiting, allergic reactions, malaise (nausea), joint pain, low blood pressure, and moderate lower back pain.

The following adverse effects are very common with Xembify (may affect 1 or more people in 10):

? Local reaction at the infusion site

The following adverse effects are common with Xembify (may affect 1 or more people in 100):

? Headache

? Arthralgia (joint pain)

? Back pain

? Rhinitis (nasal discharge, sneezing, and congestion)

? Diarrhea

? Nausea

? Pyrexia (fever)

? Decrease in immunoglobulin G in blood

? Pruritus (itching)

? Papule (small raised area of skin)

Post-marketing adverse effects

The following adverse reactions have been identified and reported during post-marketing use of Xembify (none serious): dyspnea (difficulty breathing), fatigue, pain, nausea, headache, and local reaction at the infusion site, such as erythema (redness) and swelling. The frequency of these reactions cannot always be reliably estimated.

Reporting of adverse effects

If you experience any adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicinal Products: www.notificaRAM.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Xembify

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

• Store in a refrigerator (between 2°C and 8°C).

  o Xembify may be stored at temperatures not exceeding 25°C for up to 6 months at any time before the expiry date.

  o On the day the medicine is removed from the refrigerator, write in the "Date of disposal" space provided on the carton the date 6 months from that date or the expiry date printed on the carton flap, whichever comes first.

  o If stored at room temperature, do not return the medicine to the refrigerator. Use the medicine before the "Date of disposal" or discard it.

• Do not freeze.

• Keep 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 expiry date stated on the label and carton.

Do not use this medicine if you notice that it is discolored, cloudy, contains particles, or has been frozen.

Medicines must not be disposed of via wastewater or household waste. Dispose of empty containers and unused medicines at a SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of containers and medicines you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Xembify

? The active substance is human normal immunoglobulin (IgSC). One ml contains 200 mg of human normal immunoglobulin, of which at least 98% is IgG.

The percentage distribution of IgG subclasses is approximately 62% IgG1, 30% IgG2, 4.3% IgG3 and 3.2% IgG4. It contains a small amount of IgA (not more than 160 micrograms/ml).

? The other components are glycine (E 640), polysorbate 80 (E 433) and water for injections.

Appearance of the product and contents of the pack

Xembify is a subcutaneous injectable solution. The solution is transparent to slightly opalescent, and colourless or yellowish or light brown.

Xembify is supplied in a box and contained in a clear glass vial with a stopper, an aluminium seal, a plastic cap and a tamper-evident seal ensuring the integrity of the container.

Xembify is available in pack sizes of:

1 or 10 vials containing 1 g of human normal immunoglobulin in 5 ml of subcutaneous injectable solution

1, 10 or 20 vials containing 2 g of human normal immunoglobulin in 10 ml of subcutaneous injectable solution

1 or 20 vials containing 4 g of human normal immunoglobulin in 20 ml of subcutaneous injectable solution

1 or 10 vials containing 10 g of human normal immunoglobulin in 50 ml of subcutaneous injectable solution

Each box contains 1, 10 or 20 vials of Xembify and 1 package leaflet.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona - Spain

Date of the most recent revision of this leaflet: May 2024

Other sources of information

Detailed information on this medicinal product is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) (http://www.aemps.gob.es/)