Prospect: Information for the Patient

Xembify 200mg/ml subcutaneous injectable solution

Normal human immunoglobulin (IgSC)

This medicine is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this prospect carefully before starting to use this medicine, because it contains important information for you.

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

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

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

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

1.What is Xembify and what is it used for

2.What you need to know before starting to use Xembify

3.How to use Xembify

4.Possible adverse effects

5.Storage of Xembify

6.Contents of the package and additional information

What is Xembify

Xembify is a solution of human immunoglobulins (antibodies, primarily immunoglobulinG) to help your body fight infections.

Xembify contains immunoglobulins derived from the plasma of healthy individuals. Immunoglobulins help combat infections caused by bacteria and viruses. The medication works exactly like the naturally occurring immunoglobulins present in human blood produced by the immune system.

How is Xembify used

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

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

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

Hypogammaglobulinemia in patients after an allogeneic hematopoietic stem cell transplant (AHCT), when receiving stem cells from another person.

No use Xembify

?if you are allergic to human normal immunoglobulin or to any of the other components of this medication (listed in section6);

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

?if you have antibodies against human immunoglobulin A (IgA) in your blood. This can occur if you have an IgA deficiency. Since Xembify contains IgA, you may have an allergic reaction;

?by injection into a vein (intravenous) or into a muscle (intramuscular).

Inform your doctor, pharmacist, or nurse before the infusion of Xembify if you have ever had any adverse effect from an immunoglobulin or any of its components.

Warnings and precautions

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

• Inform your doctor if you have a history of heart disease, vascular disease, a blood clot in a blood vessel (such as a stroke, heart attack, or pulmonary embolism), thick blood, diabetes mellitus, high blood pressure, a bleeding or clotting disorder, or if you have been immobile for some time. Inform your doctor if you are taking estrogen, usually as a contraceptive. You may have a higher risk of developing a blood clot after the infusion of Xembify. Contact your doctor immediately if you experience difficulty breathing; chest pain; pain and swelling in an arm or leg; or weakness or numbness in 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 appear hours or even days after the infusion of Xembify. You may develop aseptic meningitis syndrome.
• Xembify may cause kidney problems, including renal insufficiency. Inform your doctor if you have reduced renal function.
• Xembify may interfere with certain blood tests (serological tests). Always inform your doctor that you are being treated with Xembify before a blood test is performed.

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 (sudden drop in blood pressure with other symptoms such as throat swelling, difficulty breathing, and skin rash) are rare, but may occur occasionally even if you have not had adverse effects from immunoglobulins in the past. You have a higher risk of suffering allergic reactions if you have an IgA deficiency with anti-IgA antibodies. Ensure that you inform your doctor if you have an IgA deficiency. Xembify contains some amount of IgA that may increase the risk of an allergic reaction.See section4 of this prospectus (Possible adverse effects) to know the signs and symptoms of an allergic reaction.

Risk of disease transmission

Xembify is purified from human plasma obtained from healthy donors. When biologic medications are administered, it cannot be entirely ruled out that infectious diseases may occur due to the transmission of pathogens. However, in the case of products prepared from human plasma, the risk of transmission of pathogens is reduced by: (1) epidemiological controls of the donor population and selection of individual donors through a medical interview; (2) analysis of individual donations and plasma mixtures to detect markers of viral infection; and (3) manufacturing procedures with demonstrated capability to inactivate/eliminate pathogens.

Despite these measures, when biologic medications are administered, it cannot be entirely ruled out that transmission of infections may occur. This also applies to unknown or 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, and for non-enveloped viruses such as hepatitis A virus. The measures taken may have limited value 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 medication, are protective.

It is strongly recommended that each time you are administered a dose of this medication, you note the name and batch number of the medication (which appears on the label and on the box after Lot) to keep a record of the batches used.

Children and adolescents

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

Other medications and Xembify

Inform your doctor or pharmacist if you are taking, have taken recentlyor may have to take any other medication.

Administer the Xembify infusion only, without mixing it with any other medication.

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

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 intend to become pregnant, consult your doctor or pharmacist before using this medication.

No studies have been conducted with Xembify in pregnant women or breastfeeding women, and therefore your doctor or pharmacist will guide you. Clinical experience with immunoglobulins suggests that no adverse effects are expected in pregnancy, in the fetus, or in the baby. If you are breastfeeding, the immunoglobulins contained in Xembify may also be found in breast milk. Therefore, they may protect your baby from certain infections. Clinical experience with immunoglobulins suggests that no adverse effects are expected in fertility.

Driving and operating machinery

Your ability to drive and operate machinery may be affected by some adverse reactions, such as dizziness, associated with Xembify. If you experience adverse reactions during treatment, wait until they disappear before driving or operating machinery.

Follow the exact administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.Consulte a su médico si tiene alguna duda sobre el uso de este medicamento.

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

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

Dosage

Your doctor will determine the recommended dosage and administration 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 the administration instructions for the medication contained in this leaflet or as indicated by your doctor, pharmacist, or nurse. If in doubt, ask them.

Your first dose may be a "loading dose," which aims to rapidly increase the levels of immunoglobulin in your blood. Your doctor will determine if you need a "loading dose" (for adults or children) of at least 1 to 2.5ml/kg of body weight. You may receive this loading dose divided over several days.

You will be administered Xembify periodically, from daily to once every 2 weeks; the accumulated dose per month will be approximately 1.5 to 5ml/kg of body weight. Your doctor may adjust the dose based on your response to treatment.

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

If you think you need a different dose or want to modify your administration schedule, consult your doctor before. Contact your doctor if you forget to take a dose.

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

There is no difference between the dose for adults, including those aged 65years or older, and the dose for children and infants, as the amount of Xembify infused is based on body weight.

Administration Form

You will receive Xembify through a slow infusion under the skin in the fatty tissue (a subcutaneous infusion). Xembify will be administered through a pump or injector. The subcutaneous infusion for home treatment must be initiated and supervised by a healthcare professional with experience in guiding patients for home treatment.

You (or your caregiver) must receive training on:

• using a delivery device, such as a syringe pump, if necessary,
• using aseptic infusion techniques (germ-free),
• maintaining a treatment diary, and
• recognizing and taking measures in case of severe adverse effects.

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

Infusion Sites

Administer Xembify only subcutaneously.Infuse Xembify in the subcutaneous tissue in areas such as

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

When selecting infusion sites, avoid: bony areas, visible blood vessels, scars, and any area of inflammation (irritation) or infection. Alternate sites between future infusions.

In your first two infusions, start with an infusion rate of 10 ml per hour per infusion site. If you do not experience adverse reactions (see section 4), you can increase the rate every 10 minutes to a maximum of 20 ml per hour per infusion site in children and adolescents and 25ml per hour per infusion site in adults. After 2infusion sessions, the infusion rate can be gradually increased to 35ml per hour per infusion site. Consult your doctor before increasing the infusion rate.

You can perform the infusion simultaneously in more than one site as long as they are separated by at least 5cm. Adults can divide the dose between several sites, especially if the volume is greater than 30ml. There is no limit to the number of sites you can use. You can use more than one pump to do so.

Usage Instructions

The subcutaneous infusion for home treatment must be initiated and supervised by a healthcare professional with experience in guiding patients for home treatment. Suitable infusion pumps can be used for the subcutaneous administration of immunoglobulins. The patient or caregiver must receive training on the use of a pump, infusion techniques, maintaining a treatment diary, recognizing, and taking measures in case of severe adverse effects.

Follow these steps and use aseptic technique to administer Xembify.

Before using, let the solution reach room temperature or body temperature (20-37°C). This may take 60minutes or more.

Do not apply heat or put it in the microwave.

Step1: Preparation of Materials

Gather the (the) vial(s) of Xembify, the complementary materials, the container for sharp objects, the patient's treatment diary/record, and the (the) infusion pump(s).

Step2: Cleaning the Surface

Set up your infusion site on a clean, flat, and non-porous surface, such as the kitchen countertop.

Avoid using porous surfaces like wood. Clean the surface with an alcohol wipe, moving in a circular motion from the center outwards.

Step3: Hand Washing

Wash and dry your hands before using Xembify.

Your doctor may recommend using an antibacterial soap or wearing gloves.

Step4: Checking the Vials

The liquid in the vial should be transparent to slightly opalescent, and colorless or pale yellow to light brown.

Do not use the vial if:

• the solution is cloudy or discolored. The solution should be transparent to slightly opalescent, and colorless or pale yellow to light brown.
• the protective closure cap is missing or there is evidence of manipulation. Inform your doctor immediately.

• the expiration date has passed.

Step5: Removing the Protective Closure Cap

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

Clean the stopper with alcohol and let it dry.

Step6: Transferring Xembify from the Vial to the Syringe

Do not let your fingers or other objects touch the internal plunger, the syringe tip, or other areas that may come into contact with the Xembify solution. Make sure the needles carry the cap until use and that the needles and syringes remain in the clean area created in step2. This is called "aseptic technique" to prevent germs from entering Xembify.

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

Step7: Preparing the Syringe and Extracting the Xembify Solution from the Syringe

Remove the cap from the needle.

Pull the syringe plunger back to the level corresponding to the amount of Xembify to be extracted from the vial.

Place the Xembify vial on a flat and clean surface and insert the needle into the center of the stopper.

Inject air into the vial. The amount of air should match the amount of Xembify to be extracted.

Invert the vial and extract the correct amount of Xembify. If multiple vials are needed to obtain the correct dose, repeat steps4-7.

Administer immediately after transferring Xembify from the vial to a syringe.

Step8: Preparing the Infusion Pump

Follow the manufacturer's instructions to prepare the infusion pump, the administration tube, and the Y-connector, if necessary.

Prime the administration tube with Xembify to eliminate any air remaining in the tube or needle. To prime, hold the syringe in one hand and the needle with the cap on the administration tube in the other. Gently press the plunger until you see a drop of Xembify from the needle.

Step9: Selecting the Number and Location of Infusion Sites

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

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

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

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

Alternate sites between future infusions.

Step10: Preparing the Infusion Site

Clean the (the) infusion site(s) with an alcohol wipe, starting from the center of each infusion site and moving outwards in a circular motion. Let the (the) infusion site(s) dry (at least 30seconds).

Before infusion, the sites must be clean, dry, and separated by at least 5cm.

Step11: Inserting the Needle

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

Step12: Checking that the Needle is Not in a Blood Vessel

After inserting each needle into the tissue (and before infusion), make sure it has not accidentally entered a blood vessel. To do this, connect a sterile syringe to the end of the administration tube that has been primed. Pull the syringe plunger back and observe if blood enters the administration tube.

If you see blood, remove and discard the needle and administration tube.

Repeat the steps of priming and inserting the needle using a new needle and administration tube, and a new infusion site.

Securetheneedle in place by applying a sterile gauze or transparent dressing.

Step13: Repeating for Other Sites, if Necessary

Step14: Infusing Xembify

Infuse Xembify as soon as possible after preparation.

Follow the manufacturer's instructions to fill the tube and use the infusion pump.

Step15: After Infusion

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

Remove and discard any dressing or adhesive tape.

Remove the needle or catheter carefully.

Dispose of any unused solution in an appropriate waste container, according to the instructions.

Dispose of any used equipment in an appropriate waste container.

Store your materials safely.

Follow the manufacturer's instructions for caring for the syringe pump.

Step16: Recording Each Infusion

Remove the removable label with the batch number from the Xembify vial and use it to complete the patient's record. Include information about each infusion, such as:

• the time and date,
• the dose,
• the batch number(s),
• the infusion sites, and
• any reaction.

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

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

Use in Elderly Patients

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

Use in Children and Adolescents

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

Using More Xembify than You Should

Contact your doctor for instructions.

In case of overdose or accidental administration, consult your doctor or pharmacist immediately or call the Toxicology Information Service, tel. 91 562 04 20, indicating the medication and the amount administered.

Forgetting to Use Xembify

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

If you have any other questions about using this medication, ask your doctor.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

In rare cases, 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 previous administration.

The signs or symptoms of these rare allergic reactions include:

• dizziness, dizziness, or fainting;
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing while breathing;
• abnormal heart rhythm, chest pain, bluish discoloration of the lips or fingers of the hands and feet.

If you observe any sign of allergic reaction or anaphylactic type during the infusion of Xembify,immediately stop the infusion and contact your doctor or go to the nearest hospital. See section2 of this leaflet (Warnings and precautions).If you observe any of these signs during the infusion of Xembify when administered by a healthcare professional,inform your doctor or nurse immediately. They will decide whether to reduce the infusion speed or suspend it completely.

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

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

The following side effects are very common with Xembify (may affect1 or more people in every10):

?Local reaction at the infusion site

The following side effects are common with Xembify (may affect1 or more people in every100):

?Headache

?Arthralgia (joint pain)

?Back pain

?Rhinitis (nasal secretion, sneezing, and congestion)

?Diarrhea

?Nausea

?Fever

?Decreased immunoglobulin G in blood

?Pruritus (itching)

?Papule (small elevated area of skin)

Post-marketing adverse reactions

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. It is not always possible to estimate the frequency of these reactions reliably.

Reporting of adverse reactions

If you experience any type of adverse reaction, consult your doctor, pharmacist, or nurse,even if it is a possible adverse reaction that does not appear in this leaflet.You can also report them directly through the Spanish System for Pharmacovigilance of Medicines for Human Use:www.notificaRAM.es.

By reporting adverse reactions, you can contribute to providing more information on the safety of this medicine.

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

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

orXembify can be stored at temperatures not exceeding 25°C for a maximum of 6months at any time before the expiration date.

orThe day the medication is taken out of the refrigerator, write in the space “Date of disposal” provided on the box the date of 6months after that moment or the expiration date printed on the label of the box, whichever is earlier.

orIf stored at room temperature, do not put the medication back in the refrigerator. Use the medication before the “Date of disposal” or discard it.

•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 medication after the expiration date that appears on the label and the box.

Do not use this medication if you observe that it is discolored, cloudy, has sediment, or has frozen.

Medications should not be disposed of through drains or trash.Deposit the containers and medications you no longer need at the SIGREpoint of the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Xembify

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

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

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

Appearance of the product and contents of the package

Xembify is a subcutaneous injectable solution. The solution is transparent to slightly opalescent, and colorless or pale yellow or light brown.

Xembify is presented in a box and is contained in a transparent glass vial with a stopper, an aluminum cap, a plastic cap, and a security seal that guarantee the integrity of the package.

Xembify is presented in packaging sizes of

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

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

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

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

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

Only some packaging sizes may be commercially marketed.

Marketing authorization holder and manufacturer responsible

Instituto Grifols, S.A.

Can Guasc, 2 - Parets del Vallès

08150 Barcelona - Spain

Last review date of this prospectus: May 2024

Other sources of information

The detailed information on this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) (http://www.aemps.gob.es/)