Product Information for the User

HyQvia100mg/ml, Infusion Solution

Normal Human Immunoglobulin

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

• Keep this product information, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to otherseven if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even ifthey are not listed in this product information. See section4.

1.What is HyQvia and how is it used

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

3.How to use HyQvia

4.Possible adverse effects

5.Storage of HyQvia

6.Contents of the package and additional information

What is HyQvia

HyQvia contains 2 solutions for subcutaneous infusion (SC). It is supplied in a container that contains:a vial of normal human immunoglobulin 10% (the active ingredient)

• a vial of human recombinant hyaluronidase (a substance that helps the normal human immunoglobulin 10% reach the blood)

Normal human immunoglobulin 10% belongs to a class of medicines called “normal human immunoglobulins”. Immunoglobulins are also antibodies and are found in the blood of healthy individuals. Antibodies are part of the immune system (the body's natural defenses) and help the body fight infections.

How HyQvia works

The human recombinant hyaluronidase is a protein that facilitates the subcutaneous infusion of immunoglobulins and their arrival in the circulatory system.

The vial of immunoglobulins is prepared from the blood of healthy individuals. Immunoglobulins are produced by the human immune system. They help the body fight infections caused by bacteria and viruses or maintain immune system balance (known as immunomodulation). The medicine acts in the same way as naturally occurring immunoglobulins in the blood.

What is HyQvia used for

Substitution therapy in adults and children (0 to 18 years of age)

HyQvia is used in patients with a weakened immune system, who do not have enough antibodies in the blood and are prone to infections, including the following groups:

• patients born with an inability or reduced capacity to produce antibodies (primary immunodeficiencies),
• patients suffering from severe or recurrent infections due to a weakened immune system resulting from other conditions or treatments (secondary immunodeficiencies).

Regular and sufficient doses of HyQvia can increase abnormally low immunoglobulin levels in the blood to normal levels (substitution therapy).

Immunomodulatory therapy in adults, children, and adolescents (0 to 18 years of age)

Do not inject or infuse HyQvia

• if you are allergic to immunoglobulins, hyaluronidase, recombinant hyaluronidase, or any of the other components of this medication (listed in section 6, “Contents of the container and additional information”)
• if you have antibodies against immunoglobulin A (IgA) in your blood. This can occur if you have IgA deficiency. As HyQvia contains traces of IgA, you may experience an allergic reaction
• in a blood vessel (intravenously) or in a muscle (intramuscularly)

Warnings and precautions

Consult your doctor or nurse before starting to use HyQvia.

• You or your child may be allergic to immunoglobulins and not know it. Allergic reactions, such as a sudden drop in blood pressure or anaphylactic shock (a sudden drop in blood pressure along with other symptoms such as throat swelling, difficulty breathing, and skin rash), are rare but can occur even if you have not had problems with similar treatments before. You are at greater risk of experiencing allergic reactions if you have IgA deficiency with anti-IgA antibodies. The signs or symptoms of these rare allergic reactions include:

• dizziness, drowsiness, or loss of consciousness,
• skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing (a high-pitched sound that occurs when breathing),
• abnormal heart rate, chest pain, bluish discoloration of the lips or fingers and toes,
• blurred vision

Your doctor or nurse will infuse human recombinant hyaluronidase (HY) followed by immunoglobulin (Ig) slowly and carefully, and will monitor you during the first infusion to detect and treat any allergic reaction immediately.

• Your doctor will take extra care if you are overweight, are an elderly patient, have diabetes, have been bedridden for a prolonged period, have high blood pressure, have low blood volume (hypovolemia), have vascular problems (vascular diseases), have an increased tendency to blood clotting (thrombophilia or thrombotic episodes), or have a disease that makes your blood thicker (hyperviscous blood). In these circumstances, immunoglobulins may increase the risk of heart attack, stroke, pulmonary embolism, or blockage of a leg vein, although this is extremely rare.
• • If you notice any of these signs and symptoms during infusion, including shortness of breath, pain, swelling of a limb, and chest pain, inform your doctor or nurse immediately. They will decide whether to reduce the infusion rate or stop it completely.

Your doctor or nurse will closely monitor you during infusions to detect and treat any thromboembolic events immediately.

• You will receive this medication in high doses over 1 or 2 days, and in the case of blood groups A, B, or AB and underlying inflammatory disease. In these circumstances, immunoglobulins have been reported to increase the risk of red blood cell destruction (hemolysis).
• There have been reports of inflammation of the membranes surrounding the brain and spinal cord (aseptic meningitis syndrome) related to treatment with immunoglobulins.
• • If you notice any of these signs and symptoms after infusion, including severe headache, neck stiffness, dizziness, fever, photophobia, nausea, and vomiting, inform your doctor or nurse immediately.

Your doctor will decide whether to perform further tests and whether treatment with HyQvia should continue.

Infusion rate

It is very important to infuse the medication at the correct rate. Your doctor or nurse will advise you on the correct infusion rate for when you infuse HyQvia at home (see section 3, “How to use HyQvia”).

Monitoring during infusion

Determined adverse effects may occur more frequently if:

• you are receiving HyQvia for the first time
• you have received another immunoglobulin and switched to HyQvia
• you have been a long time (for example, more than 2 or 3 infusion intervals) since your last HyQvia infusion
• • In these cases, you will be closely monitored during the first infusion and during the first hour after the infusion has ended.

In other cases, you will be closely monitored during infusion and at least 20 minutes after you have received the first HyQvia infusions.

Home treatment

Before starting home treatment, you will be assigned a caregiver. You and your caregiver will be trained to detect the first signs of adverse effects, especially allergic reactions.This caregiver will help you observe any possible adverse effects. During infusion, you should observe if any of the first signs of adverse effects occur (for more details, see section 4, “Possible adverse effects”).

Spread of localized infections

Do not infuse HyQvia in or around an infected or swollen and red area of the skin, as this could spread the infection.

No long-term (chronic) skin changes were observed in clinical studies.You should inform your doctor of any long-term inflammation, lumps (nodules), or inflammation that appears at the infusion site and lasts more than a few days.

Effects on blood tests

HyQvia contains many different antibodies, some of which may interfere with blood tests (serological tests).

• Before a blood test, inform your doctor of your treatment with HyQvia.

Information about the material of origin of HyQvia

The human normal immunoglobulin 10% of HyQvia and the human serum albumin (a component of recombinant hyaluronidase) are produced from human plasma (the liquid part of blood). When medications are produced from blood or plasma, certain measures must be taken to prevent the possible transmission of infections to patients. These include:

• a careful selection of blood and plasma donors to ensure the exclusion of donors who are at risk of being carriers of infectious diseases
• analysis of each donation and plasma mixture to detect possible viruses or infections

The manufacturers of these products also include steps in the manufacturing process to eliminate/inactivate viruses.Despite this, when using medications derived from blood or plasma, the possibility of transmission of infectious agents cannot be completely ruled out. This also applies to emerging or unknown viruses and infectious agents.

The measures taken for the production of HyQvia are considered effective for enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for non-enveloped viruses such as hepatitis A and parvovirus B19.

Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infections, probably because the antibodies associated with these infections (and found in HyQvia) provide protection.

• It is strongly recommended that each time you receive a dose of HyQvia, the following data be recorded in your patient diary:

• the name of the product,
• the date of administration,
• the batch number of the medication, and
• the volume injected, the administration rate, the number and location of infusion sites.

Children and adolescents

Replacement therapy

The same indications, doses, and infusion frequencies for adults apply to children and adolescents (0 to 18 years).

Immunomodulatory therapy in patients with PDICin children and adolescents

The safety and efficacy of HyQvia have not been established in children and adolescents (0 to 18 years) with PDIC.

Other medications and HyQvia

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

Vaccines

HyQvia may reduce the effect of some vaccines, such as measles, mumps, rubella, and varicella (vaccines made with live viruses). Therefore, you may need to wait until 3 months after receiving HyQvia before receiving certain vaccines. You may need to wait until 1 year after receiving HyQvia before receiving the measles vaccine.

• Before vaccination, inform your doctor or nurse about your treatment with HyQvia.

Pregnancy, breastfeeding, and fertility

The data on the effects of long-term use of recombinant hyaluronidase on pregnancy, breastfeeding, and fertility are limited. HyQvia should only be used in pregnant women or breastfeeding women after consulting with your doctor.

Driving and operating machines

During treatment with HyQvia, patients may experience adverse effects (such as dizziness or nausea) that may affect their ability to drive and use machines.If this occurs, you should wait until the reactions have subsided.

HyQvia contains sodium

This medication contains 5.0 to 60.5 mg of sodium (the main component of table salt/for cooking) in each vial of recombinant hyaluronidase HyQvia. This is equivalent to between 0.25 and 3% of the recommended daily maximum sodium intake for an adult.

The Ig 10% component is essentially sodium-free.

Follow the exact administration instructions for this medication as indicated by your doctor. If in doubt, consult your doctor again.

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

Your doctor or nurse will initiate treatment with HyQvia, but once you have received the first infusions under medical supervision and you (and/or your caregiver) are properly trained, you can use the medication at home. You and your doctor will decide if you can use HyQvia at home. Do not start treatment with HyQvia at home until you have received complete instructions.

Dosage

Replacement therapy

Your doctor will calculate the correct dose based on your body weight, previous treatments you have received, and your response to treatment. The recommended starting dose is one that provides400to800mg of active ingredient per kg ofbody weight per month. Initially, you will receive a quarter ofthat dose at intervals of1week. Subsequent infusions will gradually increase to higher doses at intervals of3to4weeks. Sometimes, your doctor may recommend dividing larger doses and administering them at 2 points at a time. Your doctor may also adjust the dose based on your response to treatment.

Immunomodulatory therapy

Your doctor will calculate the correct dose for you based on previous treatments you have received and your response to treatment. Normally, treatment begins1or2weeks after the last subcutaneous infusion of immunoglobulin administered. Your healthcare professional may adjust the dose and frequency based on your response to treatment.

If you exceed the daily dose (>120g) or if you cannot tolerate the volume of immunoglobulin infusions, the dose can be divided and administered over several days, leaving between48and72hours between doses to allow for proper absorption; the administration of hyaluronidase must also be divided appropriately.

Starting treatment

Treatment will be initiated by a doctor or nurse with experience in treating patients with a weakened immune system (immunodeficiency) and PDIC, training patients for home treatment. You will be closely monitored during the infusion and for at least1hour after to see if you tolerate the medication well. Initially, your doctor or nurse will use a slow infusion rate and gradually increase it during the first infusion and subsequent infusions. Once your doctor or nurse has found the correct dose and infusion rate for you, you can administer the treatment at home.

Home treatment

Do not use HyQvia at home until you receive instructions and training from a healthcare professional.

You will be trained in:

• Asptic (germ-free) infusion techniques,
• The use of an infusion pump or continuous infusion pump (if necessary),
• Maintaining a patient diary, and
• Measures to be taken in case of severe adverse reactions.

You must carefully follow your doctor's instructions regarding dose, infusion rate, and scheduling when administering HyQvia to ensure the treatment works properly.

The following infusion rates are recommended for Ig10% per infusion site:

The recommended infusion rates are for a single infusion site. If the patient needs 2 or 3 infusion sites, the infusion rates may be adjusted accordingly (i.e., doubled or tripled in accordance with the maximum infusion rate of the pump).

If a loss occurs at the infusion site

Ask your doctor, pharmacist, or nurse if a different needle size would be more suitable for you. Any change in needle size must be supervised by your doctor.

If you use more HyQvia than you should

If you think you have used more HyQvia than you should, consult your doctor as soon as possible.

If you forget to use HyQvia

Do not administer a double dose of HyQvia to compensate for missed doses. If you think you have missed a dose, consult your doctor as soon as possible.

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

Instructions for use are provided in the following section.

Like all medicines, this medicine can cause side effects, although not everyone will experience them. Some side effects, such as headache, chills, or body aches, can be reduced by decreasing the infusion rate.

Severe side effects

The infusion of medicines like HyQvia, on occasion, may cause severe allergic reactions, although they are rare. You may experience a sudden drop in blood pressure and, in isolated cases, anaphylactic shock. Doctors are aware of these possible side effects and will monitor you during and after the initial infusions.theywillcontrolthem

The typical signs or symptoms include:

dizziness, drowsiness, or loss of consciousness, skin rash and itching, swelling of the mouth or throat, difficulty breathing, wheezing (a high-pitched sound when breathing), abnormal heart rate, chest pain, blue discoloration of the lips or fingers and toes, blurred vision.

• If you notice any of the following signs during the infusion, inform your doctor or nurse immediately.
• When using HyQvia at home, you should perform the infusion in the presence of an assigned caregiver who will help you monitor allergic reactions, stop the infusion, and seek help if necessary.
• Also, see section2of this leaflet about the risk of allergic reactions andthe use of HyQvia at home.

Very common side effects (may occur in more than1of every10infusions):

Local reactions at the infusion site (including all the following points of infusion). These reactions usually disappear in a few days.

Common side effects (may occur in up to1of every10infusions):

• headache
• nausea
• abdominal pain/abdominal tenderness
• skin redness (erythema)
• reactions at the infusion site, including pain, discomfort, tenderness, redness, swelling, and itching
• sensation of heat,fever
• weakness (asthenia), fatigue, lack of energy (lethargy), and general feeling of discomfort

Uncommon side effects (may occur in up to1of every100infusions):

• dizziness
• migraine
• sensations of numbness, tingling, and pins and needles (paresthesia)
• shaking
• rapid heart rate (tachycardia)
• high blood pressure (hypertension)
• swelling of the stomach (abdominal distension)
• diarrhea
• vomiting
• skin rash
• itching (pruritus)
• skin rash with itching (urticaria)
• muscle pain (myalgia)
• joint pain (arthralgia)
• back pain
• pain in the limbs (including limb discomfort)
• chest wall musculoskeletal pain
• joint stiffness
• reactions at the infusion site (such as color change, bruising, redness [hematoma], bleeding [hemorrhage], puncture of the blood vessel, mass [nodule], induration, swelling [edema], chills, burning sensation, skin rash)
• genital swelling

• Rare side effects (may occur in up to 1 in every1000infusions):

• stroke
• low blood pressure (hypotension)
• difficulty breathing (dyspnea)
• inguinal pain
• brown urine (hemosiderinuria)
• excessive sweating (hyperhidrosis)
• inflammation of the infusion site
• heat at the infusion site
• sensations of numbness, tingling, and pins and needles at the infusion site (paresthesia at the infusion site)
• positive Coombs test result

Frequency not known (cannot be estimated from available data):

• inflammation of the membranes surrounding the brain and spinal cord (aseptic meningitis)
• allergic reactions (hypersensitivity)
• loss at the infusion site
• pseudogripal syndrome (gripal disease)

Reporting of side effects

If you experienceany type ofside effect, consult your doctor, pharmacist, or nurse, even if it is apossibleside effect 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 side effects, you can contribute to providing more information about the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the label and the box after CAD. The expiration date is the last day of the month indicated.

Store in refrigerator (between 2°C - 8°C). Do not freeze.

Do not shake.

Store the vials in the outer packaging to protect them from light.

Do not use this medication if you observe that the solutions have a turbid appearance or if they have particles or sediments.

Dispose of any unused solution from the vials after opening.

Medicines should not be thrown away through drains or in the trash. Ask your pharmacist how to dispose of the packaging and the medications that you no longer need. In this way, you will help protect the environment.

Composition of HyQvia

HyQvia is a dual vial unit that contains:

• a human recombinant hyaluronidase solution (Step 1 of HyQvia/Infuse first) and
• a 10% human normal immunoglobulin solution (Step 2 of HyQvia/Infuse second).

The content ofeach vialis described below:

1.Hyaluronidase human recombinant

This vial contains human recombinant hyaluronidase.

The other components are sodium chloride, sodium phosphate, human albumin, disodium ethylenediaminetetraacetic acid (EDTA), calcium chloride, and water for injection (see also section 2, “HyQvia contains sodium”).

2.Human normal immunoglobulin 10%

One ml of the solution in this vial contains100mg of human normal immunoglobulin of which, at least, the98% is immunoglobulin G (IgG).

Theactive principleof HyQvia is human normal immunoglobulin. This medicine contains tracesof immunoglobulin A (IgA) (no more than140micrograms/ml,37micrograms of mean).

The other components of this vial are glycine and water for injection.

Appearance of the product and contents of the pack

HyQvia 100mg/ml solution for subcutaneous infusion (infusion under the skin).

HyQvia is supplied in a pack that contains:

• a glass vial of human recombinant hyaluronidase and
• a glass vial of human normal immunoglobulin 10%.

The human recombinant hyaluronidase is a transparent and colourless solution.

The human normal immunoglobulin 10% is a transparent and colourless or slightly yellowish solution.

The following pack sizes are available:

Only some pack sizes may be marketed.

Marketing authorisation holder andresponsible person for manufacturing

Marketing authorisation holder:

Baxalta Innovations GmbH

Industriestrasse67

A‑1221Viena

Austria

Responsible person for manufacturing:

Baxalta Belgium Manufacturing SA

Boulevard René Branquart80

B‑7860Lessines

Belgium

For further information about this medicinal product, please contact the local representative of the marketing authorisation holder:

Takeda Farmacéutica España, S.A

Tel: +34 917 90 42 22

[email protected]

Last update of this leaflet: 05/2024.

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agency:http://www.ema.europa.eu