Prospecto: information for the user

Hizentra 200 mg/ml subcutaneous injectable solution

human normal immunoglobulin (IgSC =ImmunoglobulinSubcutaneous)

Read this prospectus carefully before starting to use this medication, as it contains important information for you.

• Keep this prospectus, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only for you and should not be given to other people, even if they present the same symptoms of disease as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospectus. See section 4.

1. What is Hizentra and for what it is used

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

3. How to use Hizentra

4. Possible adverse effects

5. Storage of Hizentra

6. Contents of the package and additional information

What is Hizentra

Hizentra belongs to a class of medications called human normal immunoglobulins. Immunoglobulins are also known as antibodies and are blood proteins that help the body fight infections.

How Hizentra works

Hizentra contains immunoglobulins that have been obtained from the blood of healthy individuals. Immunoglobulins are produced by the body's immune system. They help the body fight infections caused by bacteria and viruses or maintain balance in the immune system (known as immunomodulation). The medication works exactly like the immunoglobulins naturally present in the blood.

What is Hizentra used for

Substitution therapy

Hizentra is used to elevate abnormally low levels of immunoglobulin in the blood to normal levels (substitution therapy). The medication is used in adults and children (0-18 years) in the following situations:

1. Treatment of patients born with a reduced or inability to produceimmunoglobulins (primary immunodeficiencies). This includes conditions such as:

• Low levels of immunoglobulin (hypogammaglobulinemia) or absence of immunoglobulins in the blood (agammaglobulinemia)
• Combination of low levels of immunoglobulins, frequent infections, and inability to produce adequate levels of antibodies after vaccination (common variable immunodeficiency)
• Combination of low or absent levels of immunoglobulins, and absence or non-functionality of immune cells (severe combined immunodeficiency)
• Lack of certain subclasses of immunoglobulin G that cause recurrent infections.

1. Treatment of patients with low or dysfunctional levels of immunoglobulin in acquired conditions (secondary immunodeficiency) who experience severe or recurrent infections due to a weakened immune system as a result of other conditions or treatments.

Immunomodulatory therapy in patients with CIDP

Hizentra is also used in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), a type of autoimmune disease. CIDP is characterized by chronic inflammation of peripheral nerves that cause muscle weakness and/or numbness mainly in legs and arms. It is believed that the body's defenses exacerbate this inflammation, and Hizentra's immunoglobulins help protect the nerves from the attack (immunomodulatory therapy).

No to inject Hizentra:

• If you are allergic to human immunoglobulins, polysorbate 80, or L-proline.
• Inform your doctor or healthcare professional before treatment if you have had any intolerance to any of these components previously.
• If you have hyperprolinemia (a genetic disorder caused by the presence in the blood of high levels of the amino acid proline).

In blood vessels.

Warnings and precautions

• Consult your doctor, pharmacist, or nurse before using Hizentra.

You may be allergic (hypersensitive) to immunoglobulins without knowing it. However, true allergic reactions are rare. They can occur even if you have received human immunoglobulins previously and have tolerated them well. This can happen especially if you do not have enough of the immunoglobulin type A (IgA) in your blood (IgA deficiency).

• Inform your doctor or healthcare professional if you have an IgA deficiency before starting treatment. Hizentra contains residual amounts of IgA that may cause allergic reactions.

In rare cases, anaphylactic reactions may occur, such as a sudden drop in blood pressure or ashock(see also section 4. "Possible side effects").

• If you experience symptoms of this type during Hizentra perfusion, stop perfusion and contact your doctor or go to the nearest hospital immediately.

• Inform your doctor if you have a history of heart or vascular disease, or if you have experienced blood clot formation, have blood that is too thick, or have been immobile for some time. These factors may increase your risk of developing a blood clot after taking Hizentra. Also, inform your doctor about any medications you are taking, as some contain estrogens (a hormone found, for example, in birth control pills) that may increase your risk of developing a blood clot. Contact your doctor immediately if you experience symptoms such as difficulty breathing, chest pain, pain and inflammation of an extremity, weakness or numbness on one side of the body after taking Hizentra.

• Contact your doctor if you experience the following symptoms: sudden headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting after taking Hizentra. Your doctor will decide if further tests are necessary and if you should continue taking Hizentra.

Your healthcare professional will avoid possible complications by checking that:

• You are not sensitive to normal human immunoglobulin.

The product must be injected at a slow initial rate. The recommended injection rate must be strictly respected in the section 3 “How to use Hizentra”.

• Close monitoring of the presence of any symptoms during the entire perfusion period, especially if:

You are receiving Hizentra for the first time.

You have changed treatment with another medication.

More than eight weeks have passed since your last perfusion.

In these cases, you should be observed during the first perfusion and for one hour after it. If the above points do not apply to you, it is recommended that you be observed for at least 20 minutes after administration.

Hizentra interactions with other medications

• Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication.
• Do not mix Hizentra with other medications.
• Inform your doctor before vaccination about your treatment with Hizentra.

Hizentra may alter the effect of some live virus vaccines such as the measles, mumps, parotitis, and varicella vaccine. Therefore, wait at least 3 months after administration of these medications before receiving a live attenuated vaccine. In the case of the measles vaccine, this alteration may persist for up to 1 year.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, or if you think you may be pregnant or plan to become pregnant, inform your doctor or pharmacist. Your doctor will decide if you can receive Hizentra during pregnancy or while breastfeeding.

No studies have been conducted with Hizentra in pregnant women. However, immunoglobulin-containing medications have been used in pregnant women or breastfeeding women for years, and no adverse effects have been observed during pregnancy or in the baby.

If you are breastfeeding and receive Hizentra, the immunoglobulins in the medication may also be found in breast milk. Therefore, your baby may be protected against some infections.

Driving and operating machinery

During treatment with Hizentra, patients may experience effects such as dizziness or nausea that may affect their ability to drive and operate machinery. If this happens, do not drive or operate machinery until these effects have disappeared.

Hizentra contains proline

Do not take this medication if you have hyperprolinemia (see also section 2 “What you need to know before starting to use Hizentra”). Inform your doctor before treatment.

Other important information about Hizentra

Blood tests

After receiving Hizentra, the results of some blood tests (serological tests) may be altered for some time.

• Inform your doctor about your treatment with Hizentra before any blood test.

Information about Hizentra components

Hizentra is made from human blood plasma (this is the liquid part of the blood). When medications are made from blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These measures include:

• A meticulous selection of blood or plasma donors to ensure the exclusion of possible carriers of infections,and
• The examination of each donation and plasma mixtures to check for the absence of signs of viruses or infections.

Manufacturers of these medications also include steps in the processing of blood or plasma that may inactivate or eliminate viruses. Despite these measures, administering medications prepared from blood or plasma may not completely exclude the possibility of transmitting an infection. This is also true for any unknown or emerging virus, or any other type of infection.

The measures taken are considered effective for enveloped viruses such as the human immunodeficiency virus (HIV, the virus that causes AIDS), hepatitis B virus, and hepatitis C virus (inflammation of the liver), and for non-enveloped viruses such as hepatitis A virus and parvovirus B19.

• It is strongly recommended that each time you receive a dose of Hizentra, you note the name and batch number of the product, in order to keep a record of the batches used (see section 3, “How to use Hizentra”).

Hizentra contains sodium

This medication contains less than 23 mg of sodium (1 mmol) per vial/needle; this is, essentially “sodium-free”.

Follow exactly the administration instructions of this medication as indicated by your doctor. Consult your doctor if you have any doubts.

Dose

Your doctor will decide how much Hizentra you will receive, based on your weight and response to treatment.

The dose or administration interval should not be changed without consulting your doctor.

If you think you should receive Hizentra more or less frequently, please consult your doctor. If you think you have forgotten a dose, please speak with your doctor as soon as possible.

Substitution therapy

Your doctor will determine if you need a loading dose (for adults and children) of at least 1 to 2.5 ml/kg of body weight divided over several days. After that, maintenance doses will be administered at repeated intervals, from once a day to once every two weeks, to achieve a monthly cumulative dose of between 2 and 4 ml/kg of body weight. Your healthcare professional may adjust the dose based on your response to treatment.

Immunomodulatory therapy

Your doctor will start the therapy with Hizentra one week after your last intravenous infusion of immunoglobulin by administering it under the skin (subcutaneously) with a weekly dose of 1.0 to 2.0 ml/kg of body weight. Your doctor will determine your weekly dose of Hizentra. The weekly maintenance doses can be divided into smaller doses and administered at the required frequency during the week. For every two-week regimen, your doctor will double the weekly dose of Hizentra. Your healthcare professional may adjust the dose based on your response to treatment.

Form and route of administration

In the case of home treatment, it should be initiated by a healthcare professional with experience in the treatment of immunodeficiency/PDIC with IgSC and in instructing patients for home treatment.

You will be instructed and trained in:

• aseptic infusion techniques,
• the maintenance of a treatment diary, and
• measures to take in case of severe adverse effects.

Infusion points

• Administer Hizentra only subcutaneously.
• You can infuse Hizentra at points such as the abdomen, thigh, arm, and lateral hip. For high doses (> 50 ml), administer in multiple points.
• You can use an unlimited number of injection points simultaneously. The points where injections are applied should be at least 5 cm apart.
• If you use assisted infusion device technology (e.g., pump-assisted infusion),you can use multiple infusion devices simultaneously.
• If you use manual push infusion with a syringe, you can use only one infusion site per syringe. If you need to administer an additional syringe of Hizentra, you must use a new sterile injection needle and change the infusion site.
• The volume of product infused at a given site may vary.

Infusion rates

Your doctor will determine the appropriate infusion technique and infusion rate for you, taking into account your individual dose, dosing frequency, and product tolerability.

Device-assisted infusion:

The recommended initial infusion rate is up to 20 ml/hour per site. If well tolerated, the infusion rate can be gradually increased to 35 ml/hour per site for the two subsequent infusions.Thereafter, the infusion rate can be increased based on your tolerability.

Manual push infusion:

The recommended initial infusion rate is up to 0.5 ml/min per site (30 ml/hour per site). If well tolerated, the infusion rate can be increased to 2.0 ml/min per site (120 ml/hour per site) for subsequent infusions. Thereafter, the infusion rate can be increased further based on your tolerability.

Usage instructions

If you have any doubts about the use of this product, consult your doctor, pharmacist, or nurse.

If you use more Hizentra than you should

Inform your doctor as soon as possible if you think you have received too much Hizentra.

If you forgot to use Hizentra

Inform your doctor as soon as possible if you think you have missed a dose.

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

• In isolated cases, you may be allergic (hypersensitive) to the immunoglobulins and may experience allergic reactions such as a sudden drop in blood pressure or shock (e.g., you may feel dizzy or nauseous, feel dizziness when standing up, have cold hands and feet, an abnormal sensation of heart palpitations or chest pain, or have blurry vision).
• In isolated cases, you may experience pain and/or swelling of an arm or leg with warmth in the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or discomfort that worsens with deep breathing, unexplained rapid pulse, numbness or weakness on one side of the body, sudden confusion or difficulty speaking or understanding, which may be signs of a blood clot.
• In isolated cases, you may have a severe headache with nausea, vomiting, stiffness in the neck, fever, and sensitivity to light, which may be signs of ASMA (aseptic meningitis syndrome), which is a reversible, non-infectious, temporary inflammation of the membranes surrounding the brain and spinal cord.

• If you notice such signs during Hizentra infusion, stop the infusion and go to the nearest hospital immediately.

See also section 2 of this leaflet on the risk of allergic reactions, blood clots, and ASMA.

The adverse effects observed in controlled clinical trials are presented in decreasing order of frequency. The adverse effects observed post-marketing are of unknown frequency:

The following adverse effects arevery common(affect more than 1 in 10 patients):

• Headache
• Rash
• Reactions at the infusion site

The following adverse effects arecommon(affect between 1 and 10 patients in 100):

• Dizziness
• Migraine
• Increased blood pressure (hypertension)
• Diarrhea
• Abdominal pain
• General discomfort (nausea)
• Vomiting
• Itching (pruritus)
• Hives (urticaria)
• Musculoskeletal pain (musculoskeletal pain)
• Fever
• Joint pain (arthralgia)
• Weakness (fatigue), including general malaise
• Chest pain
• Symptoms similar to the flu
• Pain

The following adverse effects areuncommon(affect between 1 and 10 patients in 1,000):

• Hypersensitivity
• Involuntary movements in one or more parts of the body (tremors, including hyperactivity)
• Fast heart rate (tachycardia)
• Redness
• Muscle spasms
• Muscle weakness
• Chills, including low body temperature
• Abnormal laboratory test results that may indicate liver and kidney function abnormalities

In isolated cases, you may experience a ulcer at the infusion site or a burning sensation.

• You may reduce possible adverse effects by infusing Hizentra slowly.

These adverse effects may occur even if you have previously received human immunoglobulins and have tolerated them well.

See also section 2 "What you need to know before starting to use Hizentra", where you will find additional information on the factors that may increase the risk of experiencing adverse effects.

Reporting of adverse effects

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

By reporting adverse effects, you can contribute to providing more information on 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 packaging and on the vial label after EXP.
• You must use/dilute this medication as soon as possible after opening the vial.Do not use Hizentra if the vial is open or defective.
• Do not store above 25 °C.
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Do not throw away medications through drains or in the trash. Ask your pharmacist where to dispose of unused medications. This will help protect the environment.

Composition of Hizentra

• Theactive principleis human normal immunoglobulin. One milliliter contains 200 mg of human normal immunoglobulin, of which at least 98% is immunoglobulin of type G (IgG).

The approximate percentage of IgG subclasses is as follows:

IgG1 .................................. 69%

IgG2 .................................. 26%

IgG3 .................................. 3%

IgG4 .................................. 2%

This medicine contains traces of IgA (not more than 50 micrograms/ml).

• Theother components(excipients) are L-proline, polisorbate 80, and water for injection.

Appearance of Hizentra and contents of the package

Hizentra is a subcutaneous injectable solution (200 mg/ml). The color may vary from pale yellow to light brown.

Hizentra is available in vials of 5, 10, 20, or 50 ml.

Hizentra is also available in pre-filled syringes of 5, 10, 20, and 50 ml.

Package sizes

Packs of 1, 10, or 20 vials.

Hizentra is also available in packages of 1(for 5, 10, 20, 50 ml)or 10(for 5, 10, 20 ml)or 20(for 10, 20 ml)pre-filled syringes.

Please note that this package does not contain alcohol wipes, needles, or other accessories or equipment.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

D-35041 Marburg

Germany

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

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

----------------------------------------------------------------------------------------------------------------