Hizentra 200 mg/ml solution for subcutaneous injection

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Hizentra 200 mg/ml solution for subcutaneous injection

normal human immunoglobulin (IgSC = I mmunog lobulin S ubc utaneous)

Read the entire leaflet carefully before you start using this medicine, because 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 must not be given to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

1. What Hizentra is and what it is used for
2. What you need to know before using Hizentra
3. How to use Hizentra
4. Possible side effects
5. How to store Hizentra
6. Contents of the pack and other information

1. What Hizentra is and what it is used for

What Hizentra is

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

How Hizentra works

Hizentra contains immunoglobulins obtained from the blood of healthy donors. Immunoglobulins are normally produced by the body's immune system. They help the body combat infections caused by bacteria and viruses or maintain balance in the immune system (known as immunomodulation). The medicine works in exactly the same way as the immunoglobulins naturally present in the blood.

What Hizentra is used for

Replacement therapy

Hizentra is used to raise abnormally low levels of immunoglobulin in the blood to normal levels (replacement therapy). The medicine is used in adults and children (0–18 years) in the following situations:

1. Treatment of patients born with a reduced or absent ability to produce immunoglobulins (primary immunodeficiencies). This includes conditions such as:

• Low levels of immunoglobulin (hypogammaglobulinemia) or absence of immunoglobulins in the blood (agammaglobulinemia)
• Combination of low immunoglobulin levels, frequent infections, and inability to produce adequate antibody levels after vaccination (common variable immunodeficiency)
• Combination of low or absent immunoglobulin levels and absence or dysfunction of immune cells (severe combined immunodeficiency)
• Deficiency of certain subclasses of immunoglobulin G causing recurrent infections.

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

Immunomodulatory therapy in CIDP patients

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

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

DO NOT infuse Hizentra:

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

Into 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 may occur even if you have previously received human immunoglobulins and tolerated them well. This is especially possible if you do not have sufficient levels of immunoglobulin type A (IgA) in your blood (IgA deficiency).

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

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

• If you notice symptoms of this type during Hizentra infusion, stop the infusion immediately and contact your doctor or go to the nearest hospital without delay.

• Inform your doctor if you have a history of heart or vascular disease, if you have had blood clots, have thick blood, or have been immobile for a period of time. These factors may increase your risk of developing a blood clot after receiving Hizentra. Also, tell your doctor which 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 signs and symptoms such as difficulty breathing, chest pain, pain and swelling in a limb, weakness, or numbness on one side of the body after taking Hizentra.

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

Your healthcare professional will prevent possible complications by ensuring that:

• You are not sensitive to normal human immunoglobulin.

The product should initially be injected slowly. The recommended infusion rate specified in section 3 “How to use Hizentra” must be strictly followed.

• You are closely monitored for any symptoms throughout the entire infusion period, especially if:

• It is the first time you are receiving normal human immunoglobulin.

• You have switched from treatment with another medicine.

• A prolonged period (more than eight weeks) has passed since your last infusion.

In these cases, you should be observed during the first infusion and for one hour afterward. If the above conditions do not apply to you, observation for at least 20 minutes after administration is recommended.

Interaction of Hizentra with other medicines

• Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.
• Hizentra must not be mixed with other medicines.
• Before getting vaccinated, inform your doctor about your treatment with Hizentra.

Hizentra may interfere with the effectiveness of certain live virus vaccines such as measles, mumps, rubella, and varicella vaccines. Therefore, you should wait at least 3 months after administration of Hizentra before receiving a live attenuated vaccine. In the case of the measles vaccine, this interference may last up to 1 year.

Pregnancy, breastfeeding, and fertility

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

Studies with Hizentra have not been conducted in pregnant women. However, medicines containing immunoglobulin have been used in pregnant and breastfeeding women for many years, and no harmful effects on pregnancy or the baby have been observed.

If you are breastfeeding and receive Hizentra, immunoglobulins from the medicine may also be present in breast milk. Therefore, your baby may be protected against certain infections.

Driving and use of machines

During treatment with Hizentra, patients may experience effects such as dizziness or nausea, which could affect their ability to drive or operate machinery. If this occurs, you should not drive or use machines until these effects have subsided.

Hizentra contains proline

Do not take this medicine 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, results of certain blood tests (serological tests) may be altered for some time.

• Before any blood test, inform your doctor about your treatment with Hizentra.

Information about the components of Hizentra

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

• meticulous selection of blood or plasma donors to ensure exclusion of potential carriers of infections, and
• testing of each donation and plasma pools for signs of viruses or infections.

Manufacturers of these medicines also include steps in the processing of blood or plasma that can inactivate or eliminate viruses. Despite these measures, when administering medicines prepared from human blood or plasma, the possibility of transmitting an infection cannot be completely ruled out. This also applies to any unknown or emerging virus or any other type of infection.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV, the AIDS virus), hepatitis B virus, and hepatitis C virus (liver inflammation), and also against 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 record the name and batch number of the product to maintain a record of the batches used (see section 3, “How to use Hizentra”).

Hizentra contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per vial/syringe; therefore, it is essentially “sodium-free”.

3. How to use Hizentra

Follow exactly the administration instructions for this medicine given by your doctor. Consult your doctor if you have any doubts.

Dosage

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

The dose or dosing interval must 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 missed a dose, speak with your doctor as soon as possible.

Replacement therapy

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

Immunomodulatory therapy

Your doctor will start Hizentra therapy one week after your last intravenous immunoglobulin infusion, administering it subcutaneously with a weekly dose of 1.0 to 2.0 ml/kg body weight. Your doctor will determine your weekly dose of Hizentra. Weekly maintenance doses may be divided into smaller doses and administered as frequently as needed during the week. For every-two-week schedules, your doctor will double the weekly dose of Hizentra. Your healthcare provider may adjust the dose based on your response to treatment.

Method and route of administration

For home treatment, initiation must be supervised by a healthcare professional experienced in treating immunodeficiency/PID with IgSC and in training patients for home therapy.

You will be instructed and trained in:

• aseptic infusion techniques,
• maintaining a treatment diary, and
• measures to take in case of serious adverse reactions.

Infusion site(s)

• Administer Hizentra only subcutaneously.
• You may infuse Hizentra at sites such as the abdomen, thigh, arm, and lateral hip. For high doses (> 50 ml), administer at multiple sites.
• You may use an unlimited number of injection sites simultaneously. Injection sites must be at least 5 cm apart from each other.
• If using device-assisted infusion technique (e.g., pump-assisted infusion), you may use more than one infusion device simultaneously.
• If using manual push technique with a syringe, only one infusion site may be used per syringe. If an additional syringe of Hizentra needs to be administered, a new sterile injection needle must be used and the infusion site changed.
• The volume of product infused at a given site may vary.

Infusion rate(s)

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 may be gradually increased to 35 ml/hour per site for the next two infusions. Thereafter, the infusion rate may be increased further according to 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 may be increased up to 2.0 ml/min per site (120 ml/hour per site) for subsequent infusions. Thereafter, the infusion rate may be further increased according to your tolerability.

Instructions for use

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 forget to use Hizentra

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

4. Possible side effects

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

• In rare cases, you may be allergic (hypersensitive) to immunoglobulins and allergic reactions may occur, such as a sudden drop in blood pressure or shock (e.g., you may feel confused or dizzy, feel lightheaded when standing up, have cold hands and feet, an abnormal sensation of heartbeat or chest pain, or blurred vision).

• In rare cases, you may experience pain and/or swelling in an arm or leg with warmth in the affected area, skin 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 could be signs of a blood clot.

• In rare cases, you may experience a severe headache with nausea, vomiting, neck stiffness, fever, and sensitivity to light, which could be signs of aseptic meningitis (AM), a temporary, non-infectious, reversible inflammation of the membranes surrounding the brain and spinal cord.

• If you notice any of these signs during Hizentra infusion, stop the infusion immediately and go to the nearest hospital without delay.

See also section 2 of this leaflet regarding the risk of allergic reactions, blood clots, and aseptic meningitis.

The side effects observed in controlled clinical trials are listed below in decreasing order of frequency. Side effects observed after marketing have unknown frequency:

The following side effects are very common (affect more than 1 in 10 patients):

• Headache
• Rash
• Reactions at the infusion site

The following side effects are common (affect between 1 and 10 out of 100 patients):

• Dizziness
• Migraine
• Increased blood pressure (hypertension)
• Diarrhea
• Abdominal pain
• General malaise (nausea)
• Vomiting
• Itching (pruritus)
• Hives (urticaria)
• Pain related to muscles and bones (musculoskeletal pain)
• Fever
• Joint pain (arthralgia)
• Tiredness (fatigue), including malaise (general discomfort)
• Chest pain
• Flu-like symptoms
• Pain

The following side effects are uncommon (affect between 1 and 10 out of 1,000 patients):

• Hypersensitivity
• Involuntary restlessness movements in one or more parts of the body (tremors, including psychomotor hyperactivity)
• Rapid heartbeat (tachycardia)
• Redness
• Muscle spasms
• Muscle weakness
• Chills, including low body temperature
• Abnormal blood test results that may indicate impaired liver or kidney function

In rare cases, an ulcer at the infusion site or a burning sensation may occur.

• You can reduce possible side effects by infusing Hizentra slowly.

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

See also section 2, "What you need to know before using Hizentra," for additional information on factors that may increase the risk of side effects.

Reporting of side effects

If you experience any type of side effect, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V.

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

5. Storage of Hizentra

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date stated on the container and on the label of the vial following EXP.
• This medicine should be used/infused as soon as possible after opening the vial. Do not use Hizentra if the vial is open or damaged.
• Do not store above 25 °C.
• Do not freeze.
• Store the vial in the outer packaging to protect it from light.
• Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

Composition of Hizentra

• The active substance is human normal immunoglobulin. One ml contains 200 mg of human normal immunoglobulin, of which at least 98% is immunoglobulin of the G type (IgG).

The approximate percentage of IgG subclasses is as follows:

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

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

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

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

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

• The other components (excipients) are L-proline, polysorbate 80, and water for injections.

Appearance of Hizentra and contents of the pack

Hizentra is a subcutaneous injectable solution (200 mg/ml). The colour 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.

Pack sizes

Packs of 1, 10 or 20 vials.

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

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

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76

D-35041 Marburg

Germany

More information about this medicine is available upon request from the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet:

Detailed information on this medicine is available on the European Medicines Agency website: https://www.ema.euopa.eu/.