HIZENTRA 200 mg /Ml Injectable Solution

Зміст інструкції

1. Hizentra 200 mg/ml solution for subcutaneous injection
   1. What is Hizentra and what is it used for
   2. What you need to know before you use Hizentra
   3. How to use Hizentra
   4. Possible side effects
   5. How to store Hizentra
   6. Contents of the pack and other information
2. Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe
   1. What Hizentra is and what it is used for
   2. What you need to know before you use Hizentra
   3. How to use Hizentra
   4. Possible side effects
   5. How to store Hizentra
   6. Package contents and other information

Hizentra 200 mg/ml solution for subcutaneous injection

Normal human immunoglobulin (SCIg = subcutaneous immunoglobulin)

Read this leaflet carefully before you start using this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or healthcare professional.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your healthcare professional. See section 4.

Contents of this leaflet

• 1. What Hizentra is and what it is used for
• 2. What you need to know before you use 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 is Hizentra and what is it used for

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

How Hizentra works
Hizentra contains immunoglobulins prepared from the blood of healthy people. Immunoglobulins are
produced by the human body's immune system. They help your body fight
infections caused by bacteria and viruses or maintain the balance of your immune system (an action
defined as immunomodulation). The medicine works exactly like the immunoglobulins present
naturally in the body.

What is Hizentra used for

Replacement therapy
Hizentra is used to increase pathologically low levels of immunoglobulins in the blood
bringing them back to normal values (replacement therapy). The medicine is used in adults and children
(0 – 18 years) in the following situations:

• 1. Treatment of patients with reduced or absent ability from birth to produce immunoglobulins (primary immunodeficiencies), including conditions such as:
• low levels of immunoglobulins (hypogammaglobulinemia) or absence of immunoglobulins (agammaglobulinemia) in the blood
• combination of low levels of immunoglobulins, frequent infections and inability to produce adequate amounts of antibodies after vaccinations (common variable immunodeficiency)
• combination of low levels or absence of immunoglobulins and absence or malfunction of immune cells (severe combined immunodeficiency)
• deficiency of certain subclasses of immunoglobulin G that causes recurrent infections.

• 2. Treatment of patients with low or dysfunctional levels of immunoglobulins 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 form of autoimmune disease. CIDP is characterized by chronic inflammation of the peripheral nerves
causing muscle weakness and/or numbness primarily in the legs and
arms.
It is believed that an attack on the body's defenses underlies this inflammation, and that the
immunoglobulins present in Hizentra help protect the nerves from attack (immunomodulatory therapy).

2. What you need to know before you use Hizentra

DO NOTinfuse Hizentra:
► if you are allergic to human immunoglobulins, polysorbate 80 or L-proline.
Before treatment, inform your doctor or healthcare professionals if you have previously experienced
intolerance to any of these components.
► if you suffer from hyperprolinemia (a genetic disorder that causes high levels of the amino acid
proline in the blood).
► into a blood vessel.

Warnings and precautions
➔ Consult your doctor or healthcare professional 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 in the past and
tolerated them well. This is particularly possible if you do not have enough immunoglobulin A (IgA) in
your blood (IgA deficiency).
Inform your doctor or healthcare professionals before treatment if you have an IgA deficiency.
Hizentra contains residual amounts of IgA that can cause an allergic reaction.
In these rare cases, allergic reactions may occur, such as a sudden drop in blood pressure or shock (see
also section 4 “Possible side effects”).
If you notice these reactions during the infusion of Hizentra, stop the infusion and contact your
doctor or go immediately to the nearest hospital.
Inform your doctor if you have previously had heart or blood vessel diseases or blood clots, if your
blood is thick or if you have been immobile for a long time. These factors can increase the
risk of blood clot formation after using Hizentra. Also inform your doctor about the medicines you are
currently taking, as some medicines, for example, those containing the estrogen hormone (e.g., birth
control pills), can increase the risk of blood clot formation. Seek immediate medical attention if, after
receiving Hizentra, you experience signs and symptoms such as shortness of breath, chest pain, pain and
swelling of a limb, weakness or numbness on one side of the body.
Consult your doctor if you experience the following signs and symptoms: severe headache, stiff neck,
drowsiness, fever, photophobia, nausea and vomiting after receiving Hizentra.
The doctor will decide whether further tests are necessary and whether therapy with Hizentra should be
continued.

Healthcare professionals will avoid potential complications by ensuring that:
► You are not sensitive to normal human immunoglobulins.
The medicine must be initially infused slowly. The recommended infusion rate, indicated in section 3
“How to use Hizentra”, must be strictly followed.
► You are closely monitored for the appearance of any symptoms throughout the duration of the infusion,
especially if:

• You are receiving normal human immunoglobulin for the first time
• You have previously been treated with another medicine
• a long interval of time (more than eight weeks) has passed since the previous infusion. In these cases, you will need to be closely monitored throughout the first infusion and for at least one hour after the infusion. If the above points do not apply to you, monitoring for at least 20 minutes after administration is recommended.

Other medicines and Hizentra
Inform your doctor or healthcare professional if you are taking, have recently taken or may take
any other medicines.
You must not mix other medicines with Hizentra.
Before vaccination, inform the doctor performing the vaccination about the treatment with
Hizentra.
Hizentra may impair the effect of some vaccines containing live viruses, such as measles,
rubella, mumps and varicella. Therefore, after taking this medicine, you may need to
delay vaccination with live attenuated vaccines for a period of up to 3 months. In the case of
measles, the reduction in vaccine efficacy may persist for up to 1 year.

Pregnancy, breastfeeding and fertility
Inform your doctor or healthcare professionals if you are pregnant, planning a pregnancy or
breastfeeding. The doctor will decide whether Hizentra can be administered during pregnancy or
breastfeeding.
Clinical studies with Hizentra in pregnant women have not been conducted. However, medicines
containing immunoglobulins have been used for years in pregnant or breastfeeding women without any
adverse effects on the course of pregnancy or the newborn being observed.
If you are breastfeeding and receive Hizentra, the immunoglobulins contained in the medicine may also be
detected in breast milk. Therefore, the newborn may be protected against some infections.

Driving and operating machinery
During treatment with Hizentra, patients may experience sensations such as dizziness or
nausea, which can affect the ability to drive vehicles and operate machinery. If this happens, do not
drive or operate machinery until these effects have disappeared

Hizentra contains proline
You should avoid Hizentra if you suffer from hyperprolinemia (see also section 2 “What you need to know
before you use Hizentra”). Inform your doctor before treatment.

Other important information about Hizentra
Blood tests
After the administration of Hizentra, the results of certain blood tests (serological tests) may be
altered for a certain period of time.
Before any blood test, inform your doctor about the treatment with Hizentra.
Information on the components of Hizentra
Hizentra is produced from human blood plasma (plasma is the liquid part of blood). For medicines
derived from human blood or plasma, certain safety measures must be adopted to prevent infections from
being transmitted to patients. The safety measures include:

• careful selection of plasma and blood donors, to exclude subjects who may be carriers of infections, and
• analysis of each donation and plasma pooled from multiple donors, to detect any signs of viruses/infections.

In the processing phases of blood and plasma, manufacturers of the medicine also include steps to
inactivate or remove any viruses. Despite these measures, the risk of transmitting infections can never be
completely excluded when administering medicines derived from human blood or plasma. This also applies
to unknown or new viruses or other types of infection.
The measures taken are considered effective against enveloped viruses, such as the human
immunodeficiency virus (HIV, the AIDS virus), the hepatitis B virus and the hepatitis C virus (liver
inflammation), and against non-enveloped viruses such as hepatitis A and parvovirus B19.
Whenever you take a dose of Hizentra, we strongly recommend that you record the name and batch
number of the medicine, to keep track of the batches used (see section 3 “How to use Hizentra”).

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

3. How to use Hizentra

Use this medicine following the doctor's instructions exactly. If you have any doubts, consult your
doctor.

Dosage
The doctor will calculate the correct dose for you, taking into account your body weight and your response to
treatment.
The dose or the administration interval must not be changed without consulting your doctor.
If you think you should receive Hizentra more or less frequently, please talk to your doctor.
If you think you have missed a dose, talk to your doctor as soon as possible.

Replacement therapy
The doctor will determine if you need a loading dose (for adults and children) of at least 1 -
2.5 ml/kg of body weight, divided over several days. After this dose, maintenance doses can be administered at repeated intervals, with a frequency from daily to once every two
weeks, to achieve a cumulative monthly dose of approximately 2 - 4 ml/kg of body weight.
The healthcare professional can calibrate the dose based on the response to treatment.

Immunomodulatory therapy
The doctor will start therapy with Hizentra 1 week after the last intravenous immunoglobulin infusion, administering subcutaneously, a weekly dose of 1.0 to 2.0
ml/kg of body weight. The doctor will determine your weekly dose of Hizentra. Weekly
maintenance doses can be divided into smaller doses and administered more frequently
during the week. For every two-week administration, the doctor will double the weekly dose
of Hizentra. The doctor may adjust the dose based on your response to treatment.

Method and route of administration
Home treatment will be initiated by a healthcare professional, experienced in the treatment
of immunodeficiency/CIDP with SCIg and in guiding patients in home therapy.
You will receive instructions and training on:

• aseptic infusion techniques
• how to keep a treatment diary, and
• the measures to be taken in case of serious adverse reactions.

Infusion sites

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

Infusion rate
The doctor will determine the appropriate infusion technique and infusion rate for you, taking
into account your individual dosage, frequency of administration, and product tolerability.
Infusion with infusion device
The recommended initial infusion rate should not exceed 20 ml/h/site. If well tolerated, you can
gradually increase the infusion rate to 35 ml/h/site for the next two infusions.
Subsequently, the infusion rate can be further increased based on your
tolerability.
Manual push infusion
The recommended initial infusion rate is up to 0.5 ml/min/site (30 ml/hour/site). If well
tolerated, the infusion rate can be increased up to 2.0 ml/min/site (120 ml/hour/site) for
subsequent infusions. Subsequently, the infusion rate can be further increased
according to your tolerability.

Instructions for use

	comparable to the amount of Hizentra to be withdrawn. Then, insert the needle into the center of the vial stopper and, to avoid o foam formation, inject air into the upper space of the vial (not into the liquid). Finally, aspirate the desired volume c of Hizentra. When using multiple vials to obtain the desired dose, repeat this step. a
6	m Prepare the infusion line r Connect the infusion line or injection set to the syringe. Prime the infusion line to eliminate any remaining air.
7	a Prepare the infusion site(s) Choose the infusion site(s) – The number and position of the infusion sites depend on the volume of the total dose. Each infusion site must be at least 5 cm apart from others. It is possible to use an unlimited number of sites l simultaneously e d Clean the infusion site(s) using a skin disinfectant solution. Let each site dry before proceeding.
8	a n Insert the needle Pinch the skin between two fingers and insert the needle into the subcutaneous tissue. a Secure the needle to the skin – If necessary, use gauze and adhesive tape or a transparent dressing to hold the needle in i position. l a
9	t I Infuse Hizentra Start the infusion. If you are using an infusion pump, follow the manufacturer's instructions.
10	a i Record the infusion Record the following data in the treatment diary: z the date of administration, the batch number of the medicine, and n the volume infused, the infusion rate, the number and location of the infusion sites.
11	e Clean up After administration, dispose of unused product and all devices used for administration, in accordance with local regulations.

If you have any doubts about the use of the medicine, contact your doctor or healthcare professionals.

If you use more Hizentra than you should
If you think you have used too much Hizentra, contact your doctor as soon as possible.

If you forget to use Hizentra
If you think you have forgotten a dose, contact your doctor as soon as possible.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
►In rare cases, you may become allergic (hypersensitive) to the immunoglobulins and allergic reactions may occur, such as a sudden drop in blood pressure or shock (for example,
you may feel mental confusion, dizziness, weakness when standing up, cold hands
and feet, abnormal heartbeat or chest pain or have blurred vision).
► In rare cases, you may experience pain and/or swelling in an arm or leg, with a feeling
of warmth in the affected area, a change in the color of the skin of the arm or leg,
unexplained shortness of breath, pain or discomfort in the chest, which worsens with deep breathing,
unexplainably rapid pulse, numbness or weakness on one side of the body,
sudden confusion, or difficulty speaking or understanding, all of which may be signs of
blood clot formation.
► In rare cases, you may experience a severe headache with nausea, vomiting, stiff neck, fever, and
sensitivity to light, which may be signs of AMS (aseptic meningitis syndrome), which is
a temporary, reversible, non-infectious inflammation of the membranes surrounding the
brain and spinal cord.
If you notice these signs during the infusion of Hizentra, stop the infusion and go
immediately to the nearest hospital.
allergic reactions, blood clots and AMS.
The side effects observed in controlled clinical trials are listed in decreasing order of frequency:
Side effects observed after marketing have
unknown frequency:
The following side effects are very common(occur in more than 1 in 10 patients):

• Headache
• Rash
• Infusion site reactions

The following side effects are common(occur in 1 to 10 patients in 100):

• Dizziness
• Migraine
• Increased blood pressure (hypertension)
• Diarrhea
• Abdominal pain
• Feeling unwell (nausea)
• Vomiting
• Itching
• Urticaria
• Muscle and bone related pain (musculoskeletal pain)
• Joint pain (arthralgia)
• Fever
• Fatigue, including general malaise
• Chest pain
• Flu-like symptoms
• Pain

The following side effects are uncommon(occur in 1 to 10 patients in 1,000):

• Hypersensitivity
• Involuntary movements in one or more parts of the body (tremor, including psychomotor hyperactivity).
• Fast heartbeat (tachycardia)
• Flushing
• Muscle spasms
• Muscle weakness
• Chills, including low body temperature
• Abnormal blood test results that may indicate decreased liver and kidney function

In rare cases, ulcers or a burning sensation may occur at the infusion site.
A slow infusion of Hizentra may reduce possible side effects.
These side effects may occur even if you have received human immunoglobulins in the
past and tolerated them well.
See also section 2 “What you need to know before using Hizentra” for further details on
circumstances that increase the risk of side effects.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or healthcare professional. You can also report side effects directly through
the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Hizentra

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the outer carton and on the vial label, after Scad.
• Since the solution does not contain preservatives, it must be used/infused, as soon as possible, after opening the vial.
• Do not store at a temperature above 25°C.
• Do not freeze.
• Keep the vial in the outer packaging, to protect the medicine from light.
• Do not dispose of any medicine in wastewater or household waste. Ask your healthcare professional how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Hizentra contains

• The active substanceis normal human immunoglobulin. 1 ml contains 200 mg of normal human immunoglobulins, of which at least 98% is represented by immunoglobulin type G (IgG). The approximate percentage of IgG subclasses is as follows: IgG1 69%

IgG2 26%
IgG3 3%
IgG4 2%
The medicine contains traces of IgA (not more than 50 micrograms/ml).

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

Description of the appearance of Hizentra and contents of the pack
Hizentra is a solution for subcutaneous injection (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 and 20 ml.

Packs
Packs of 1, 10 or 20 vials
Hizentra is also available in packs of 1, 10 or 20 pre-filled syringes.
Please note that alcohol wipes, needles and other devices or equipment are not
included in the pack.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
D35041 Marburg
Germany
For further information on this medicine, contact the local representative of the marketing authorisation
holder:

België/Belgique/Belgien
CSL Behring NV
Tél/Tel: +32 15 28 89 20

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20

България
МагнаФарм България ЕАД
Тел: +359 2 810 3949

Magyarország
CSL Behring Kft.
Tel: +36 1 213 4290

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Eesti
CentralPharma Communications OÜ
Tel: +3726015540

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Polska
CSL Behring Sp. z o.o.
Tel: +48 22 213 22 65

España
CSL Behring S.A.
Tel: +34 933 67 1870

Portugal
CSL Behring Lda
Tel: +351 21 782 62 30

France
CSL Behring SA
Tél: + 33 1 53 58 54 00

România
Prisum Healthcare S.R.L.
Tel: +40 21 322 01 71

Hrvatska
Marti Farm d.o.o
Tel: +385 1 5588297

Slovenija
EMMES BIOPHARMA GLOBAL s.r.o. -
podružnica v Sloveniji
Tel: +386 41 42 0002

Ireland
CSL Behring GmbH
Tel: +49 69 305 17254

Slovenská republika
CSL Behring Slovakia s.r.o.
Tel: +421 911 653 862

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

United Kingdom (Northern Ireland)
CSL Behring GmbH
Tel: +49 69 305 17254

Latvija
CentralPharma Communications SIA
Tel: +371 6 7450497

Lietuva
CentralPharma Communications UAB
Tel: +370 5 243 0444
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu.
----------------------------------------------------------------------------------------------------------------------------

Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe

Normal human immunoglobulin (SCIg = subcutaneous immunoglobulin)

Read this leaflet carefully before you start to use this medicine as it contains important
information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or healthcare professional.
• This medicine has been prescribed for you only. Do not pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If you get any side effects, even those not listed in this leaflet, tell your healthcare professional. See section 4.

Contents of this leaflet

• 1. What Hizentra is and what it is used for
• 2. What you need to know before you use 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 the class of medicines known as normal human immunoglobulins. Immunoglobulins are also called antibodies and are blood proteins that help the body fight infections.

How Hizentra works
Hizentra contains immunoglobulins prepared from the blood of healthy people. Immunoglobulins are produced by the human body's immune system. They help your body fight infections caused by bacteria and viruses or maintain the balance of your immune system (an action defined as immunomodulation). The medicine works exactly like the immunoglobulins naturally present in the body.

What Hizentra is used for

Replacement therapy
Hizentra is used to increase pathologically low levels of immunoglobulins in the blood, bringing them back to normal values (replacement therapy). The medicine is used in adults and children (0 – 18 years) in the following situations:

• 1. Treatment of patients with reduced or inability from birth to produce immunoglobulins (primary immunodeficiencies), including conditions such as:
• low levels of immunoglobulins (hypogammaglobulinemia) or absence of immunoglobulins (agammaglobulinemia) in the blood
• combination of low levels of immunoglobulins, frequent infections and inability to produce adequate amounts of antibodies after vaccinations (common variable immunodeficiency)
• combination of low or absent levels of immunoglobulins and absence or malfunction of immune cells (severe combined immunodeficiency)
• deficiency of certain subclasses of immunoglobulin G that causes recurrent infections.

• 2. Treatment of patients with low or dysfunctional levels of immunoglobulins 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 form of autoimmune disease. CIDP is characterized by chronic inflammation of the peripheral nerves that causes muscle weakness and/or numbness primarily in the legs and arms.
It is believed that an attack on the body's defenses underlies this inflammation, and that the immunoglobulins present in Hizentra help protect the nerves from attack (immunomodulatory therapy).

2. What you need to know before you use Hizentra

DO NOT infuseHizentra:
► if you are allergic to human immunoglobulins, polysorbate 80 or L-proline.
➔ Before treatment, inform your doctor or healthcare professionals if you have previously experienced
intolerance to any of these components.
► if you suffer from hyperprolinemia (a genetic disorder that causes high levels of the amino acid
proline in the blood).
► into a blood vessel.

Warnings and precautions
➔ Consult your doctor or healthcare professional 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 in the past and
tolerated them well. This is particularly possible if you do not have enough
immunoglobulin A (IgA) in your blood (IgA deficiency).
Inform your doctor or healthcare professionals before treatment if you have a deficiency of
immunoglobulin A (IgA). Hizentra contains residual amounts of IgA which can
cause an allergic reaction.
In these rare cases, allergic reactions may occur, such as a sudden drop in blood
pressure or shock (see also section 4 “Possible side effects”).
➔ If you notice these reactions during the infusion of Hizentra, stop the infusion and contact your
doctor or go immediately to the nearest hospital.
➔ Inform your doctor if you have previously had heart or blood vessel diseases or blood
clots, if your blood is thick or if you have been immobile for a long time. These factors can increase the
risk of blood clot formation after using Hizentra. Also inform your doctor
about the medicines you are currently taking, as some medicines, for example those containing
the estrogen hormone (e.g. contraceptive pills) can increase the risk of
blood clot formation. Seek immediate medical attention if you experience signs and
symptoms such as shortness of breath, chest pain, pain and swelling of a limb, weakness or
numbness on one side of the body after receiving Hizentra.
➔ Consult your doctor if the following signs and symptoms appear: severe headache, stiff
neck, drowsiness, fever, photophobia, nausea and vomiting, after receiving Hizentra. The
doctor will decide whether further tests are necessary and whether therapy with Hizentra should be
continued.

Healthcare professionals will avoid potential complications by ensuring that:
► You are not sensitive to normal human immunoglobulins.
The medicine should initially be injected slowly. The recommended infusion rate,
indicated in section 3 “How to use Hizentra”, must be strictly adhered to.
► You are carefully monitored for the appearance of any symptoms
throughout the duration of the infusion, especially if:

• You are receiving normal human immunoglobulin for the first time
• You have previously been treated with another medicine
• a long interval of time (more than eight weeks) has passed since the previous infusion. In these cases, you will need to be kept under close observation throughout the first infusion and for at least one hour after the infusion. If the above points do not apply to you, monitoring for at least 20 minutes after administration is recommended.

Other medicines and Hizentra
Inform your doctor or healthcare professional if you are taking, have recently taken or may take
any other medicines.
You must not mix other medicines with Hizentra.
Before vaccination, inform the doctor performing the vaccination about the treatment with
Hizentra.
Hizentra may impair the effect of some vaccines containing live viruses, such as measles,
mumps, rubella and varicella. Therefore, after taking this medicine, you may have to
delay vaccination with live attenuated vaccines for a period of up to three months. In the case of
measles, the reduction in vaccine efficacy may persist for up to 1 year.

Pregnancy, breastfeeding and fertility
Inform your doctor or healthcare professionals if you are pregnant, planning a
pregnancy or breastfeeding. The doctor will decide whether Hizentra can be administered to you
during pregnancy or breastfeeding.
Clinical studies with Hizentra in pregnant women have not been conducted. However, medicines
containing immunoglobulins have been used for years in pregnant women or breastfeeding mothers without
any adverse effects on the course of pregnancy or the newborn being observed.
If you are breastfeeding and receive Hizentra, the immunoglobulins contained in the medicine may be
found in breast milk. Therefore, the infant may be protected from some infections.

Driving and operating machinery
Patients may experience sensations such as dizziness or nausea during treatment with
Hizentra, which may affect the ability to drive vehicles and operate machinery. If this happens, do not
drive or operate machinery until these effects have disappeared.

Hizentra contains proline
You must avoid Hizentra if you suffer from hyperprolinemia (see also section 2 “What you need to know
before you use Hizentra”). Inform your doctor before treatment.

Other important information about Hizentra
Blood tests
After the administration of Hizentra, the results of certain blood tests (serological tests)
may be altered for a certain period of time.
➔ Before any blood test, inform your doctor about the treatment with Hizentra.
Information about the components of Hizentra
Hizentra is produced from human blood plasma (plasma is the liquid part of blood). For
medicines derived from human blood or plasma, certain safety measures must be adopted,
to prevent infections from being transmitted to patients. The safety measures include:

• careful selection of plasma and blood donors, so as to exclude subjects who may be carriers of infections, and
• analysis of each donation and of pooled plasma from multiple donors to detect any signs of viruses/infections. In the processing of blood and plasma, manufacturers of the medicine also include steps to inactivate or remove any viruses. Despite these measures, the risk of transmission of infections cannot be completely excluded when medicines derived from human blood or plasma are administered. This applies even to unknown or new viruses or other types of infection.

The measures taken are considered effective against enveloped viruses, such as the human immunodeficiency
virus (HIV, the AIDS virus), the hepatitis B virus and the hepatitis C virus
(inflammation of the liver), and against non-enveloped viruses such as hepatitis A and parvovirus B19.
➔ Whenever you take a dose of Hizentra, we recommend that you record the name and
batch number of the medicine to keep track of the batches used (see section 3 "How
to use Hizentra”).

Hizentra contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per vial/syringe, i.e.
essentially “sodium-free”.

3. How to use Hizentra

Use this medicine following the instructions of your doctor exactly. If you have any doubts, consult your
doctor.

Dosage
The doctor will calculate the correct dose for you, taking into account your body weight and your response to
treatment.
The dose or the interval of administration must not be changed without consulting the doctor.
If you think you need to receive Hizentra more or less frequently, please talk to your doctor.
If you think you have missed a dose, talk to your doctor as soon as possible.

Replacement therapy
The doctor will determine if you need a loading dose (for adults and children) of at least 1 -
2.5 ml/kg of body weight, divided over several days. After this dose, maintenance doses can be administered at repeated intervals, with a frequency from daily to once every two
weeks, to achieve a cumulative monthly dose of approximately 2 - 4 ml/kg of body weight.
The healthcare professional may calibrate the dose based on the response to treatment.

Immunomodulatory therapy
The doctor will start therapy with Hizentra 1 week after the last intravenous immunoglobulin
infusion, administering subcutaneously a weekly dose of 1.0 to 2.0 ml/kg
of body weight. The doctor will determine your weekly dose of Hizentra. Weekly maintenance doses can be divided into smaller doses and administered more frequently during the
week. For administration every two weeks, the doctor will double the weekly dose of
Hizentra. The doctor may adjust the dose based on your response to treatment.

Method and route of administration
Home treatment will be initiated by a healthcare professional experienced in the treatment
of immunodeficiency/CIDP with SCIg and in guiding patients in home therapy.
You will receive instructions and training on:

• aseptic infusion techniques
• how to keep a treatment diary, and
• the measures to be taken in case of serious adverse effects.

Infusion sites

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

Infusion rate
The doctor will determine the appropriate infusion technique and rate for you, taking
into account your individual dosage, frequency of administration, and tolerability of the
product.
Infusion with infusion device
The recommended initial infusion rate should not exceed 20 ml/h/site. If well tolerated, you can
gradually increase the infusion rate to 35 ml/h/site for the next two infusions.
Subsequently, the infusion rate can be further increased based on your
tolerability.
Manual push infusion:
The recommended initial infusion rate is up to 0.5 ml/min/site (30 ml/hour/site). If well
tolerated, the infusion rate can be increased up to 2.0 ml/min/site (120 ml/hour/site) for
subsequent infusions. Subsequently, the infusion rate can be further increased
according to your tolerability.

Instructions for use

Follow the instructions below and use aseptic conditions to administer Hizentra
1	a t Clean the surface Thoroughly clean the table or other flat surface using a disinfectant wipe
2	I Assemble the devices Place Hizentra and other devices needed for infusion on a flat, clean surface
3	Wash and dry your hands thoroughly
4	a Check the pre-filled syringe packs i Visually check the Hizentra solution for the presence of z particles or discoloration, as well as the expiration date before administering Hizentra. Do not use solutions if they appear n cloudy or if they contain particles. Do not use solutions that have been frozen. Administer the solution at room temperature e or body temperature. Once the pre-filled syringe pack has been opened, use the solution immediately. Please dispose of the oxygen absorber pack (which is located under the syringe).

5Preparing Hizentra for infusion

The 5, 10 and 20 ml pre-filled syringes are supplied ready
for use. The 5 ml and 10 ml pre-filled syringes (a.1) are
fully assembled.

For the 20 ml pre-filled syringes (b.1), before use
screw the plunger rod (b.3) onto the cap of the pre-filled syringe with an internal thread (b.4).

All pre-filled syringes have a standard luer lock (a.2 and
b.2), which is a screw connection on the tip of the syringe that
allows a leak-proof seal.
If you are using a syringe pump, the Hizentra pre-filled syringes can be placed directly into the syringe pump if the syringe size meets the pump's requirements.

If the pre-filled syringe can be placed directly
into the pump, then go to step 6.
If the size of the Hizentra pre-filled syringe does not
match the pump's requirements, then the contents of the
pre-filled syringe can be transferred to another syringe of
specific size for the pump.

6Prepare the infusion line
Connect the infusion line or injection set to the syringe. Load the infusion line in
order to eliminate any remaining air.

7Prepare the infusion site(s)
Choose the infusion site(s) –The number and position of the infusion sites depend on the volume of the total dose. Each infusion site must be at least 5 cm apart from the others.
You can use an unlimited number of sites
simultaneously

Clean the infusion site(s)using a skin disinfectant
solution. Allow each injection site to dry before
proceeding.

8Insert the needle
Grasp the skin between two fingers and insert the needle into the
subcutaneous tissue.

	Secure the needle to the skin – If necessary, use gauze and adhesive tape or a transparent dressing to hold the needle o in place. c a
9	m Infuse Hizentra r Start the infusion. If you are using an infusion pump, follow the manufacturer's instructions.
10	a Record the infusion F Record the following data in the treatment diary: the date of administration, the batch number of the medicine, and l the volume infused, the infusion rate, the number and position of the infusion sites.
11	e Clean up d After administration, dispose of unused product and all used administration devices including the oxygen absorber pack in accordance with local regulations.

If you have any doubts about the use of the medicine, contact your doctor or healthcare professionals.

If you use more Hizentra than you should
If you think you have used too much Hizentra, contact your doctor as soon as possible.

If you forget to use Hizentra
If you think you have forgotten a dose, contact your doctor as soon as possible.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone will experience them.
► In isolated cases, you may be allergic (hypersensitive) to immunoglobulins and allergic reactions may occur, such as a sudden drop in blood pressure or shock (for example,
you may feel dizzy, lightheaded, weak when standing up, cold in your hands and feet, irregular heartbeat or chest pain, or have blurred vision).
► In isolated cases, you may experience pain and/or swelling in an arm or leg with a sensation of
warmth in the affected area, a change in the color of the skin of the arm or leg,
unexplained shortness of breath, chest pain or discomfort that worsens with
deep breathing, inexplicably rapid pulse, numbness or weakness on one side of the
body, sudden confusion, or difficulty speaking or understanding may be signs of
a blood clot.
► In isolated cases, you may experience a severe headache with nausea, vomiting, stiff neck, fever, and sensitivity
to light, which may be signs of AMS (aseptic meningitis syndrome): a temporary reversible non-infectious inflammation of the membranes surrounding the brain and spinal
cord.
If you notice such signs during the infusion of Hizentra, stop the infusion and go to
the nearest hospital immediately.
allergic reactions, blood clots and AMS.
The side effects observed in controlled clinical trials are listed in decreasing order of frequency. Side effects observed after marketing have
unknown frequency:
The following side effects are very common(occur in more than 1 in 10 patients):

• Headache
• Rash
• Reactions at the infusion site

The following side effects are common(occur in 1 to 10 patients in 100):

• Dizziness
• Migraine
• Increased blood pressure (hypertension)
• Diarrhea
• Abdominal pain
• Feeling unwell (nausea)
• Vomiting
• Itching
• Hives
• Muscle and bone related pain (musculoskeletal pain)
• Joint pain (arthralgia)
• Fever
• Fatigue, including general malaise
• Chest pain
• Flu-like symptoms
• Pain

The following side effects are uncommon(occur in 1 - 10 patients per 1,000):

• Hypersensitivity
• Involuntary movements in one or more parts of the body (tremor, including psychomotor hyperactivity).
• Fast heartbeat (tachycardia)
• Flushing
• Muscle spasms
• Muscle weakness
• Chills, including low body temperature
• Abnormal blood test results indicating decreased liver and kidney function

In isolated cases, ulcers may occur at the infusion site or a burning sensation.
Possible side effects can be reduced by infusing Hizentra slowly.
These side effects may occur even if you have received human immunoglobulins in the
past and tolerated them well.
See also section 2 “What you need to know before using Hizentra” for further details on
circumstances that increase the risk of side effects.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your
doctor or healthcare professional. You can also report side effects directly through
the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-
avverse .
By reporting side effects you can help provide more information on the safety of
this medicine.

5. How to store Hizentra

• Keep this medicine out of the sight and reach of children.
• Do not use this medicine after the expiry date which is stated on the carton and on the label of the pre-filled syringe after Expiry.
• Since the solution does not contain preservatives, you must use/infuse it as soon as possible after opening the package with the pre-filled syringe.
• Do not store at a temperature above 25°C.
• Do not freeze.
• Keep the package with the pre-filled syringe in the outer packaging to protect the medicine from light.
• Do not dispose of any medicine in wastewater or household waste. Ask your healthcare provider how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Hizentra contains

• The active substanceis normal human immunoglobulin. One ml contains 200 mg of normal human immunoglobulins, of which at least 98% is represented by immunoglobulins of type G (IgG). The approximate percentage of IgG subclasses is as follows: IgG1 69% IgG2 26% IgG3 3% IgG4 2% The medicine contains traces of IgA (no more than 50 micrograms/ml).
• The other ingredients(excipients )are L-proline, polysorbate 80 and water for injections.

Description of the appearance of Hizentra and package contents
Hizentra is a solution for subcutaneous injection (200 mg/ml). The colour may vary from pale yellow
to light brown.
Hizentra is available in pre-filled syringes of 5, 10 or 20 ml. Each pre-filled syringe is
packaged in a blister containing an oxygen absorber pack to protect against
discoloration. Please dispose of the oxygen absorber pack.
Hizentra is also available in vials of 5, 10, 20 or 50 ml.

Pack sizes
Packs of 1, 10 or 20 pre-filled syringes.
Hizentra is also available in packs of 1, 10 or 20 vials.
Please note that alcohol swabs, needles and other devices or equipment are not
included in the pack.
Not all pack sizes may be marketed.

Marketing authorisation holder and manufacturer
CSL Behring GmbH
Emil-von-Behring-Strasse 76
D35041 Marburg
Germany
For further information on this medicine, contact the local representative of the marketing
authorisation holder:

België/Belgique/Belgien
CSL Behring NV
Tél/Tel: +32 15 28 89 20

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20

България
МагнаФарм България ЕАД
Тел: +359 2 810 3949

Magyarország
CSL Behring Kft.
Tel: +36 1 213 4290

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Eesti
CentralPharma Communications OÜ
Tel: +3726015540

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Polska
CSL Behring Sp. z o.o.
Tel: +48 22 213 22 65

España
CSL Behring S.A.
Tel: +34 933 67 1870

Portugal
CSL Behring Lda
Tel: +351 21 782 62 30

France
CSL Behring SA
Tél: + 33 1 53 58 54 00

România
Prisum Healthcare S.R.L.
Tel: +40 21 322 01 71

Hrvatska
Marti Farm d.o.o
Tel: +385 1 5588297

Slovenija
EMMES BIOPHARMA GLOBAL s.r.o. -
podružnica v Sloveniji Tel: +386 41 42 0002

Ireland
CSL Behring GmbH
Tel: +49 69 305 17254

Slovenská republika
CSL Behring Slovakia s.r.o.
Tel: +421 911 653 862

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

United Kingdom (Northern Ireland)
CSL Behring GmbH
Tel: +49 69 305 17254

Latvija
CentralPharma Communications SIA
Tel: +371 6 7450497

Lietuva
CentralPharma Communications UAB
Tel: +370 5 243 0444
More detailed information on this medicine is available on the website of the European Medicines
Agency: http://www.ema.europa.eu.
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