Hizentra 200 mg/ml solution for subcutaneous injection

What Hizentra is

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

How Hizentra works

Hizentra contains immunoglobulins that have been prepared from the blood of healthy people. The medicine works in exactly the same way as the immunoglobulins naturally present in your blood.

What Hizentra is used for

Hizentra is used to raise abnormally low immunoglobulin levels in your blood to normal levels (replacement therapy). The medicine is used in two different situations:

1. Treatment of adults and children who are born with a reduced ability or inability to produce immunoglobulins (primary immunodeficiencies). This includes conditions such as:

• low immunoglobulin levels (hypogammaglobulinaemia) or absence of immunoglobulins (agammaglobulinaemia) in the blood
• combination of low immunoglobulin levels, frequent infections and inability to produce adequate amounts of antibodies after vaccination (common variable immunodeficiency)
• combination of low level or absence of immunoglobulins and absence or non-functional immune cells (severe combined immunodeficiency)
• lack of certain immunoglobulin G subclasses causing recurrent infections.

2. Treatment of adults and children with certain kinds of blood cancer (such as myeloma or chronic lymphocytic leukaemia) which lead to severely low immunoglobulin levels in the blood and cause recurrent infections.

Do NOT inject Hizentra:

if you are allergic hypersensitive to human immunoglobulins, polysorbate 80 or L-proline. Tell your doctor or healthcare professional prior to treatment if you have experienced an intolerance against one of these components earlier. if you suffer from hyperprolinaemia a genetic disorder causing high levels of the amino acid proline in the blood. into a blood vessel.

Take special care with Hizentra

You may be allergic (hypersensitive) to immunoglobulins without knowing it. However, true allergic reactions are rare. They may occur even if you received human immunoglobulins previously and tolerated them well. It may happen particularly if you do not have enough of the immunoglobulin type A (IgA) in your blood (IgA deficiency). In these rare cases allergic reactions such as a sudden fall in blood pressure or shock may occur (e.g. you may feel light-headed, dizzy, faint on standing, cold in the hands and feet, sense an abnormal heart beat or chest pain, or have blurred vision). - If you notice such signs during the infusion of Hizentra, tell your doctor immediately. He or she will decide whether to slow down the infusion rate or whether to stop the infusion completely.

Your healthcare professional will avoid potential complications by ensuring:
- that you are not sensitive to human normal immunoglobulin.
The medicine must be infused slowly at first. The recommended infusion rate given under section 3 ?How to use Hizentra? must be closely followed.
- that you are carefully monitored for any symptoms throughout the infusion period, especially if:

• you receive human normal immunoglobulin for the first time
• you have switched from a different medicine
• there has been a long interval (more than eight weeks) since the previous infusion. In these cases, it is recommended that you are monitored during the first infusion and for an hour afterwards. If the points above do not apply for you it is recommended that you are observed for at least 20 minutes after administration.

Blood tests
After receiving Hizentra, the results of certain blood tests (serological tests) may be impaired for a certain time.
- Tell your doctor about your treatment with Hizentra prior to any blood test.

Information on what Hizentra is made of
Hizentra is made from human blood plasma (this is the liquid part of the blood). When medicines are made from human blood or plasma, certain measures are put in place to prevent infections being passed on to patients. These include:

• careful selection of blood and plasma donors to make sure those at risk of carrying infections are excluded, and
• the testing of each donation and pools of plasma for signs of virus/infections. Manufacturers of these medicines also include steps in the processing of the blood or plasma that can inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are administered, the possibility of passing on infection cannot be totally excluded. This also applies to any unknown or emerging viruses or other types of infections.

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

- It is recommended that every time you take Hizentra the following data are recorded in your treatment diary:

• the date of administration,
• the batch number of the medicine, and
• the injected volume, flow rate, the number and location of injection sites.

Taking other medicines

Tell your doctor or healthcare professional prior to treatment if you are currently taking any other medicines or if you have recently taken any other medicines. This also includes non-prescription medicines.

You must not mix other medicines with Hizentra.

Vaccinations
Hizentra may impair the effect of some live virus vaccines such as measles, rubella, mumps and chicken pox. Therefore, after receiving these medicines you may have to wait up to 3 months before receiving your live-attenuated vaccine. In the case of measles vaccinations the impairment may persist for up to 1 year.

Therefore your vaccinating doctor should check the efficacy of the measles vaccination. - Tell your vaccinating doctor prior to a vaccination about your treatment with Hizentra.

Pregnancy and breast-feeding

Tell your doctor or healthcare professional if you are pregnant, plan to become pregnant or are breast-feeding. Your doctor will decide whether you can receive Hizentra during your pregnancy or while you are breast-feeding.

No clinical studies have been performed with Hizentra in pregnant women. However, medicines that contain immunoglobulins have been used in pregnant or breast-feeding women for years, and no harmful effects on the course of pregnancy or on the baby have been observed.

If you are breast-feeding and receive Hizentra, the immunoglobulins of the medicine can also be found in the breast milk. Therefore, your baby may be protected from certain infections.

Driving and using machines

No effects of Hizentra on the ability to drive and use machines are expected.

Important information about some of the ingredients of Hizentra

Hizentra contains proline and you must not take it if you suffer from hyperprolinaemia (see also section 2 ?Before you use Hizentra?). Please tell your doctor prior to treatment.
Hizentra is essentially sodium free.
- Tell your doctor or healthcare professional prior to treatment if you have an immunoglobulin type A (IgA) deficiency. Hizentra contains residual amounts of IgA which might cause an allergic reaction.

Always use Hizentra exactly as your doctor has told you. Check with your doctor if you are not sure.

Your doctor will calculate the correct dose for you taking into account your weight and response to treatment.

Your doctor will determine whether 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. Following this, maintenance doses may be given,

usually weekly, to reach a cumulative monthly dose of about 2 to 4 ml/kg of body weight. Your healthcare professional may adjust the dose based on your response to the treatment.

Method of administration

In case of home treatment, this will be initiated by a healthcare professional experienced in the treatment of immunodeficiency and in the guidance of patients for home treatment.

• You will be instructed in:
• aseptic infusion techniques
• the keeping of a treatment diary, and
• measures to be taken in case of severe side effects.
• Hizentra is a ready-to-use solution (see section 5 ?How to store Hizentra? and section 6 ?What Hizentra looks like and contents of the pack?).
• Do not use solutions that are cloudy or contain particles.
• Do not use solutions that have been frozen.
• Administer solution which is at room or body temperature.
• Administer Hizentra under the skin only.
• You may inject Hizentra into sites such as abdomen, thigh, upper arm, and lateral hip. If large doses are given (> 25 ml), try to administer them at multiple sites.
• The recommended initial infusion rate is up to 15 ml/hour/site. If well-tolerated, the infusion rate can then gradually be increased to 25 ml/hour/site.
• You may use up to 4 injections sites simultaneously, provided that the maximum infusion rate for all sites combined does not exceed 50 ml/hour. Injection sites should be at least 5 cm apart.
• Once an injection vial has been opened, use the solution immediately.

If you have any further questions on the use of this medicine, please ask your doctor or healthcare professional.

If you use more Hizentra than you should

If you think you have had too much Hizentra, speak to your doctor as soon as possible.

If you use less Hizentra than you should

If you think you have missed a dose, speak to your doctor as soon as possible.

Like all medicines, Hizentra can have side effects, although not everybody gets them.

You may be allergic hypersensitive to immunoglobulins and allergic reactions such as a sudden fall in blood pressure or shock may occur e.g. you may feel light-headed, dizzy, faint on standing, cold in the hands and feet, sense an abnormal heart beat or chest pain, or have blurred vision. If you notice such signs during the infusion of Hizentra, tell your doctor immediately. Please see also section 2 of this leaflet about the risk of allergic reactions.

Possible side effects may be reduced or even avoided, by infusing Hizentra slowly.

The following side effects are very common (affects more than 1 infusion in 10):

• Reactions at the injection site

The following side effects are common (affects 1 to 10 infusions in 100):

• Headache

The following side effects are uncommon (affects 1 to 10 infusions in 1,000):

• Vomiting
• Itching (pruritus)
• Tiredness (fatigue)
• Pain

The following side effects are rare (affects 1 to 10 infusion s in 10,000):

• Common cold symptoms
• Hypersensitivity
• Dizziness
• Migraine
• Restlessness
• Sleepiness (somnolence)
• Fast heartbeat
• Bruising (haematoma and contusion)
• Hot flushes
• Cough
• Abdominal discomfort, distension, upper or lower abdominal pain
• Diarrhoea
• Feeling sick (nausea)
• Skin reactions such as irritation, redness, rash, blister
• Joint pain (arthralgia)
• Muscle weakness, spasms, aching muscles (myalgia)
• Pain in neck, back, chest, arms and/or legs
• Pain related to the musculature and bones (musculoskeletal pain)
• Blood in the urine (haematuria)
• Chills, feeling cold, low body temperature (hypothermia)
• Flu-like symptoms
• Generally feeling unwell (malaise)
• Fever
• Results of blood tests suggesting impaired liver and kidney function
• High blood pressure
• Weight loss

Side effects such as these may occur even when you have previously received human immunoglobulins and tolerated them well.

Tell your doctor or healthcare professional if any of the side effects get serious or if you notice any side effects not listed in this leaflet.

• Keep out of the reach and sight of children.
• Do not use after the expiry date which is stated on the outer carton and the vial label after EXP.
• Because the solution contains no preservative, Hizentra should be used/infused as soon as possible after opening the vial.
• Do not store above 25 °C.
• Do not freeze.
• Keep the vial in the outer carton in order to protect from light.
• Medicines should not be disposed of via wastewater or household waste. Ask your healthcare professional how to dispose of medicines no longer required. These measures will help to protect the environment.

What Hizentra contains

• The active substance is human normal immunoglobulin. One ml contains 200 mg of human plasma protein, of which at least 98% is immunoglobulin type G (IgG). The approximate percentage of IgG subclasses is as follows: IgG1 .............. 62-74% IgG2 .............. 22-34% IgG3 .............. 2-5% IgG4 .............. 1-3% This medicine contains trace amounts of IgA (not more than 0.050 mg/ml). Hizentra is essentially sodium free.
• The other ingredients are L-proline, polysorbate 80 and water for injections.

What Hizentra looks like and contents of the pack

Hizentra is a solution for subcutaneous injection (200 mg/ml). The colour can vary from pale-yellow to light-brown.
Hizentra is available in vials of 5, 10, 15 or 20 ml.

Pack sizes

Packs of 1, 10 or 20 vials
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76
35041 Marburg
Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

BelgiëBelgiqueBelgien CSL Behring NV Technologielaan 13 B-3001 Leuven TélTel 32 16 38 80 80 LuxembourgLuxemburg CSL Behring NV Technologielaan 13 B-3001 Leuven, BelgiqueBelgien TélTel 32 16 38 80 80

114, 1404, , 359 2 958 84 68 Magyarország Plazmed Kft. F u. 200 H-2193 Galgahévíz Tel. 36 28 59 10 00

eská republika IBP medica s.r.o. Pod Karlovem 81670 CZ 120 00 Praha 2 Tel 42 02 22 56 07 23 Malta AM Mangion Ltd. Mangion Buildings New Street in Valletta Road MT-LQA 6000 Luqa Tel 356 2397 6333

Danmark CSL Behring AB P.O.Box 712 S-182 17 Danderyd Tel 46 8 544 966 70 Nederland CSL Behring BV Claudius Prinsenlaan 128 NL-4818 CP Breda Tel 31 76 523 6045

Deutschland CSL Behring GmbH Philipp-Reis-Strasse 2 D-65795 Hattersheim Tel 49 69 30584437 Norge CSL Behring AB P.O.Box 712 S-182 17 Danderyd, Sverige Tlf 46 8 544 966 70

Eesti CSL Behring AB P.O.Box 712 S-182 17 Danderyd, Rootsi Tel 46 8 544 966 70 Österreich CSL Behring GmbH Altmannsdorfer Strasse 104 A-1121 Wien Tel 43 1 80101 2463

CSL Behring 5 GR-115 28 30 210 7255 660 Polska Imed Poland Sp. z o.o. Ul. Puawska 314 PL-02-812 Warszawa Tel. 48 22 663 43 10

España CSL Behring S.A. Av. Països Catalans, 34, 3aE-08950 Esplugues de Llobregat Barcelona Tel 34 933 67 1870 Portugal CSL Behring Lda Av. 5 de Outubro, 198 3 Esq. P-1050-064 Lisboa Tel 351 21 782 62 30

France CSL Behring SA 30 rue Cambronne F-75015 Paris Tél 33 1 53 58 54 00 România Nicofarma DCI SRL Strada Tepe Voda 79 Sector 2 Bucureti 021522 RO Tel 40 21 3272614

Slovenija MediSanus d.o.o. Vagajeva ulica 4 SI-1000 Ljubljana Tel 386 1 25 71 496 Ireland CSL Behring UK Ltd. Hayworth House, Market Place Haywards Heath, West Sussex RH16 1DB, UK Tel 44 1444 447400

Ísland CSL Behring AB P.O.Box 712 S-182 17 Danderyd, Svíjóð Sími 46 8 544 966 70 Slovenská republika TIMED, s.r.o. Trnavská cesta 112 SK-821 01 Bratislava Tel 421 2 4820 95 11

Italia CSL Behring S.p.A. Viale Del Ghisallo, 20 I-20151 Milano Tel 39 02 34964 200 SuomiFinland CSL Behring AB P.O.Box 712 S-182 17 Danderyd, RuotsiSverige PuhTel 46 8 544 966 70

. 4 CY-1522 357 22677038 Sverige CSL Behring AB P.O.Box 712 S-182 17 Danderyd Tel 46 8 544 966 70

Latvija CSL Behring AB P.O.Box 712 S-182 17 Danderyd, Zviedrija Tel 46 8 544 966 70 United Kingdom CSL Behring UK Ltd. Hayworth House, Market Place Haywards Heath, West Sussex RH16 1DB, UK Tel 44 01444 447400

Lietuva

CSL Behring AB
P.O.Box 712
S-182 17 Danderyd, ?vedija
Tel: +46 8 544 966 70

This leaflet was last approved in MM/YYYY

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