Zutectra 500 IU solution for injection in pre-filled syringe

What Zutectra is

Zutectra contains antibodies against the hepatitis B virus which are the body's own defensive substances to protect you from hepatitis B. Hepatitis B is an inflammation of the liver caused by the hepatitis B virus.

What Zutectra is used for

Zutectra is used to prevent re-infection of hepatitis B in adults who have had a liver transplant at least 6 months ago because they had liver failure caused by hepatitis B.

Please read this section carefully. The information given should be taken into consideration by you and your doctor before you receive Zutectra.

Zutectrashould not be used

• if you are allergic (hypersensitive) to human immunoglobulin or any of the other ingredients of Zutectra (see list of ingredients in Section 6). An allergic reaction may include sudden wheeziness, difficulty in breathing, fast pulse, swelling of the eyelids, face, lips, throat or tongue, rash or itching.

Please tell your doctor or healthcare professional prior to treatment about any medicine or food which, previously, you have not tolerated well.

Take special care with Zutectra

Zutectra is for subcutaneous injection under the skin only. Injection into a vein or a blood vessel may result in allergic shock.

Please tell your doctor or healthcare professional prior to treatment

• if you have been told that you have antibodies against immunoglobulins of the type IgA in your blood. This is very rare and may result in allergic reactions.

You may be allergic (hypersensitive) to immunoglobulins (antibodies) without knowing it, even if you have tolerated previous treatments with human immunoglobulins. Particularly if you do not have enough immunoglobulins of the type IgA in your blood, allergic reactions such as a sudden fall in blood pressure or shock may occur.

You will be carefully observed during and shortly after the 1stinjection with Zutectra to make sure that you do not suffer from a reaction. If you have an allergic reaction to Zutectra, the injection will be stopped immediately. Please tell your doctor or healthcare professional immediately if you notice such reactions during your injection with Zutectra.

If you are HBs antigen positive you will not receive Zutectra since there is no benefit in administering this medicine to you. Your doctor will be able to explain this to you.

For your own safety you will be monitored for antibody levels regularly.

Information on the starting material of Zutectraand the possibility of transmission of infectious agents:

The starting material or what Zutectra is made from is 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), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped hepatitis A virus. The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19 virus.

Immunoglobulins like Zutectra have not been associated with hepatitis A or parvovirus B19 infections possibly because the antibodies against these infections, which are contained in the product, are protective.

It is strongly recommended that every time Zutectra is used (both at hospital or in a home treatment), the name and batch number of the medicine are recorded in order to maintain a record of the batches used.

Taking other medicines

Please tell your doctor or healthcare professional if you are taking or have recently taken any other medicines including medicines obtained without a prescription.

Vaccinations

Zutectra can reduce the effectiveness of some vaccines (measles, rubella, mumps, chicken pox) for a

period of up to 3 months.

You may have to wait at least 3 months after the last injection of Zutectra before you can have some vaccines.

Please tell your doctor about your treatment with Zutectra prior to any vaccination.

Blood tests

Zutectra might affect the results of certain blood tests (serological tests). Please tell your doctor about your treatment with Zutectra prior to any blood test.

Pregnancy and breast-feeding
Please tell your doctor or healthcare professional if you are pregnant or breast-feeding. Your doctor will decide whether you can receive Zutectra during pregnancy and breast-feeding.

Driving and using machines
Zutectra has no known effects on your ability to drive or use machines.

Zutectra is intended for subcutaneous (under the skin) injection. The contents of one syringe are intended for use once only. This medicine must not be injected into a blood vessel.

In most cases you will be given the injection by your doctor or nurse. However, if your antibody levels are sufficient and you have a fixed dosage regimen, you or your caregiver may be trained to carry out the injection at home (see below).

For the documentation of your injections of Zutectra it is strongly recommended to use the treatment diary. Your doctor will explain you how to use it.

The dose will depend on your condition and your body weight. Your doctor will tell you how much and how often you need to use Zutectra.

Adults

• patients with bodyweight less than 75 kg: 500 IU (1 ml) per week
• patients with bodyweight equal or more than 75 kg: 1000 IU (2 times 1 ml) per week

Up to 1000 IU per week can be given to get sufficient antibody levels.

Injecting by yourself or by caregiver

You can inject Zutectra yourself without the help of your doctor, if they have trained you to do this. If you are administering Zutectrayourself, please read instructions in the section ?HOW TO INJECT ZUTECTRA BY YOURSELF OR BY CAREGIVER? carefully.

If you use more Zutectrathan you should
There are no known consequences of an overdose. However, if you have used more than the prescribed dose of Zutectra, contact your doctor, healthcare professional or pharmacist straight away for advice.

If you miss your usual dose
Do not take a double dose to make up for a forgotten injection. Talk to your doctor about managing the dose. Your doctor will tell you how much and how often you need to use Zutectra.

Make sure you use Zutectra as prescribed and as instructed by your doctor to avoid the risk of a

hepatitis B re-infection.

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

The frequency of possible side effects listed below is defined using the following convention: very common (affects more than 1 user in 10)
common (affects 1 to 10 users in 100)
uncommon (affects 1 to 10 users in 1,000)
rare (affects 1 to 10 users in 10,000)
very rare (affects less than 1 user in 10,000)
not known (frequency cannot be estimated from the available data).

If you notice any of the following effects, tell your doctor immediately:

• rash,
• itching,
• wheezing,
• difficulty in breathing,
• swelling of the eyelids, face, lips, throat or tongue,
• low blood pressure, fast pulse

This can be an allergic reaction (hypersensitivity reaction) or a serious allergic reaction (anaphylactic shock).

The following side effects have been reported:

Common (likely to occur in more than 1 in 100 but less than 1 in 10 patients):

• injection site reactions: pain, hives (urticaria), haematoma (a collection of blood in tissue under the skin)

Uncommon (likely to occur in more than 1 in 1 000 but less than 1 in 100 patients):

• headache
• upper abdominal pain (from your chest to the belly button)

Furthermore the following single case reports have been reported:

• fatigue
• tiredness

With other human immunoglobulin preparations the following additional symptoms have been reported:

• chills,
• headache,
• fever,
• vomiting,
• mild hypersensitivity reactions (allergic reactions),
• nausea (urge to vomit),
• joint pain,
• low blood pressure,
• moderate low back pain

The following local reactions at the injection site may occur: swelling, soreness, redness, hardening of the skin, local heat, itching, bruising and rash.

You must closely monitor and carefully observe yourself for any symptoms throughout the injection. Any injection-related adverse events should be treated by stopping the injection and you must speak to your doctor immediately.

Please tell your doctor, healthcare professional or pharmacist:

if any of the side effects gets serious, or if you notice a side effect not listed in this leaflet.

• Keep out of the reach and sight of children.
• Do not use Zutectra after the expiry date which is stated on the outer carton and the syringe label after EXP. The expiry date refers to the last day of that month.
• Store and transport refrigerated (2°C-8°C).
• Do not freeze.
• Keep the container in the outer carton in order to protect from light.
• Zutectra must be brought to room temperature (approx. 23°C-27°C) before use. The solution should be administered immediately after opening the syringe.
• Do not use Zutectra if you notice that the solution is cloudy or has particles.
• Any unused medicine or waste material should be disposed of in accordance with local requirements. Once the injection has been completed, dispose of all needles, syringes and empty glass containers without delay in a container intended for sharp objects you were provided with.

What Zutectra contains

• The active substance of Zutectra is human hepatitis B immunoglobulin 500 IU/ml.
• Zutectra contains 150 mg/ml of human plasma protein of which at least 96 % is immunoglobulin G (IgG). The maximum immunoglobulin A (IgA) content is 6 mg/ml.
• The other ingredients are glycine and water for injections.

What Zutectra looks like and the contents of the pack

Zutectra is presented as a solution for injection provided in pre-filled syringes (500 IU/ml - pack size of 5 in a blister). The colour of the solution can vary from clear to pale yellow or light brown.

One pre-filled syringe of 1 ml Zutectra contains 500 IU. Zutectra is supplied in a pack size containing 5 pre-filled syringes each in a blister pack.

Marketing Authorisation Holder and Manufacturer

Biotest Pharma GmbH

Landsteinerstrasse 5
D-63303 Dreieich
Germany
Tel.: + 49 6103 801-0
Fax: + 49 6103 801-150 / -727

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

BelgiëBelgiqueBelgien Infarama bvba Costermansstede 1 LuxembourgLuxemburg Biotest AG Landsteinerstr. 5

B-1850 Grimbergen TélTel 32 22709522 D-63303 Dreieich TélTel 49 6103 801-0

. 33-35 1606 Te. 359 2 953 1224 Magyarország Biotest Hungaria Kft. Torbágy u. 15A H-2045 Törökbálint Tel. 36 23 511 311

eská republika Reg-Pharm spol.s.r.o. Fialková 45 CZ-10600 Praha 10 Tel 420 2 7265 4004 Malta Rodel Ltd 55, Ravina Triq ir-Russett MT-Kappara SGN 4432 Tel 356 27 386221

Danmark Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 Nederland Infarama bvba Costermansstede 1 B-1850 Grimbergen Tel 32 22709522

Deutschland Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 Norge Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0

Eesti Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 Österreich Biotest Austria GmbH Einsiedlergasse 58 A-1053 Wien Tel 43 1 545 15 61-0

BIOTEST ... 25, GR-151 26 30 210 8043-437 Polska Nobipharm Sp. Z.o.o. ul Rydygiera 8 PL01-793 Warszawa Tel. 48 22 8322638

España Biotest Medical, S.L.U. CBeethoven, 15, 4a Planta ES-08021 Barcelona Tel 34 931 838 734 Portugal SPCare Especialidades Farmacêuticas, Lda Rua Luciano Cordeiro, n 123, 1 dto. PT-1600 139 Lisboa Tel 351 21 193 14 20

France Biotest S.a.r.l. 375 rue Morane Saulnier, BP 65 F-78534 Buc Cedex Tél 33 1 3920 2080 România HK ZY Best Pharma Distribution SRL. Str General tefan Burileanu, nr 8 Bucharest 013762 - RO Tel 40 21 4109494

Ireland Intrapharma Ltd. Pharmaceutical Suppliers Unitech House Magna Business Park, Slovenija Blood Transfusion Centre of Slovenia BTC Slajmerjeva 6

SI-1000 Ljubljana Tel 386 1 54 38 100 Magna Drive, Citywest Road IRL-Dublin 24 Tel 353 1 404 8344

Ísland Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 Slovenská republika Reg-Pharm spol.s.r.o. Fialková 45 CZ-10600 Praha 10 Tel 420 2 7265 4004

Italia Biotest Italia S.r.l. Via Leonardo da Vinci 43 I-20090 Trezzano sul Naviglio Tel 39 02 4844 2951 SuomiFinland Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0

Sverige Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 . . . 22578 1522 357 22 611 038

Latvija Biotest AG Landsteinerstrasse 5 D-63303 Dreieich Tel 49 6103 801-0 United Kingdom Biotest UK Ltd. 28 Monkspath Business Park, Highlands Road, Shirley, Solihull West Midlands B90 4NZUK Tel 44 121 733 3393

Lietuva
Biotest AGLandsteinerstrasse 5
D-63303 Dreieich
Tel: + 49 6103 801-0

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HOW TO INJECT ZUTECTRA BY YOURSELF OR BY CAREGIVER

The following instructions are intended to explain how to inject Zutectra. Please read the instructions carefully and follow them step by step. The doctor or his/her assistant will teach you the process of administration.

Do not attempt to inject Zutectra until you are sure that you understand how to prepare the injection solution and give the injection.

General information:

• Keep the syringes and syringe disposal unit out of the reach of children; lock the supplies if possible.
• Try to take the injection at the same time of day. This makes it easier to remember it.
• Always double-check the dosage.
• The solution must be brought to room temperature before use.
• Open each syringe only when you are ready for an injection. You should administer the injection immediately after opening the syringe.
• The colour of the solution can vary from clear to pale yellow up to light brown. Do not use solutions that are cloudy or have particles.
• This medicine must not be mixed with other medicines.

Before the injection:

1. Wash your hands. It is important to have your hands and the items you use as clean as possible.

2. Lay out everything you need in advance. Find a clean place where you can spread out all the items

you are going to use:

• two alcohol swabs,
• one syringe of Zutectra,
• one needle suitable for subcutaneous injection.

Please note that alcohol swabs and needles are not contained in the pack and you need to supply them yourself.

3. Before preparing the injection, decide where you are going to inject. You should inject Zutectra into

the fatty layer between the skin and muscle (about 8 to 12 mm under the skin). The best places for injections are where the skin is loose and soft for example in the abdomen, arm, thigh or buttocks, and away from joints, nerves, bones.

Important: Do not use on any area where you can feel lumps, bumps, firm knots, pain or on an area that is discoloured, indented, scabbed, or where the skin is broken. Talk to the doctor or healthcare professional about these or any other unusual conditions you may find. You should rotate the injection site at every injection. If some areas are too difficult for you to reach, you may need a caregiver to help you with these injections.

4. Prepare the Zutectra syringe:

Take the syringe out of the pack. Examine the solution carefully. It should be clear and contain no particles. If the solution is discoloured, cloudy or contains particles, discard it and start again with a new syringe. Remove the protective cap from the syringe.

Take the needle out of its sterile pack and fit the needle onto the syringe.

5. Get rid of any air bubbles there may be in the syringe.

Hold the syringe with the needle pointing upwards, and tap the syringe gently with your fingers until the air has collected at the tip. Carefully push the plunger in until the air bubbles have disappeared.

Injection

1. Choose the area where you will make the injection and make a note of it in the diary.

Abdomen stomach Do not use the area within one inch around the navel. Avoid using the belt line area, as rubbing may irritate the injection site. Avoid surgical scars. This is likely to be the easiest place to inject if you are doing it yourself. Thighs Use middle and outer areas where you can pinch up tissue. You are likely to have more fatty tissue the closer you are to the hip and the further you are from the knee. Arms The back of the upper arm should be used. It is hard to pinch up the tissue and inject Zutectra yourself using this site. If you do choose to inject your arm yourself, try to pinch up the tissue by placing your upper arm over the back of a chair or brace it against a wall. It is much easier for someone else to use this site if you do need help. Buttocks Use any area where you can pinch up tissue. Its harder to give yourself an injection here. Try standing in front of a mirror to locate the site or you may want to ask your caregiver to give you the injection.

It's important tochange (rotate) the injection sites. This will help the skin stay supple and help the medicine be absorbed evenly. Rotating sites means starting at one site and using all other sites before going back to the first site you used. Then start the rotation again. It may be helpful to keep a record of where you had the last injection to avoid problems.

The administration in thighs is shown as an example in the following pictures:

2. Wipe the intended area with an alcohol swab. Let the skin air-dry.

3. Gently pinch the skin together around the disinfected injection site to raise it up a little and push the needle into the skin with a rapid, confident movement at an angle of 45 to 90 degrees. Inject beneath the skin as you have been shown by the doctor or nurse.

4. Inject the liquid by pressing gently on the plunger. Allow yourself enough time to inject the whole of the solution until the syringe is empty.

5. Then pull the needle out immediately and let go of the pinched skin.

6. Clean the injection site by wiping it in a circular motion with the alcohol swab.

Dispose of all used items

Once the injection has been completed, dispose of all needles and empty glass containers without delay in a container intended for sharp objects.