Privigen 100 mg/ml solution for infusion

What Privigen is

Privigen is a ready-to-use solution for infusion. The solution contains special proteins, isolated from human blood plasma. These proteins belong to the class of "immunoglobulins", also called antibodies.

How Privigen works

Antibodies are usually produced by our immune system and help the body to fight infections. Certain diseases can cause severe disturbance of the immune system. Because of this, you may not have enough of your own antibodies or you may need additional antibodies. The antibodies which are given to you by Privigen can complement your own antibodies or substitute missing antibodies. The antibodies in Privigen are isolated from human blood plasma. Therefore they work exactly as if they were your own antibodies.
Privigen can also reduce the symptoms in certain inflammatory disorders. In these cases Privigen is regulating the malfunctioning immune system. However, these effects are not fully understood.

What Privigen is used for

Privigen is used in three different situations:

A) Treatment of patients with too few antibodies (replacement therapy). There are three groups:

1. Patients with an inborn lack of antibodies (primary immunodeficiency syndromes (PID)) such as: - congenital agammaglobulinaemia or hypogammaglobulinaemia, - common variable immunodeficiency, - severe combined immunodeficiency,- Wiskott Aldrich syndrome.

2. Patients with certain kinds of blood cancer which lead to a lack of antibody production and recurrent infections such as: - myeloma, - chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia.

3. Children who suffer from inborn AIDS (Acquired Immunodeficiency Syndrome) and recurrent infections.

B) Treatment of patients with certain inflammatory disorders (immunomodulation). There are threegroups:

1. Patients who do not have enough blood platelets (immune thrombocytopenic purpura (ITP)) and - who are at high risk of bleeding, - will have a surgery in the near future.

2. Patients with Guillain-Barré syndrome. This is an acute disease that is characterised by inflammation of the peripheral nerves that causes severe muscle weakness mainly in the legs and upper limbs.

3. Patients with Kawasaki disease. This is an acute disease of primarily young children characterised by an inflammation of the blood vessels throughout the body.

C) Treatment or prevention of infections after a bone marrow transplantation (allogeneic bonemarrow transplantation).

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

Privigen must not be used

If you are allergic hypersensitive to human immunoglobulins, to any other ingredient of Privigen for a complete list of ingredients see section 6 of this leaflet. Please tell your doctor or health care professional prior to treatment about any medicine or food which you have not well tolerated earlier. If you have antibodies against immunoglobulins of the type IgA in your blood. This is very rare and may occur if you do not have enough immunoglobulins of the type IgA in your blood. Please tell your doctor or health care professional prior to treatment if you have an immunoglobulin type IgA deficiency. If you have too much of the amino acid proline in your blood hyperprolinaemia. This is an extremely rare disorder. Only a few families with this disease are known worldwide. Please tell your doctor or health care professional prior to treatment if you have too much proline in your blood.

Take special care with Privigen

The risk of having certain side effects may be increased in the following circumstances you are overweight, you are elderly, you have diabetes, you have been bedridden for a longer time, you have or have already had problems with your blood vessels vascular diseases or blockage of a vessel, you have or have already had kidney problems, you have a high blood pressure, you blood volume is too low hypovolaemia, you suffer from a disease which causes your blood to thicken, you suffer from an increased tendency for blood clotting thrombophilia,

you suffer from a condition that causes low antibody levels in your blood hypogammaglobulinaemia or agammaglobulinaemia, you suffer from a kidney disease, you are taking medicines that can damage your kidneys nephrotoxic medicines, you are receiving Privigen for the first time or after a long break in treatment e.g. several months. Please tell your doctor or health care professional prior to treatment if at least one of these circumstances applies to you. Your doctor will then choose the right intravenous immunoglobulin for you and will take special precautions. Although Privigen does not contain sugar, it may be diluted with a special sugar solution 5 glucose, which could affect your blood sugar level.

You may be allergic hypersensitive to immunoglobulins antibodies without knowing it. This may occur even if you have previously received human immunoglobulins and had tolerated them well. It may happen particularly if you do not have enough immunoglobulins of the type IgA in your blood. In these rare cases allergic reactions such as a sudden fall in blood pressure or shock may occur. If you notice such reactions during the infusion of Privigen, please tell your doctor immediately. He will decide whether to slow down the infusion rate or whether to abort the infusion completely.

For your personal safety the treatment with Privigen will take place under the supervision of your doctor or health care professional. You will usually be observed during the whole infusion and for at least 20 minutes thereafter. In certain circumstances, special precautions may be necessary. Examples of such circumstances are:
- you are receiving Privigen at a high infusion rate or
- you are receiving Privigen for the first time or after a long break in treatment (e.g. several months).
In these cases you will be closely observed during the whole infusion and for at least 1 hour thereafter.

Information on the starting material of Privigen
Privigen 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 products 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 and other types of infections.

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

Immunoglobulins like Privigen have not been associated with hepatitis A or B19 infections. This is possibly because antibodies against these infections are also present in immunoglobulins. These antibodies may help prevent hepatitis A or B19 infections.

It is strongly recommended that every time you receive a dose of Privigen the name and batch number of the product are recorded in order to maintain a record of the batches used.

Taking Privigen with other medicines

Please tell your doctor or health care 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.

Vaccinations
After receiving Privigen, the efficacy of certain vaccinations may be impaired. Affected are vaccinations with live attenuated virus vaccines such as vaccinations against measles, mumps, rubella and varicella. Such vaccinations should be postponed for at least 3 months after the last infusion of Privigen. In the case of measles vaccinations the impairment may persist for up to one year. Therefore your vaccinating doctor should check the efficacy of the measles vaccination.
Please tell your vaccinating doctor prior to a vaccination about your treatment with Privigen.

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

Pregnancy and breast-feeding

Please tell your doctor or health care professional if you are pregnant or breast-feeding. Your doctor will decide whether you can receive Privigen during your pregnancy or while you are breast-feeding.
The use of Privigen in pregnant or breast-feeding women has not been studied separately. Nevertheless, medicines containing antibodies have been used in pregnant or breast-feeding women. The long-time experience showed that no harmful effects on the course of the pregnancy or the newborn are to be expected.

If you receive Privigen while you are breast-feeding the antibodies in this medicine will also be found in the breast milk. Thus also your baby can receive the protecting antibodies.

Driving and using machines

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

Privigen is usually administered by your doctor or health care professional. Privigen is intended solely for the infusion into a vein intravenous infusion. Your doctor decides how much Privigen you will receive. The amount depends on your illness, your present condition and your body weight. At the beginning of the infusion you will receive Privigen at a slow infusion rate. If you tolerate this well your doctor can gradually increase the infusion rate.

If you receive more Privigen than you should

Privigen is usually administered under medical supervision only. Overdose is therefore very unlikely to occur. If, in spite of this, you receive more Privigen than you should, your blood may become too thick (hyperviscous). This may happen particularly if you are a patient at risk, for example if you are elderly or if you suffer from a kidney disease.

Like all medicines, Privigen can cause side effects, although not everybody gets them.

You may be allergic hypersensitive to immunoglobulins antibodies and allergic reactions such as a sudden fall in blood pressure or shock may occur. If you notice such reactions during the infusion of Privigen, please 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 Privigen at a slow infusion rate.

The general experience with immunoglobulin preparations showed that the following side effects may occur headache, chills, fever, vomiting, mild hypersensitivity reactions allergic reactions, nausea, pain in the joints arthralgia, low blood pressure, moderate low back pain.

In rare and isolated cases, the following side effects have also been reported with immunoglobulin preparations temporary non-infectious meningitis reversible aseptic meningitis, transient skin reactions, increase in blood creatinine level, acute renal failure, sudden fall in blood pressure, severe hypersensitivity reactions anaphylactic shock, even when you have shown no hypersensitivity on previous infusions, formation of blood clots which may be carried off in the blood circulation thromboembolic reactions and which may result e.g. in myocardial infarction, stroke, lung vein blockage pulmonary embolism, deep vein thrombosis, transient decrease of red blood cells reversible haemolytic anaemiahaemolysis.

Three clinical studies with Privigen were conducted. In these studies the following side effects have been observed.

The following side effects were common in more than 1 in 100, but less than 1 in 10 infusions headache, vomiting, upset stomach nausea, back pain, chills, tiredness fatigue, fever.

The following side effects were uncommon (in more than 1 in 1000, but less than 1 in 100 infusions): - abnormal awareness of heartbeat,
- temporary lowering of red blood cell count,
- irregularity of red blood cell shape (microscopic finding),

dizziness, head discomfort, sleepiness, shiver tremor, breathlessness, blisters in mouth and throat, painful breathing, throat tightness, diarrhoea, upper stomach pain, protein in the urine on testing, itching, skin disorder, night sweats, hives rash, pain including neck pain, pain in extremity, chest pain, muscle pain, pain and stiffness of muscles and bones muscle spasms, flushing, high or low blood pressure, weakness, flu-like illness, injection site pain, mild jaundice.

Routine laboratory tests may uncommonly reveal changes to liver or kidney functions as well as changes in blood count.

Such side effects may occur even when you have previously received human immunoglobulins (antibodies) and had tolerated them well.

Please tell your doctor or health care professional
- if any of the side effects gets 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 Privigen after the expiry date which is stated on the outer carton and the vial label after EXP. The expiry date refers to the last day of that month.

Do not store above 25 C. Do not freeze. Keep the vial in the outer carton in order to protect from light.

Do not use Privigen if you notice that the solution is cloudy or has particles.

What Privigen contains

The active substance is human normal immunoglobulin antibodies of the type IgG. Privigen contains 100 mgml 10 human protein of which at least 98 is IgG. The other ingredients are the amino acid L-proline and water for injections.

What Privigen looks like and contents of the pack

Privigen is presented as a solution for infusion.
The solution is clear or slightly opalescent and colourless to pale-yellow.

Pack sizes:
1 vial (2.5 g/25 ml, 5 g/50 ml, 10 g/100 ml or 20 g/200 ml),
3 vials (10 g/100 ml or 20 g/200 ml).

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

CSL Behring GmbH

Emil-von-Behring-Strasse 76
D-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 ApS Lyngby Hovedgade 70B, 1.tv DK-2800 Kgs. Lyngby Tlf 45 4520 1420 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-02-819 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 21 327 2614

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 1444 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

-------------------------------------------------------------------------------------------------------------------------- The following information is intended for healthcare professionals only:

Posology and method of administration

The dosage recommendations are summarised in the following table:

Dose Frequency of injections Indication Replacement therapy in primary immunodeficiency starting dose 0.40.8 gkg bw thereafter 0.20.8 gkg bw every two to four weeks to obtain IgG trough levels of at least 46 gl in secondary immunodeficiency 0.20.4 gkg bw every three to four weeks to obtain IgG trough levels of at least 46 gl Children with AIDS 0.20.4 gkg bw every three to four weeks Immunomodulation Immune thrombocytopenic purpura 0.81 gkg bw on day one, possibly repeated once within three days or 0.4 gkg bwd for two to five days Guillain-Barré syndrome 0.4 gkg bwd for three to seven days Kawasaki disease 1.62 gkg bw in divided doses over two to five days in association with acetylsalicylic acid or 2 gkg bw in one dose in association with acetylsalicylic acid Allogeneic bone marrow transplantation 0.5 gkg bw treatment of infections and prophylaxis of graft versus host disease every week from seven days before up to three months after transplantation persistent lack of antibody production 0.5 gkg bw every month until antibody levels return to normal

Method of administration

• Human normal immunoglobulin should be infused intravenously. The initial infusion rate is 0.3 ml/kg bw/hr. If well tolerated, the rate of administration may gradually be increased to 4.8 ml/kg bw/hr.
• In PID patients who have tolerated the infusion rate of 4.8 ml/kg bw/hr well, the rate may be further increased gradually to a maximum of 7.2 ml/kg bw/hr.
• If dilution prior to infusion is desired, Privigen may be diluted with 5% glucose solution to a final concentration of 50 mg/ml (5%). Special precautions
• In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped.
• It is strongly recommended that every time Privigen is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.

Incompatibilities

This medicinal product must not be mixed with other medicinal products

Special precautions for disposal and other handling

• The product should be at room or body temperature before use. A vented infusion line should be used for the administration of Privigen. Always pierce the stopper at its centre, within the marked area.
• The solution should be clear or slightly opalescent. Do not use solutions that are cloudy or have particulate matter.
• If dilution is desired, 5% glucose solution is recommended. For obtaining an immunoglobulin solution of 50 mg/ml (5%), Privigen 100mg/ml (10%) should be diluted with an equal volume of the glucose solution. Aseptic technique must be strictly observed during the dilution of Privigen.
• Once the vial has been entered under aseptic conditions, its contents should be used promptly. Because the solution contains no preservative, Privigen should be infused as soon as possible.
• Any unused product or waste material should be disposed of in accordance with local requirements.