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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

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1. NAME OF THE MEDICINAL PRODUCT Privigen 100 mg/ml solution for infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Human normal immunoglobulin (IVIg). One ml contains: human plasma protein…………………………………………………………………………...100 mg (purity of at least 98% IgG) One vial of 50 ml contains: 5 g One vial of 100 ml contains: 10 g One vial of 200 ml contains: 20 g Distribution of the IgG subclasses (average values): IgG1 ............. 67.8% IgG2 ............. 28.7% IgG3 ............. 2.3% IgG4 ............. 1.2% The maximum IgA content is 0.025 mg/ml (average of 0.0027 mg/ml). For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Solution for infusion. The solution is clear or slightly opalescent and colourless to pale yellow. Privigen is isotonic, with an osmolality of 320 mOsmol/kg. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Replacement therapy in • Primary immunodeficiency (PID) syndromes such as:

– congenital agammaglobulinaemia and hypogammaglobulinaemia – common variable immunodeficiency – severe combined immunodeficiency – Wiskott Aldrich syndrome

• Myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.

• Children with congenital AIDS and recurrent infections. Immunomodulation • Immune thrombocytopenic purpura (ITP), in children or adults at high risk of bleeding or prior

to surgery to correct the platelet count. • Guillain-Barré syndrome. • Kawasaki disease.

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Allogeneic bone marrow transplantation 4.2 Posology and method of administration Posology The dose and dosage regimen is dependent on the indication. In replacement therapy the dosage may need to be individualised for each patient depending on the pharmacokinetic and clinical response. The following dosage regimens are given as a guideline. Replacement therapy in primary immunodeficiency syndromes The dosage regimen should achieve a trough IgG level (measured before the next infusion) of at least 4 to 6 g/l. Three to six months are required after the initiation of therapy for equilibration to occur. The recommended starting dose is 0.4 to 0.8 g/kg body weight (bw) followed by at least 0.2 g/kg bw every three weeks. The dose required to achieve a trough level of 6 g/l is of the order of 0.2 to 0.8 g/kg bw/month. The dosage interval when steady state has been reached varies from two to four weeks. Trough levels should be measured in order to adjust the dose and dosage interval. Replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections; replacement therapy in children with AIDS and recurrent infections The recommended dose is 0.2 to 0.4 g/kg bw every three to four weeks. Immune thrombocytopenic purpura For the treatment of an acute episode, 0.8 to 1 g/kg bw on day one, which may be repeated once within three days, or 0.4 g/kg bw daily for two to five days. The treatment can be repeated if relapse occurs. Guillain-Barré syndrome 0.4 g/kg bw/day for three to seven days. Experience in children is limited. Kawasaki disease 1.6 to 2.0 g/kg bw should be administered in divided doses over two to five days or 2.0 g/kg bw as a single dose. Patients should receive concomitant treatment with acetylsalicylic acid. Allogeneic bone marrow transplantation: Human normal immunoglobulin treatment can be used as part of the conditioning regimen and after the transplantation. For the treatment of infections and prophylaxis of graft versus host disease, dosage is individually tailored. The starting dose is normally 0.5 g/kg bw/week, starting seven days before transplantation and continued for up to three months after the transplantation. In case of persistent lack of antibody production, a dose of 0.5 g/kg bw/month is recommended until antibody levels return to normal. The dosage recommendations are summarised in the following table:

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Indication Dose Frequency of injections Replacement therapy – in primary immunodeficiency – in secondary immunodeficiency – Children with AIDS

starting dose:

0.4–0.8 g/kg bw

thereafter: 0.2–0.8 g/kg bw

0.2–0.4 g/kg bw

0.2–0.4 g/kg bw

every two to four weeks to obtain IgG trough levels of at least 4–6 g/l every three to four weeks to obtain IgG trough levels of at least 4–6 g/l every three to four weeks

Immunomodulation – Immune thrombocytopenic purpura – Guillain-Barré syndrome – Kawasaki disease

0.8–1 g/kg bw

or 0.4 g/kg bw/d

0.4 g/kg bw/d

1.6–2 g/kg bw

or 2 g/kg bw

on day one, possibly repeated once within three days for two to five days for three to seven days in divided doses over two to five days in association with acetylsalicylic acid in one dose in association with acetylsalicylic acid

Allogeneic bone marrow transplantation – treatment of infections and prophylaxis

of graft versus host disease – persistent lack of antibody production

0.5 g/kg bw

0.5 g/kg bw

every week from seven days before up to three months after transplantation 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 a clinical study in PID patients, the maximum infusion rate was 7.2 ml/kg bw/hr. 4.3 Contraindications Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to homologous immunoglobulins, especially in the very rare cases of IgA deficiency when the patient has antibodies against IgA. Patients with hyperprolinaemia. 4.4 Special warnings and precautions for use Certain severe adverse drug reactions may be related to the rate of infusion. The recommended infusion rate given under section 4.2 "Method of administration" must be followed closely. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.

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Certain adverse reactions may occur more frequently: – in case of high rate of infusion, – in patients with hypo- or agammaglobulinaemia with or without IgA deficiency, – in patients who receive human normal immunoglobulin for the first time or, in rare cases, when

the human normal immunoglobulin product is switched or when there has been a long interval since the previous infusion.

True hypersensitivity reactions are rare. They can occur in the very rare cases of IgA deficiency with anti-IgA antibodies. Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who had tolerated previous treatment with human normal immunoglobulin. Potential complications can often be avoided by ensuring that patients: – are not sensitive to human normal immunoglobulin by initially infusing the product slowly

(0.3 ml/kg bw/hr); – are carefully monitored for any symptoms throughout the infusion period. In particular, patients

naive to human normal immunoglobulin, patients switched from an alternative IVIg product or when there has been a long interval since the previous infusion should be monitored during the first infusion and for one hour after, in order to detect potential adverse signs. All other patients should be observed for at least twenty minutes after administration.

There is clinical evidence of an association between IVIg administration and thromboembolic events such as myocardial infarction, stroke, pulmonary embolism and deep vein thromboses which is assumed to be related to a relative increase in blood viscosity through the high influx of immunoglobulin in at-risk patients. Caution should be exercised in prescribing and infusing IVIg in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of immobilisation, severely hypovolaemic patients and patients with diseases which increase blood viscosity). Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolaemia, being overweight, concomitant nephrotoxic medicinal products or age over 65. In case of renal impairment, IVIg discontinuation should be considered. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IVIg products, those containing sucrose as a stabiliser accounted for a disproportionate share of the total number. In patients at risk, the use of IVIg products that do not contain sucrose may be considered. Privigen does not contain sucrose or other sugars. In patients at risk of acute renal failure or thromboembolic adverse reactions, IVIg products should be administered at the minimum rate of infusion and dose practicable. In all patients, IVIg administration requires: – adequate hydration prior to the initiation of the infusion of IVIg – monitoring of urine output – monitoring of serum creatinine levels – avoidance of concomitant use of loop diuretics. In case of adverse reaction, either the rate of administration must be reduced or the infusion stopped. The treatment required depends on the nature and severity of the side effect. In case of shock, standard medical treatment for shock should be implemented. Information on safety with respect to transmissible agents Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the

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inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens. The measures taken are considered effective for enveloped viruses such as HIV, HBV, and HCV, and for the non-enveloped viruses HAV and B19V. There is reassuring clinical experience regarding the lack of hepatitis A or B19V transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety. 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. 4.5 Interaction with other medicinal products and other forms of interaction Live attenuated virus vaccines Immunoglobulin administration may impair the efficacy of live attenuated virus vaccines such as measles, mumps, rubella and varicella for a period of at least six weeks and up to three months. After administration of this product, an interval of three months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to one year. Therefore patients receiving measles vaccine should have their antibody status checked. Interference with serological testing After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing. Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D, may interfere with some serological tests for red cell allo-antibodies (e.g. Coombs test). 4.6 Pregnancy and lactation The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and therefore should only be given with caution to pregnant women and breast-feeding mothers. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected. Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate. 4.7 Effects on ability to drive and use machines No effects on ability to drive and use machines have been observed. 4.8 Undesirable effects With human normal immunoglobulin for intravenous administration, adverse reactions such as chills, headache, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain may occur occasionally. Rarely human normal immunoglobulins may cause a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration. Cases of reversible aseptic meningitis, isolated cases of reversible haemolytic anaemia/haemolysis and rare cases of transient cutaneous reactions, have been observed with human normal immunoglobulin.

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Increase in serum creatinine level and/or acute renal failure have been observed. Very rarely: Thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism and deep vein thromboses. Two clinical studies with Privigen were performed, one in patients with primary immunodeficiency (PID) and one in patients with immune thrombocytopenic purpura (ITP). In the PID study 80 subjects were enrolled and treated with Privigen. Of these, 72 completed the twelve months of treatment. The ITP study was performed in 57 patients. Most adverse drug reactions (ADRs) observed in the two clinical studies were mild to moderate in nature. The ADRs reported in the two studies are summarised and categorised according to the MedDRA System organ class and frequency below. Frequency per infusion has been evaluated using the following criteria: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1 000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing severity. Frequency of Adverse Drug Reactions (ADRs) in clinical studies with Privigen MedDRA System Organ Class

MedDRA preferred term ADR frequency category

Investigations Bilirubin conjugated increased, blood bilirubin unconjugated increased, Coombs direct test positive, Coombs test positive, blood lactate dehydrogenase increased, haematocrit decreased, alanine aminotransferase increased, aspartate aminotransferase increased, blood creatinine increased, blood pressure decreased, blood pressure increased, body temperature increased, haemoglobin decreased

Uncommon

Blood and lymphatic system disorders

Anaemia, anisocytosis Uncommon

Headache Very common Nervous system disorders Dizziness, head discomfort, somnolence, tremor Uncommon

Respiratory, thoracic and mediastinal disorders

Dyspnoea Uncommon

Vomiting, nausea Common Gastrointestinal disorders Diarrhoea Uncommon

Renal and urinary disorders

Proteinuria Uncommon

Skin and subcutaneous tissue disorders

Pruritus, skin disorder Uncommon

Musculoskeletal and connective tissue disorders

Back pain, neck pain, pain in extremity, musculoskeletal stiffness

Uncommon

Chills, fatigue, pyrexia Common General disorders and administration site conditions

Chest pain, general symptom, asthenia, influenza like illness, hyperthermia, pain

Uncommon

Hepatobiliary disorders Hyperbilirubinaemia Uncommon For safety with respect to transmissible agents, see section 4.4.

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4.9 Overdose Overdose may lead to fluid overload and hyperviscosity, particularly in patients at risk, including elderly patients or patients with renal impairment. 5. PHARMACOLOGICAL PROPERTIES 5.1 Pharmacodynamic properties Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, for intravascular administration, ATC code: J06BA02. Human normal immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents. Human normal immunoglobulin contains the IgG antibodies present in the normal population. It is usually prepared from pooled plasma from not fewer than 1,000 donors. It has a distribution of immunoglobulin G subclasses closely proportional to that in native human plasma. Adequate doses of this medicinal product may restore abnormally low immunoglobulin G levels to the normal range. The mechanism of action in indications other than replacement therapy is not fully elucidated, but includes immunomodulatory effects. The safety and efficacy of Privigen was evaluated in two prospective, open-label, single-arm, multicenter studies performed in Europe (ITP study) and Europe and USA (PID study). 5.2 Pharmacokinetic properties Human normal immunoglobulin is immediately and completely bioavailable in the recipient's circulation after intravenous administration. It is distributed relatively rapidly between plasma and extravascular fluid, equilibrium between the intra- and extravascular compartments is reached after approximately three to five days. The pharmacokinetic parameters for Privigen were determined in a clinical study in PID patients (see section 5.1). Twenty-five patients (aged 13 to 69 years) participated in the pharmacokinetic assessment (see table below). The median half-life of Privigen in primary immunodeficiency patients was 36.6 days. This half-life may vary from patient to patient, particularly in primary immunodeficiency. Pharmacokinetic parameters of Privigen in 25 PID patients Parameter Median (Range) Cmax (peak, g/l) 23.4 (10.4-34.6) Cmin (trough, g/l) 10.2 (5.8-14.7) t½ (days) 36.6 (20.6-96.6) Cmax, maximum serum concentration; Cmin, trough (minimum level) serum concentration; t½, elimination half-life IgG and IgG-complexes are broken down in cells of the reticuloendothelial system. 5.3 Preclinical safety data Immunoglobulins are a normal constituent of the human body. L-proline is a physiological, non-essential amino acid.

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The safety of Privigen has been assessed in several preclinical studies, with particular reference to the excipient L-proline. Some published studies pertaining to hyperprolinaemia have shown that long-term, high doses of L-proline have effects on brain development in very young rats. However, in studies where the dosing was designed to reflect the clinical indications for Privigen, no effects on brain development were observed. Non-clinical data reveal no special risk for humans based on safety pharmacology and toxicity studies. 6. PHARMACEUTICAL PARTICULARS 6.1 List of excipients L-proline Water for injections 6.2 Incompatibilities This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6. 6.3 Shelf life 2 years 6.4 Special precautions for storage Do not store above 25 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light. 6.5 Nature and contents of container 50 or 100 ml of solution in a single vial (type I or II glass), with a stopper (elastomeric), a cap (aluminium crimp), a flip off disc (plastic), label with integrated hanger. 200 ml of solution in a single vial (type II glass), with a stopper (elastomeric), a cap (aluminium crimp), a flip off disc (plastic), label with integrated hanger. Pack size: 1 vial. Not all pack sizes may be marketed. 6.6 Special precautions for disposal and other handling Privigen comes as a ready-for-use solution in single-use vials. 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. 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.

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7. MARKETING AUTHORISATION HOLDER CSL Behring GmbH Emil-von-Behring-Strasse 76 D-35041 Marburg Germany 8. MARKETING AUTHORISATION NUMBERS 9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 10. DATE OF REVISION OF THE TEXT Detailed information on this product is available on the website of the European Medicines Agency (EMEA): http://www.emea.europa.eu/

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ANNEX II A. MANUFACTURER OF THE BIOLOGICAL ACTIVE

SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OF THE MARKETING AUTHORISATION

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A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer(s) of the biological active substance(s) CSL Behring AG Wankdorfstrasse 10, 3000 Bern 22 Switzerland Name and address of the manufacturer(s) responsible for batch release CSL Behring GmbH Emil-von-Behring-Strasse 76 D-35041 Marburg Germany The printed package leaflet of the medicinal product must state the name and address of the manufacturer responsible for the release of the concerned batch. B. CONDITIONS OF THE MARKETING AUTHORISATION • CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON

THE MARKETING AUTHORISATION HOLDER Medicinal product subject to medical prescription. • OTHER CONDITIONS Pharmacovigilance system The MAH must ensure that the system of pharmacovigilance, as described in version 1.0 presented in Module 1.8.1. of the Marketing Authorisation Application, is in place and functioning before and whilst the product is on the market. Risk Management Plan The MAH commits to performing the studies and additional pharmacovigilance activities detailed in the Pharmacovigilance Plan, as agreed in version 1.3 of the Risk Management Plan (RMP) presented in Module 1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by the CHMP. As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the updated RMP should be submitted at the same time as the next Periodic Safety Update Report (PSUR). In addition, an updated RMP should be submitted

• When new information is received that may impact on the current Safety Specification, Pharmacovigilance Plan or risk minimisation activities

• Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being reached

• At the request of the EMEA Official batch release: in accordance with Article 114 Directive 2001/83/EC as amended, the official batch release will be undertaken by a state laboratory or a laboratory designated for that purpose.

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ANNEX III

LABELLING AND PACKAGE LEAFLET

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A. LABELLING

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PARTICULARS TO APPEAR ON THE OUTER PACKAGING OUTER BOX 1. NAME OF THE MEDICINAL PRODUCT Privigen 100 mg/ml solution for infusion Human normal immunoglobulin (IVIg) 2. STATEMENT OF ACTIVE SUBSTANCE(S) One ml contains: Human plasma protein.............100 mg IgG purity ................................. ≥ 98% IgA.....................................≤ 0.025 mg 5 g/50 ml 10 g/100 ml 20 g/200 ml Will be placed in the upper right corner of the main face of the box to give total content and volume of the container 3. LIST OF EXCIPIENTS Excipients: L-proline, water for injections. 4. PHARMACEUTICAL FORM AND CONTENTS Solution for infusion (10%) Contains 1 vial. 5. METHOD AND ROUTE(S) OF ADMINISTRATION For intravenous use only. Read the package leaflet before use. 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 8. EXPIRY DATE EXP

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9. SPECIAL STORAGE CONDITIONS Do not store above 25 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light. 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER Marketing authorisation holder: CSL Behring GmbH Emil-von-Behring-Strasse 76 D-35041 Marburg Germany 12. MARKETING AUTHORISATION NUMBER(S) 13. BATCH NUMBER LOT 14. GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to medical prescription. 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted.

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PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGING VIAL 1. NAME OF THE MEDICINAL PRODUCT Privigen 100 mg/ml solution for infusion Human normal immunoglobulin (IVIg) 2. STATEMENT OF ACTIVE SUBSTANCE(S) One ml contains: Human plasma protein: 100 mg; IgG purity: ≥ 98%. IgA: ≤ 0.025 mg. 5 g/50 ml 10 g/100 ml 20 g/200 ml Will be placed in the upper right corner of the label to give total content and volume of the container 3. LIST OF EXCIPIENTS L-proline, water for injections. 4. PHARMACEUTICAL FORM AND CONTENTS Solution for infusion (10%) 5. METHOD AND ROUTE(S) OF ADMINISTRATION For intravenous use only. Read the package leaflet before use. 6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE REACH AND SIGHT OF CHILDREN Keep out of the reach and sight of children. 7. OTHER SPECIAL WARNING(S), IF NECESSARY 8. EXPIRY DATE EXP

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9. SPECIAL STORAGE CONDITIONS Do not store above 25 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light. 10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER CSL Behring GmbH, D-35041 Marburg, Germany 12. MARKETING AUTHORISATION NUMBER(S) 13. BATCH NUMBER LOT 14. GENERAL CLASSIFICATION FOR SUPPLY Medicinal product subject to medical prescription. 15. INSTRUCTIONS ON USE 16. INFORMATION IN BRAILLE Justification for not including Braille accepted.

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B. PACKAGE LEAFLET

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PACKAGE LEAFLET: INFORMATION FOR THE USER

Privigen 100 mg/ml (10%) solution for infusion Human normal immunoglobulin (IVIg)

Read all of this leaflet carefully before you start using this medicine. - Keep this leaflet. You may need to read it again. - If you have any further questions, ask 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,

please tell your doctor or health care professional. In this leaflet: 1. What Privigen is and what it is used for 2. Before you receive Privigen 3. How to use Privigen 4. Possible side effects 5. How to store Privigen 6. Further information 1. WHAT PRIVIGEN IS AND WHAT IT IS USED FOR 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.

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

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

groups: 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 bone

marrow transplantation). 2. BEFORE YOU RECEIVE PRIVIGEN

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),

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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.

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 preventing 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.

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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. 3. HOW TO USE PRIVIGEN 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. 4. POSSIBLE SIDE EFFECTS 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.

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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 anaemia/haemolysis) 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.

5. HOW TO STORE PRIVIGEN 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.

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6. FURTHER INFORMATION What Privigen contains The active substance is human normal immunoglobulin (antibodies of the type IgG). Privigen

contains 100 mg/ml (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 size of 1 vial (5 g/50 ml, 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: België/Belgique/Belgien CSL Behring NV Technologielaan 13 B-3001 Leuven Tél/Tel: +32 16 38 80 80

Luxembourg/Luxemburg CSL Behring NV Technologielaan 13 B-3001 Leuven Tél/Tel: +32 16 38 80 80

България CSL Behring GmbH Emil-von-Behring-Strasse 76 D-35041 Marburg Teл.: +49 64 213 93654

Magyarország Plazmed Kft. Fő u. 200 H-2193 Galgahévic Tel.: +36 28 59 10 00

Česká republika IBP medica s.r.o. Pod Karlovem 8/1670 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 06 Luqa Tel: +356 2144 2010

Danmark CSL Behring ApS Lyngby Hovedgade 70B, 1.tv DK-2880 Kgs. Lyngby Tlf: +45 4520 1420

Nederland CSL Behring NV Claudius Prinsenlaan 128 NL-4818 CP Breda Tel: + 31 076 523 6045

Deutschland Wissenschaftliche Hotline CSL Behring GmbH Philipp-Reis-Str. 2

Norge CSL Behring AB P.O.Box 712 S-182 17 Danderyd

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D-65795 Hattersheim Tel: +49 69 305 84437

Tlf: +46 8 544 966 70

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

Österreich CSL Behring GmbH Altmannsdorfer Straße 104 A-1121 Wien Tel: +43 1 80101 2463

Ελλάδα CSL Behring ΜΕΠΕ Mιχαλακοπούλου 35 GR-115 28 Αθήνα Τηλ: +30 210 7255 660

Polska Imed Poland sp. z.o.o. 3, Duchnicka ulica PL-01 796 Warszawa Tel.: +48 22 663 43 10

España CSL Behring S.A. Av Païssos Catalans 34 3º E-08950 Esplugues de Llobregat (Barcelona) Tel: +34 933 67 1870

Portugal CSL Behring Lta. Av 5 de Outubro, 198 – 3ºEsq. 1dto. P-1050-064 Lisboa Tel: +351 21 782 62 30

France CSL Behring 44 rue Cambronne F-75015 Paris Tél: + 33 1 53 58 54 00

România Prisum International Trading srl Strada Magura Vulturului 34 Sector 2 Bucureşti 021701 – RO Tel: +40 21 250 3688

Ireland CSL Behring Hayworth House, Market Place Haywards Heath RH16 1DB – UK Tel: +44 1444 447400

Slovenija MediSanus d.o.o. Vagajeva ulica 4 SI-1000 Ljubljana Tel: +386 1 518 33 97

Ísland CSL Behring AB P.O.Box 712 S-182 17 Danderyd 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. P.le Stefano Türr, 5 I-20149 Milano Tel: +39 02 34964 200

Suomi/Finland CSL Behring AB P.O.Box 712 S-182 17 Danderyd Puh/Tel: +46 8 544 966 70

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Κύπρος ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ ΛΤΔ Γ. Κρανιδιώτη 4 CY-1522 Λευκωσία Τηλ: +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 Tel: +46 8 544 966 70

United Kingdom CSL Behring Hayworth House, Market Place Haywards Heath RH16 1DB – UK Tel: +44 1444 447400

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

This leaflet was last approved in. Detailed information on this medicine is available on the European Medicines Agency (EMEA) web site: http://www.emea.europa.eu/.