Privigen · 4.6 Fertility, pregnancy and lactation · 1

HOS-094888 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate low back pain may occur occasionally in connection with intravenous administration of human immunoglobulin. 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 and rare cases of transient cutaneous reactions (including cutaneous lupus erythematosus – frequency unknown) have been observed with human normal immunoglobulin. Reversible haemolytic reactions have been observed in patients, especially those with blood groups A, B, and AB in immunomodulatory treatment. Rarely, haemolytic anaemia requiring transfusion may develop after high dose IVIg treatment (see section 4.4). Increase in serum creatinine level and/or acute renal failure have been observed. Very rarely: Transfusion related acute lung injury (TRALI) and thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism and deep vein thromboses. Tabulated list of adverse reactions Seven clinical studies were performed with Privigen, which included patients with PID, ITP and CIDP. In the pivotal PID study, 80 patients were enrolled and treated with Privigen. Of these, 72 completed the 12 months of treatment. In the PID extension study, 55 patients were enrolled and treated with Privigen. Another clinical study included 11 PID patients in Japan. Two ITP studies were performed with 57 patients each. Two CIDP studies were performed with 28 and 207 patients, respectively. 10 Most adverse drug reactions (ADRs) observed in the seven clinical studies were mild to moderate in nature. The following table shows an overview of the ADRs observed in the seven clinical studies categorized according the MedDRA System Organ Class (SOC), Preferred Term Level (PT) and frequency. Frequencies were evaluated according to the following conventions: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10,000 to <1/1,000), Very rare (<1/10,000). For spontaneous post-marketing ADRs, the reporting frequency is categorized as unknown. Within each frequency grouping, undesirable effects are presented in order of decreasing frequency. MedDRA System A

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HOS-094884 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance (human immunoglobulins) or to any of the excipients (see sections 4.4 and 6.1). Patients with selective IgA deficiency who developed antibodies to IgA as administering an IgA- containing product can result in anaphylaxis. Patients with hyperprolinaemia type I or II.

HOS-094883 · has-indication-information · PDF-Seite 2

Replacement therapy in adults, children, and adolescents (0-18 years) in: – Primary immunodeficiency syndromes (PID) with impaired antibody production (see section 4.4). – Secondary immunodeficiencies (SID) in patients who suffer from severe or recurrent infections, ineffective antimicrobial treatment and either proven specific antibody failure (PSAF)* or serum IgG level of <4 g/l. 2 * PSAF = failure to mount at least a 2-fold rise in IgG antibody titre to pneumococcal polysaccharide and polypeptide antigen vaccines. Measles pre-/post exposure prophylaxis for susceptible adults, children and adolescents (0-18 years) in whom active immunisation is contraindicated or not advised. Consideration should also be given to official recommendations on intravenous human immunoglobulin use in measles pre-/post exposure prophylaxis and active immunisation. Immunomodulation in adults, children, and adolescents (0-18 years) in: – Primary immune thrombocytopenia (ITP), in patients at high risk of bleeding or prior to surgery to correct the platelet count. – Guillain-Barré syndrome. – Kawasaki disease (in conjunction with acetylsalicylic acid; see section 4.2.). – Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Only limited experience is available of use of intravenous immunoglobulins in children with CIDP. – Multifocal motor neuropathy (MMN).

HOS-094886 · has-interaction-information · PDF-Seite 9

Live attenuated virus vaccines Immunoglobulin administration may impair for a period of at least 6 weeks and up to 3 months the efficacy of live attenuated virus vaccines such as measles, rubella, mumps, and varicella. After administration of this medicinal product, an interval of 3 months should elapse before vaccination with live attenuated virus vaccines. In the case of measles, this impairment may persist for up to 1 year. Therefore, patients receiving measles vaccine should have their antibody status checked. Loop diuretics Avoidance of concomitant use of loop diuretics. Paediatric population Although limited data is available, it is expected that the same interactions may occur in the paediatric population.

HOS-094887 · has-pregnancy-information · PDF-Seite 9

Pregnancy 9 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. IVIg products have been shown to cross the placenta, increasingly during the third trimester. 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. Experimental studies of the excipient L-proline carried out in animals found no direct or indirect toxicity affecting pregnancy, embryonal or foetal development. Breast-feeding Immunoglobulins are excreted into the milk and may contribute to protecting the neonate from pathogens which have a mucosal portal of entry. Fertility Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be expected.

HOS-094885 · has-warning-information · PDF-Seite 6

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Certain severe adverse reactions may be related to the rate of infusion. The recommended infusion rate given under section 4.2 must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period. Certain adverse reactions may occur more frequently: – in case of high rate of infusion, – in patients with hypogammaglobulinaemia 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. 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 the first hour after the first infusion, in order to detect potential adverse signs. All other patients should be observed for at least 20 minutes after administration. 6 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 adverse reaction. 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 (see section 4.5.). For patients suffering from diabetes mellitus and requiring dilution of Privigen to lower concentrations, the presence of glucose in the recommended diluent should be taken into account. Hypersensitivity True hypersensitivity reactions are rare. They can occur in patients with anti-IgA antibodies. IVIg is not indicated in patients with selective IgA deficiency where the IgA deficiency is the only abnormality

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