Replacement therapy in
• Primary immunodeficiency syndromes (PID) 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 surgical interventions to correct the platelet count
• Guillain-Barré syndrome
• Kawasaki disease
• Chronic inflammatory demyelinating polyneuropathy (CIDP)
Allogeneic bone marrow transplantation

The dosage 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 5 to 6 g/l. Three to 6 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 3 to 4 weeks.
The dose required to achieve a trough level of 5 to 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 3 to
4 weeks. Trough levels should be measured in order to adjust the dose and dosage interval.
Replacement therapy in myelomas or chronic lymphocytic leukaemia with severe secondary
hypogammaglobulinaemia and recurrent infections; replacement therapy in children with
congenital AIDS and recurrent infections
The recommended dosage is 0.2 to 0.4 g/kg bw every 3 to 4 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 3 days, or 0.4 g/kg bw daily for 2 to 5 days. The treatment can be repeated if
relapse occurs (see also section “Properties/Effects”).

Guillain-Barré syndrome
0.4 g/kg bw/day over 5 days. Experience in children is limited.
Kawasaki disease
1.6 to 2.0 g/kg bw should be administered in divided doses over 2 to 5 days or 2.0 g/kg bw as
a single dose. Patients should receive concomitant treatment with acetylsalicylic acid.
Chronic inflammatory demyelinating polyneuropathy (CIDP)
The recommended starting dose is 2 g/kg bw divided over 2 to 5 consecutive days followed
by maintenance doses of 1 g/kg bw given on one day or divided over 2 consecutive days
every 3 weeks.
The long-term therapy over 25 weeks depends on the patient`s response to the maintenance
therapy. The lowest effective maintenance dose and the dosage regimen are to adjust
according to the individual course of the disease.
Allogeneic bone marrow transplantation
Human immunoglobulin therapy can be used as part of the conditioning regimen and after
transplantation. To treat infections and prevent graft-versus-host disease, the dosage should be
individually adjusted.
The starting dosage is usually 0.5 g/kg bw/week, commencing seven days before the
transplant. The treatment is continued for up to 3 months after the transplant. If the lack of
antibody production persists, a dosage of 0.5 g/kg bw/month is recommended until IgG
antibody levels return to normal.

The dosages recommendations are summarised in the following table:

bw = body weight

Use of the product in paediatric population
In the phase III pivotal study on patients with primary immunodeficiency diseases (n = 80),
19 patients between 3 and 11 years of age and 15 patients from 12 up to and including 18
years of age were treated. In an extension study of patients with primary immunodeficiency
diseases (n = 55), 13 patients between 3 and 11 years of age and 11 between 12 and including
18 years of age were treated

Method of administration
Privigen should be infused intravenously.
Rate of infusion
The product should initially be infused at a rate of 0.3 ml/kg bw/hr (for approximately 30
min). If well tolerated, the infusion rate can be gradually increased to 4.8 ml/kg bw/hr. In
patients with immunodeficiency syndrome who have tolerated substitution treatment with
Privigen well, the infusion rate may be gradually increased to a maximal value of 7.2 ml/kg
bw/hr.

Certain severe adverse reactions may be related to the rate of infusion. The recommended
infusion rate given under section “Dosage/Administration: Method of administration” must be
closely followed. Patients must be closely monitored and carefully observed for any
symptoms throughout the infusion period and thereafter.
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, 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.
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 case of shock, standard medical treatment for shock should be implemented.

Higher doses may be associated with increased rates of adverse effects. Therefore, the lowest
effective dose should be sought in individual patients and careful monitoring routine is to
establish.
In all patients, IVIg administration requires adequate hydration prior to the initiation of the
infusion.
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 of concern.
Rarely, human normal immunoglobulin can induce a fall in blood pressure with anaphylactoid
reaction, even in patients who had tolerated previous treatment with human normal
immunoglobulin.
Haemolytic anaemia
IVIg products can contain blood group antibodies (e.g. anti-A and anti-B) which may act as
haemolysins and induce in vivo coating of red blood cells (RBC) with immunoglobulin,
causing a positive direct antiglobulin reaction (Coombs` test) and, rarely, haemolysis.
Haemolytic anaemia can develop subsequent to IVIg therapy due to enhanced RBC
sequestration. The Privigen manufacturing process includes an immunoaffinity chromatography
(IAC) step that specifically reduces blood group A and B antibodies (isoagglutinins A and B). Clinical
data with Privigen manufactured with the IAC step is not available.
Isolated cases of haemolysis-related renal dysfunction/renal failure or disseminated
intravascular coagulation in some cases leading to death have occurred.
The following risk factors are associated with the development of haemolysis: high doses,
whether given as a single administration or divided over several days; blood group A, B and
AB (non-0 blood group) and underlying inflammatory state. As this event was commonly
reported in patients with blood group A, B or AB (non-0 blood group) receiving high doses
for non-PID indications, increased vigilance is recommended.
Haemolysis has rarely been reported in patients given replacement therapy for PID.
IVIg recipients should be monitored for clinical signs and symptoms of haemolysis. If signs
and/or symptoms of haemolysis develop during or after IVIg infusion, discontinuation of IVIg
treatment should be considered by the treating physician (see also section “Undesirable
effects”).

Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome has been reported to occur in association with IVIg treatment.
Discontinuation of IVIg treatment has resulted in remission of AMS within several days
without sequelae. The syndrome usually begins within several hours to 2 days following IVIg
treatment. Cerebrospinal fluid studies are frequently positive with pleocytosis up to several
thousand cells per mm3 (predominantly from the granulocytic series) and elevated protein
levels up to several hundred mg/dl.
AMS may occur more frequently in association with high-dose (2 g/kg) IVIg treatment.

Thromboembolism
There is clinical evidence of an association between IVIg administration and thromboembolic
events such as myocardial infarction, cerebral vascular accident (including 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 immunoglobulins in at-risk patients. Therefore
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, a history of vascular disease or thrombotic episodes, acquired or inherited
thrombophilic disorders, prolonged periods of immobilisation, severe hypovolaemia, diseases
which increase blood viscosity).

In patients at risk for thromboembolic reactions, IVIg products should be administered at the
minimum rate of infusion and minimum dose practicable.
Acute renal failure
Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most
cases risk factors have been identified e.g. pre-existing renal insufficiency, diabetes mellitus,
hypovolaemia, 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 containing various excipients such as sucrose,
glucose and maltose 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 should therefore be considered. Privigen does not contain sucrose, maltose or glucose.
In patients at risk of acute renal failure, IVIg products should be administered at the minimum
rate of infusion and minimum dose practicable.
Transfusion-related acute lung injury (TRALI)
Noncardiogenic pulmonary edema may very rarely occur following treatment with IVIg
products, including Privigen. TRALI is characterized by severe respiratory distress,
pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms
typically appear within 1 to 6 hours following treatment.
Monitor patients for pulmonary adverse reactions. TRALI may be managed using oxygen
therapy with adequate ventilatory support.

Pathogen safety
Privigen is made from human plasma. Because this product is made from human blood, it
may carry a risk of transmitting infectious agents. e.g., viruses, and theoretically, the
Creutzfeldt-Jakob disease (CJD) and Variant Creutzfeldt-Jakob disease (vCJD) agent. There
is also the possibility that unknown infectious agents may be present in such products.
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 inactivation/removal of viruses (see also section
“Properties/Effects”). 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 human
immunodeficiency (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), and for the
non-enveloped viruses such as hepatitis A (HAV) and parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19
transmission with immunoglobulins, and it is also assumed that the antibody content makes an
important contribution to the viral safety.
It is 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.
Sodium content
Privigen is essentially sodium-free (Privigen has a low sodium content of ≤ 1 mmol/l).
Paediatric population
Although limited data is available, it is expected that the same warnings, precautions and risk
factors apply to the paediatric population.

Live attenuated virus vaccines
After treatment with immunoglobulins, the efficacy of live attenuated vaccines, such as
measles, mumps, rubella and chickenpox vaccines, may be impaired for a period of at least 6
weeks and up to 3 months. An interval of 3 months should elapse before vaccination with live
attenuated vaccines. In the case of measles vaccinations, the decrease in efficacy may persist
for up to a year. Patients given measles vaccine should therefore have their antibody status
checked.
Paediatric population
Although limited data is available, it is expected that the same interactions may occur in the
paediatric population.

Pregnancy Category C.
There are no adequate and well-controlled studies in pregnant women. Privigen should be
used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal reproduction studies have not been conducted with Privigen.
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.
Privigen should be given to a pregnant woman only if clearly needed.
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.

The ability to drive and operate machines may be impaired by some adverse reactions
associated with Privigen. Patients who experience adverse reactions during treatment should
wait for these to resolve before driving or operating machines.

Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions,
nausea, arthralgia, low blood pressure, and moderate back pain may occur occasionally in
connection with intravenous administration of human immunoglobulin including Privigen.
Rarely human immunoglobulin including Privigen may cause hypersensitivity reactions with
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 have
been observed with human normal immunoglobulin including Privigen.
Reversible haemolytic reactions have been observed in patients, especially those with blood
groups A, B, and AB (non-0-blood groups) in immunomodulatory treatment. Rarely,
haemolytic anaemia requiring transfusion may develop after high dose IVIg treatment
including Privigen (see section “Warnings and precautions”).
Increase in serum creatinine levels and/or acute renal failure have been observed.
Very rarely: transfusion related acute lung injury and thromboembolic reactions such as
myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis have occurred.

Tabulated list of adverse reactions
Six clinical studies were performed with Privigen, which included patients with PID, ITP and
CIDP patients respectively. In the PID pivotal 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. The two ITP studies were performed with
57 patients each. The two CIDP studies were performed with 28 and 207 patients,
respectively.
Most adverse drug reactions (ADRs) observed in the six clinical studies were mild to
moderate in nature.
The following table shows an overview of the ADRs in the six studies, categorized according
to MedDRA System Organ Class (SOC and Preferred Term Level (PT)) and frequency.
Frequencies per infusion were evaluated according to the following conventions: Very
common (≥ 1/10), Common (≥ 1/100 to < 1/10), Uncommon (≥ 1/1,000 to < 1/100). 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.

For safety with respect to transmissible agents and additional details on risk factors, see
section “Warnings and precautions”.
Paediatric Population
In Privigen clinical studies with paediatric patients, the frequency, nature and severity of
adverse reactions did not differ between children and adults. In postmarketing reports it is
observed that the proportion of haemolysis cases to all case reports occurring in children is
slightly higher than in adults. Please refer to section ”Warnings and precautions” for details
on risk factors and monitoring recommendations.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is
important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Healthcare professionals are asked to report any suspected adverse reactions.

Overdose can lead to fluid volume overload and hyperviscosity, particularly in patients at
risk, including elderly patients or patients with cardiac or renal impairment.

Mechanism of Action/Pharmacodynamics
Privigen is prepared from plasma from 1000 or more human donors. The manufacturing
process for Privigen includes the following steps: ethanol precipitation of the IgG plasma
fraction, followed by octanoic acid fractionation and incubation at pH 4. Subsequent
purification steps comprise depth filtration, chromatography, immunoaffinity chromatography to
specifically reduce blood group A and B antibodies (isoagglutinins A and B) and a filtration step
that can remove particles to a size of 20 nm.
Privigen contains mainly IgG that are present in the normal human population and that show a broad
spectrum of functionally intact antibodies against infectious agents. In the replacement therapy
adequate doses of Privigen may restore abnormally low IgG levels to the normal range.
The IgG subclass distribution in Privigen corresponds roughly to that of native human plasma. Both
the Fc and the Fab functions of the IgG molecules are preserved. The ability of the Fab parts
to bind antigens was demonstrated with biochemical and biological methods. The Fc function
was tested with complement activation and with Fc receptor-mediated leukocyte activation.
The inhibition of immune complex-induced complement activation (“scavenging”, an antiinflammatory
function of IVIgs) is preserved in Privigen. Privigen does not lead to nonspecific
activation of the complement system or of prekallikrein.
The mechanism of action in indications other than replacement therapy is not fully elucidated,
but includes immunomodulatory effects.

Clinical Efficacy
The safety and efficacy of Privigen was investigated in 6 prospective, open, single-arm,
multicentre studies carried out in Europe (ITP, PID and CIDP studies) and in the USA (PID
study). Further data on safety and efficacy were collected in a prospective, open, single-arm,
multicentre extension study with PID patients performed in the USA.
PID
In the pivotal study, 80 patients between 3 and 69 years of age with PID were given a
Privigen infusion at a median dose of 200-888 mg/kg bw every 3 to 4 weeks for at most 1
year. With this treatment, constant IgG trough levels were achieved over the whole of the
treatment period, the mean concentrations being 8.84 g/l to 10.27 g/l. The incidence of acute,
severe bacterial infections (aSBI) was 0.08 per patient per year (the upper 97.5% confidence
limit was 0.182).
As in the pivotal study, Privigen dosages were administered in the PID extension study to a
total of 55 patients (of which 45 had already been treated in the pivotal study and 10 were
newly recruited patients). The results of the pivotal study were confirmed for the average IgG
trough levels (9.31 g/l to 11.15 g/l) and the rate of aSBI (0.018 per patient per year with an
upper 97.5 % confidence interval of 0.098).
ITP
57 patients aged between 15 and 69 years with chronic ITP took part in the ITP study. Their
platelet count at the start was 20 x 109/l. After administration of Privigen at a dose 1 g/kg bw

on two consecutive days, the platelet count rose to at least 50 x 109/l within 7 days of the first
infusion in 80.7% of the patients. In 43% of the patients, this increase occurred after just one
day, before the second infusion. The mean time until this platelet count was reached was 2.5
days. In patients who responded to the treatment, the platelet count remained ≥50 x 109/l for a
mean period of 15.4 days.
In the second ITP study on patients aged between 18 and 65 years, in 42 subjects (74%) the
platelet count increased at least once to ≥50 × 109/l within 6 days after the first infusion,
which was well within the expected range and similar to response rates were reported for
other IVIGs in this indication (70%). A second dose in subjects with platelet counts
≥50 × 109/l after the first dose provided a relevant additional benefit in terms of higher and
longer-lasting increases in platelet counts compared to a single dose. In subjects with platelet
counts <50 × 109/l on day 3 receiving a mandatory second infusion, the lowest median platelet
count (8.0 × 109/l) was observed already at the baseline. In this group, only 30% of subjects
were observed with platelet response after the mandatory second dose. Consequently, it was
more difficult to increase platelet counts with one infusion in these subjects.

CIDP
In the first CIDP study, a prospective multicenter open label trial PRIMA (Privigen impact on
mobility and autonomy study), 28 patients with CIDP (13 subjects with and 15 without IVIg
pre-treatment) were treated with a loading dose of 2 g/kg bw given over 2-5 days followed by
6 maintenance doses of 1 g/kg bw given over 1-2 days every 3 weeks. Previously treated
patients were withdrawn from IVIg before treatment with Privigen until the deterioration of
clinical symptoms was confirmed on the basis of the INCAT scale (Inflammatory Neuropathy
Cause and Treatment). On the adjusted 10 point INCAT scale a clinically meaningful
improvement of at least 1-point from baseline to treatment week 25 was observed in 17 / 28
patients (60.7%, 95% confidence interval 42.41, 76.4). Nine patients responded already after
receiving the initial induction dose to the treatment at week 4 and 16 by week 10.
In a second clinical study, a prospective, multicenter randomized, placebo-controlled PATH
[Polyneuropathy and Treatment with Hizentra] study, 207 subjects with CIDP were treated with
Privigen in the prerandomization phase of the study. Subjects all with IVIg pretreatment of at least
8 weeks and an IVIg-dependence confirmed by clinically evident deterioration during an IVIg
withdrawal phase of up to 12 weeks, received a Privigen loading dose of 2 g/kg bw followed by up to
4 Privigen maintenance doses of 1 g/kg bw every 3 weeks for up to 13 weeks.
Following clinical deterioration during IVIg withdrawal, clinical improvement of CIDP was primarily
defined by a decrease of ≥ 1 point at the adjusted INCAT score. Additional measures of CIDP
improvement were an R-ODS increase of ≥ 4 points, a mean grip strength increase of ≥ 8 kPa, or an
MRC sum score increase of ≥ 3 points. Overall, 91 % of subjects (188 patients) showed improvement
in at least one of the criteria above by week 13.
By adjusted INCAT score, the responder rate by week 13 was 72.9 % (151 / 207 patients), with
149 patients responding already by week 10. A total of 43 of the 207 patients achieved a better CIDP
status as assessed by the adjusted INCAT score compared to their CIDP status at study entry.
The comparability of the response rates and mean adjusted INCAT scores for the IVIg pretreated
subjects in both PRIMA and PATH study are shown in the Figure 1 below.

Figure 1. Percentage of Responders (Adjusted INCAT Score)

IVIg: intravenous immunoglobulin; Ref Visit: reference visit
The mean improvement at the end of the treatment period compared to reference visit was 1.4 points
in the PRIMA (1.8 points in IVIg pretreated subjects) and 1.2 points in PATH study.
In PRIMA, the percentage of responders in the overall Medical Research Council (MRC) score
(defined as an increase by ≥ 3 points) was 85 % (87 % in the IVIg-untreated and 82 % in IVIgpretreated)
and 57 % in PATH. The overall median time to first MRC sum score response in PRIMA
was 6 weeks (6 weeks in the IVIg-untreated and 3 weeks in the IVIg-pretreated) and 9.3 weeks in
PATH. MRC sum score in PRIMA improved by 6.9 points (7.7 points for IVIg-untreated and
6.1 points for IVIg-pretreated) and by 3.6 points in PATH.
The grip strength of the dominant hand improved by 14.1 kPa (17.0 kPa in IVIg-untreated and
10.8 kPa in IVIg pretreated subjects) in the PRIMA study, while in PATH the grip strength of the
dominant hand improved by 12.2 kPa. For the non-dominant hand similar results were observed in
both studies, PRIMA and PATH.
The efficacy and safety profile in the PRIMA and the PATH study in CIDP patients were overall
comparable.
Paediatric population
No differences were seen in the pharmacodynamic properties between adult and paediatric
study patients.

Privigen is immediately and completely bioavailable in the recipient’s circulation after
intravenous administration. It is distributed relatively quickly between plasma and
extravascular fluid. Equilibrium between the intravascular and extravascular compartments is
reached after approximately 3 to 5 days.

IgG and IgG complexes are broken down in the cells of the reticuloendothelial system. The half-life
may vary from patient to patient.
The pharmacokinetic parameters for Privigen were determined in both clinical studies in
patients with primary immunodeficiency syndrome (see section “Properties/Effects”). 25
patients (aged 13 to 69 years) in the pivotal study and 13 patients (aged 9 to 59 years) in an
extension of this study participated in the pharmacokinetic (PK) assessment (see table below).

Pharmacokinetic parameters of Privigen in patients with primary immunodeficiency
syndrome

Cmax, maximum serum concentration; Cmin, trough (minimum level) serum concentration; t½, elimination half-life.

In the pivotal study the median half-life of Privigen in primary immunodeficiency patients
was 36.6 days and 31.1 days in the extension of this study.
Paediatric population
No differences were seen in the pharmacokinetic parameters between adult and paediatric
study patients with PID. There are no data on pharmacokinetic properties in paediatric
patients with CIDP.

The safety of Privigen has been investigated in several preclinical studies with particular
reference to the excipient L-proline. L-proline is a physiological, non-essential amino acid.
Studies in rats given daily L-proline doses of 1450 mg/kg bw did not show any evidence of
teratogenicity or embryotoxicity. Genotoxicity studies of L-proline did not show any
pathological findings.
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. Further safety-pharmacology studies of L-proline in adult and
juvenile rats did not reveal behavioural disorders.
Immunoglobulins are natural components of the human body. Data from animal testing of
acute and chronic toxicity and embryofoetal toxicity of immunoglobulins are inconclusive on
account of interactions between immunoglobulins from heterogeneous species and the
induction of antibodies to heterologous proteins. In local tolerability studies in rabbits in
which Privigen was administered intravenously, paravenously, intra-arterially, and
subcutaneously, the product was well tolerated.

L-proline, water for injections.
Privigen contains trace amounts of sodium (≤ 1 mmol/l).
Privigen contains no preservatives.
Privigen contains no carbohydrate stabiliser (e.g. sucrose, maltose).

Incompatibilities
This medicine must not be mixed with other medicinal products nor with physiological saline.
However, dilution with 5% glucose solution is permitted.

Store at 2 - 25 °C. Do not freeze. Do not use if Privigen has been frozen. Do not shake.
Keep out of the sight and reach of children.
Keep the vial in the outer carton in order to protect from light.

NA

Privigen is a ready-to-use solution. The product should be at room or body temperature before
use. A vented infusion line with integrated filter should be used for the administration of
Privigen. Always pierce the stopper at its centre, within the marked area.
If dilution is desired, 5% glucose solution should be used. For obtaining an immunoglobulin
solution of 50 mg/ml (5%), Privigen 100 mg/ml (10%) should be diluted with an equal
volume of the 5% glucose solution. Aseptic technique must be strictly observed during the
dilution of Privigen.
Privigen must not be mixed with physiological saline. However, after-rinsing of the infusion
tubes with physiological saline is permitted.
The solution must be clear or slightly opalescent. Do not use solutions that are cloudy or have
particulate matter.
Any unused product and waste material should be disposed of in accordance with local
requirements.