Hizentra

1

ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS



2

1. NAME OF THE MEDICINAL PRODUCT

Hizentra 200 mg/ml solution for subcutaneous injection
Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Human normal immunoglobulin (SCIg)

One ml contains:
Human normal immunoglobulin................................................................................................ 200 mg
(purity:  at least 98% is immunoglobulin type G (IgG))

Vials
Each vial of 5 ml solution contains: 1 g of human normal immunoglobulin
Each vial of 10 ml solution contains: 2 g of human normal immunoglobulin
Each vial of 20 ml solution contains: 4 g of human normal immunoglobulin
Each vial of 50 ml solution contains: 10 g of human normal immunoglobulin

Pre-filled syringes
Each pre-filled syringe of 5 ml solution contains: 1 g human normal immunoglobulin
Each pre-filled syringe of 10 ml solution contains: 2 g human normal immunoglobulin

Distribution of the IgG subclasses (approx. values):
IgG1 ...........69%
IgG2 ...........26%
IgG3 ...........3%
IgG4 ...........2%

The maximum IgA content is 50 micrograms/ml.

Produced from the plasma of human donors.

Excipients with known effects
Hizentra contains approximately 250 mmol/L (range: 210 to 290) of L-proline.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Solution for subcutaneous injection.
The solution is clear and pale-yellow or light-brown.
Hizentra has an approximate osmolality of 380 mOsmol/kg.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Replacement therapy in adults, children and adolescents (0-18 years) in:
 Primary immunodeficiency syndromes with impaired antibody production (see section 4.4).



3

 Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic 
lymphocytic leukaemia (CLL), in whom prophylactic antibiotics have failed or are contra-
indicated.

 Hypogammaglobulinaemia and recurrent infections in multiple myeloma (MM) patients.
 Hypogammaglobulinaemia in patients, pre- and post-allogeneic haematopoietic stem cell 

transplantation (HSCT).

Immunomodulatory therapy in adults, children and adolescents (0-18 years):
 Hizentra is indicated for the treatment of patients with chronic inflammatory demyelinating 

polyneuropathy (CIDP) as maintenance therapy after stabilization with IVIg.

4.2 Posology and method of administration

The dose and dose regimen are dependent on the indication.

Therapy should be initiated and monitored under the supervision of a healthcare professional 
experienced in the treatment of immunodeficiency/CIDP with SCIg.

Posology
Adults and children (0-18 years)

Replacement therapy
The medicinal product should be administered via the subcutaneous route.

In replacement therapy the dose may need to be individualised for each patient dependent on the 
clinical response and serum IgG trough levels. The following dose regimens are given as a guideline.

The dose regimen should achieve a trough level of IgG (measured before the next infusion) of at least 
5 to 6 g/l and aim to be within the reference interval of serum IgG for age. A loading dose of at least 
0.2 to 0.5 g/kg (1.0 to 2.5 ml/kg) body weight may be required. This may need to be divided over 
several days. After steady state IgG levels have been attained, maintenance doses are administered at 
repeated intervals to reach a cumulative monthly dose of the order of 0.4 to 0.8 g/kg (2.0 to 4.0 ml/kg) 
body weight. Each single dose may need to be injected at different anatomic sites.

Trough levels should be measured and assessed in conjunction with the patient’s clinical response. 
Depending on the clinical response (e.g. infection rate), adjustment of the dose and/or the dose interval 
may be considered in order to aim for higher trough levels.

Immunomodulatory therapy in CIDP
The therapy with Hizentra is initiated 1 week after the last IVIg infusion. The recommended 
subcutaneous dose is 0.2 to 0.4 g/kg body weight per week administered in 1 or 2 sessions over 1 or 2 
consecutive days. The initial subcutaneous dose may be a 1:1 conversion from the previous IVIG dose 
(calculated as weekly dose). 
Example a 1g/kg IVIG dose given every 3 weeks would convert into a 0.33g/kg weekly Hizentra dose.
The weekly dose can be divided into smaller doses and administered by desired number of times per 
week. For dosing every two weeks, double the weekly Hizentra dose.

The dose may need to be adapted to achieve the desired clinical response. Patient`s individual clinical 
response should be the primary consideration in dose adjustment. In case of clinical deterioration the 
dose may be increased to the recommended maximum of 0.4g/kg weekly dose.
Hizentra maintenance therapy in CIDP has not been studied for periods longer than 18 months. 
Individualize the duration of any treatment beyond 18 months based upon the patient’s response and 
demonstrated need for continued therapy.



4

Efficacy of Hizentra has been demonstrated over placebo after switching from intravenous 
immunoglobulins (IVIG). Direct comparative data for Hizentra versus IVIG are not available. Please 
refer also to section 5.1.

Paediatric population
The posology in children and adolescents (0-18 years) is not different to that of adults as the posology 
for each indication is given by body weight and adjusted to the clinical outcome in replacement 
therapy indications.

Hizentra was evaluated in 68 paediatric subjects with PID aged 2 to <12 years and in 57 adolescents
aged 12 to <18 years. No paediatric-specific dose requirements were necessary to achieve the desired 
serum IgG levels. Hizentra has not been evaluated in clinical studies in paediatric patients with CIDP 
who are under the age of 18.

Elderly population
As the dose is given by body weight and adjusted to the clinical outcome of the above mentioned 
conditions, the dose in the elderly population is not considered to be different from that in subjects 18 
to 65 years of age.
In clinical studies Hizentra was evaluated in 13 subjects with PID >65 years of age and no specific 
dose adjustments were necessary to achieve the desired serum IgG levels.
In clinical studies Hizentra was evaluated in 61 subjects with CIDP >65 years of age and no specific 
dose adjustments were necessary to achieve the desired clinical outcome.

Method of administration

For subcutaneous use only.

Home-treatment
Subcutaneous infusion for home treatment must be initiated and monitored by a healthcare 
professional experienced in the guidance of patients for home treatment. Infusion devices appropriate 
for subcutaneous administration of immunoglobulins can be used. The patient or a caregiver must be 
instructed in the use of infusion devices, the keeping of treatment diary, recognition of and measures 
to be taken in case of severe adverse reactions.

Hizentra may be infused into sites such as abdomen, thigh, upper arm, and / or lateral hip.
More than one infusion device can be used simultaneously. The amount of product infused into a 
particular site may vary. In infants and children, infusion site may be changed every 5-15 ml. In adults 
doses may be given up to 50 ml/site. There is no limit to the number of infusion sites. Infusion sites 
should be at least 5 cm apart.

Infusion rate
Hizentra can be infused using:

 an infusion device, or

 by manual push with a syringe.

The recommended initial infusion rate depends on the individual patient’s needs.

Device-assisted infusion
The initial infusion rate should not exceed 20 ml/hour/site.
If well-tolerated (see also section 4.4), the infusion rate can then gradually be increased to 
35 ml/hour/site for the subsequent two infusions. Thereafter, if the patient tolerates the initial infusions 
at the full dose per site and maximum rate, an increase in the infusion rate of successive infusions may 
be considered at the discretion of the patient and based on the healthcare professionals’ judgement.

Manual push infusion



5

The recommended initial infusion rate should not exceed 0.5 ml/min/site (30 ml/hour/site).
If well-tolerated (see also section 4.4), the infusion rate can be increased up to 2.0 ml/min/site
(120 ml/hour/site). Thereafter, if the patient tolerates the initial infusions at the full dose per site and 
maximum rate, an increase in the infusion rate of successive infusions may be considered at the 
discretion of the patient and based on the healthcare professionals’ judgement.

A 24 or larger (i.e. lower gauge number) needle gauge may be required to allow patients to infuse at 
higher flow rates. Using smaller needles (i.e. higher gauge number) may make it more difficult to 
manually push Hizentra. Only one infusion site per syringe can be infused. If administration with an 
additional Hizentra syringe is required, a new sterile injection needle should be used and the infusion 
site changed.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 (see section 
4.4).
Patients with hyperprolinaemia type I or II.
Hizentra must not be given intravascularly.

4.4 Special warnings and precautions for use

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.

Hizentra is for subcutaneous use only. If Hizentra is accidentally administered into a blood vessel, 
patients could develop shock.

The recommended infusion rate given under section 4.2 should be adhered to. Patients should be 
closely monitored and carefully observed for any adverse events throughout the infusion period.

Certain adverse reactions may occur more frequently 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 treatment has been stopped for more than eight weeks.

Potential complications can often be avoided by ensuring that patients:
 are not sensitive to human normal immunoglobulin, by initially injecting the product slowly 

(see section 4.2);
 are carefully monitored for any symptoms throughout the infusion period. In particular, patients 

naïve to human normal immunoglobulin, patients switched from an alternative 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 
reactions.

All other patients should be observed for at least 20 minutes after administration.

Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the 
injection. In case of shock, standard medical treatment should be administered.

Hypersensitivity
True allergic reactions are rare. They can particularly occur in patients with anti-IgA antibodies who 
should be treated with particular caution. Patients with anti-IgA antibodies, in whom treatment with 
subcutaneous IgG products remains the only option, should be switched to Hizentra only under close 
medical supervision.
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.



6

Thromboembolism
Arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous 
thrombosis and pulmonary embolism have been associated with the use of immunoglobulins. Caution 
should be exercised 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 immobilization, 
severely hypovolemic patients, patients with diseases which increase blood viscosity). Patients should 
be informed about first symptoms of thromboembolic events including shortness of breath, pain and 
swelling of a limb, focal neurological deficits and chest pain and should be advised to contact their 
physician immediately upon onset of symptoms. Patients should be sufficiently hydrated before use of 
immunoglobulins.

Aseptic Meningitis Syndrome (AMS)

AMS has been reported with use of IVIg or SCIg. The syndrome usually begins within several hours 

to 2 days following immune globulin treatment. AMS is characterised by the following signs and 

symptoms: severe headache, neck stiffness, drowsiness, fever, photophobia, nausea, and vomiting. 

Patients exhibiting signs and symptoms of AMS should receive a thorough neurological examination, 

including CSF studies, to rule out other causes of meningitis. Discontinuation of immunoglobulin 

treatment may result in remission of AMS within several days without sequelae.

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 
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 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.

Interference with serological testing
After infusion 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 (Coombs’ test).

Sodium content
Hizentra is essentially sodium free.

Paediatric population
The same warnings and precautions apply to the paediatric population.

Elderly population
The same warnings and precautions apply to the elderly population.

4.5 Interactions with other medicinal products and other forms of interaction

Live attenuated virus vaccines



7

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.

Paediatric population
The same interactions may occur in the paediatric population.

Elderly population
The same interactions may occur in the elderly population.

4.6 Fertility, pregnancy and lactation

Pregnancy
Data from prospective clinical trials on the use of human normal immunoglobulin in pregnant women 
is limited. Therefore, Hizentra should only be given with caution to pregnant women. Clinical 
experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on 
the foetus or the neonate are to be expected.
Continued treatment of the pregnant woman ensures a passive immunity for the neonate.

Breast-feeding
Data from prospective clinical trials on the use of human normal immunoglobulin in breast feeding
women is limited. Therefore, Hizentra should only be given with caution to breast-feeding mothers.
Clinical experience with immunoglobulins suggests however that no harmful effects on the neonate 
are to be expected. Immunoglobulins are excreted into the milk and may contribute to the transfer of 
protective antibodies to the neonate.

Fertility
Clinical experience with immunoglobulins suggests that no harmful effects on fertility are to be 
expected.

4.7 Effects on ability to drive and use machines

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

4.8 Undesirable effects

Summary of safety profile
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.

Local reactions at infusion sites: swelling, soreness, redness, induration, local heat, itching, bruising 
and rash.

For safety with respect to transmissible agents, see section 4.4.

Tabulated list of adverse reactions
Adverse Reactions (ARs) have been collected in Hizentra clinical trials from 7 phase III studies in 
patients with primary immunodeficiency (n = 231), 2 phase IV studies in patients with PID (n=74), 1



8

phase III study (n = 115), and 1 extension study (n = 82) in patients with CIDP (total N = 502 patients; 
26,646 infusions). The ADRs reported in these clinical studies are summarised and categorised 
according to the MedDRA System Organ Class (SOC and Preferred Term level) and frequency below.

Frequency per patient or 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), Rare (≥1/10,000 to <1/1,000), 
Very rare (<1/10,000). For spontaneous post-marketing ADRs, the reporting frequency is categorised 
as unknown.

Frequency of Adverse Drug Reactions (ADR) associated with Hizentra obtained from clinical 
studies and post-marketing surveillance, reporting rate per patient or per infusion

System Organ 
Class
(SOC, MedDRA)

ADRs (MedDRA Preferred Term, PT) ADR frequency 
category per patient

ADR frequency 
category per 

infusion
Immune system 
disorders

Hypersensitivity Uncommon Rare
Anaphylactic reaction Unknown Unknown

Nervous system 
disorders

Headache Very common Uncommon
Dizziness, Migraine Common Rare
Tremor (including Psychomotor 
hyperactivity)

Uncommon Rare

Meningitis aseptic Uncommon Very rare
Burning sensation Unknown Unknown

Cardiac disorders Tachycardia Uncommon Very rare
Vascular disorders Hypertension Common Rare

Flushing Uncommon Rare
Embolic and thrombotic events Unknown Unknown

Gastrointestinal 
disorders

Diarrhoea, Abdominal pain Common Uncommon
Nausea, Vomiting Common Rare

Skin and 
subcutaneous 
tissue disorders

Rash Very common Uncommon
Pruritus, Urticaria Common Rare

Musculoskeletal 
and connective 
tissue disorders

Musculoskeletal pain, Arthralgia Common Uncommon

Muscle spasm, Muscular weakness Uncommon Rare
General disorders 
and administration 
site conditions

Infusion site reaction Very common Very common

Fatigue (including Malaise), Pyrexia Common Uncommon

Chest pain, Influenza like illness, Pain Common Rare

Chills (including Hypothermia) Uncommon Rare

Infusion site ulcer Unknown Unknown

Investigations Blood creatinine increased Uncommon Rare



9

Paediatric population
Clinical trials with Hizentra showed a similar overall safety profile in paediatric and adult patients 
with PID.
Hizentra was not evaluated in clinical studies in paediatric patients with CIDP who were under the age 
of 18.

Elderly population
The same adverse reactions may occur in the elderly population. Information available from clinical 
trials showed no difference in the safety profile of patients ≥ 65 years of age than of younger patients.
Postmarketing experience with Hizentra in patients ≥ 65 years of age shows an overall similar safety 
profile in this age group as in younger patients.
Please refer to section 4.4 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 via the national reporting 
system listed in Appendix V.

4.9 Overdose

Consequences of an overdose are not known.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: immune sera and immunoglobulins: immunoglobulins, normal human, 
for extravascular administration, ATC code: J06BA01.

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. 

Mechanism of action
In immunodeficiency, adequate doses of Hizentra may restore abnormally low immunoglobulin G 
antibody levels to the normal range and thus help against infections.
The mechanism of action in indications other than replacement therapy is not fully elucidated, but 
includes immunomodulatory effects.

PID
In the European pivotal prospective open label, single arm and multicentre study, a total of 51 subjects 
with primary immunodeficiency syndromes aged between 3 and 60 years old were treated with 
Hizentra for up to 41 weeks. The mean dose administered each week was 0.12 g/kg body weight (bw). 
Sustained IgG trough levels with mean concentrations of 7.99 – 8.25 g/l were thereby achieved 
throughout the treatment period. Subjects received in total 1,831 weekly Hizentra infusions.

In the US prospective open label, single arm and multicentre study, a total of 49 subjects with primary 
immunodeficiency syndromes aged between 5 and 72 years old were treated with Hizentra for up to 
15 months. The mean dose administered each week was 0.23 g/kg bw. Sustained IgG trough levels 
with a mean concentration of 12.53 g/l were thereby achieved throughout the treatment period. 
Subjects received in total 2,264 weekly Hizentra infusions.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


10

No serious bacterial infections were reported during the efficacy period in subjects receiving Hizentra 
during clinical studies.

To assess the safety and tolerability of higher infusion rates applied via the manual push and pump-
assisted administration, 49 PID subjects aged 2 to 75 years were enrolled in an open-label, multicentre, 
parallel-arm, nonrandomised phase IV HILO (Hizentra Label Optimization) study and treated with 
Hizentra for at least 12 weeks (11 paediatric patients aged 2 to <18, 35 adult patients aged 18 to 65, 
and 3 geriatric patients aged >65 years). In the first patient group receiving Hizentra via the manual 
push technique (n=16), 2 to 7 infusions per week were administered with the flow rates of 30, 60 and 
120 ml/hour/site (see section 4.2). In the second patient group receiving Hizentra via pump-assisted 
administration (n=18), weekly Hizentra infusions were administered with 25, 50, 75 and 100 
ml/hour/site flow rate. In a third group, infusion volumes of 25, 40 and 50ml per site were additionally 
evaluated in pump-assisted administration of weekly Hizentra doses (n=15). In all three groups, each 
infusion parameter was used for 4 weeks, after which subjects successfully completing required 
minimal number of valid infusions could switch to the next higher infusion parameter.
The primary endpoint was the percentage of subjects responding to a higher infusion parameter:

Group Infusion parameter and responder rate (%)
1. manual push

flow rates
30 ml/hour/site 60 ml/hour/site 120 

ml/hour/site
-

100.0 % 100.0 % 87.5 % -
2. pump-assisted

flow rates
25 ml/hour/site 50 ml/hour/site 75 ml/hour/site 100 ml/hour/site
77.8 % 77.8 % 66.7 % 61.1 %

3. pump-assisted
volumes

25 ml/site 40 ml/site 50 ml/site -
86.7 % 73.3 % 73.3 % -

Responder: in the pump-assisted group a subject who performed ≥3 valid infusions out of 4 for an infusion 
parameter; in the manual push group a subject who performed ≥60 % of valid infusions for an infusion 
parameter. An infusion was considered valid, if ≥95 % of the planned flow rate/volume per ≥1 infusion site 
was achieved.

Overall, the number of infusions without severe local reactions versus the total number of infusions
(tolerability) was ≥ 0.98 in all groups for all infusion parameters. No clinically relevant differences in 
the serum IgG trough concentrations were observed between the baseline at day 1 and the end of the 
study in all subjects.

CIDP
The safety, efficacy and tolerability of Hizentra in patients with CIDP has been assessed in a 
multicentre, double-blind, randomised, placebo-controlled, parallel-group phase III PATH 
[Polyneuropathy and Treatment with Hizentra] study. 172 adults with definite or probable CIDP who 
were previously treated with and responded to IVIg were randomised to weekly 0.2 g/kg bw Hizentra, 
weekly 0.4 g/kg bw Hizentra or placebo groups, and followed for a subsequent 24 weeks. The mean 
duration of exposure was 118.9 days in the 0.2 g/kg bw and 129 days in the 0.4 g/kg bw Hizentra 
group (maximum exposure up to 167 and 166 days in each group, respectively). Subjects generally 
used 4 infusion sites in parallel (up to 8 sites in parallel). In total, 57 subjects received 1514 infusions 
in the placebo group, 57 subjects received 2007 infusions in the 0.2 g/kg bw Hizentra group, and 58 
subjects received 2218 infusions in the 0.4 g/kg bw Hizentra group (in total 5739 infusions).

The primary efficacy endpoint was the percentage of subjects who had a CIDP relapse (defined as a ≥ 
1 point increase in adjusted Inflammatory Neuropathy Cause and Treatment [INCAT] score compared 
with baseline) or were withdrawn for any other reason in the Hizentra treatment period.
Both Hizentra doses demonstrated superiority over placebo for the primary endpoint. A statistically 
significant lower percentage of subjects treated with Hizentra, 32.8 % for 0.4 g/kg bw and 38.6 % for 
0.2 g/kg bw, had CIDP relapse or was withdrawn for other reasons compared with 63.2 % subjects 
treated with placebo (p < 0.001 or p = 0.007, respectively). When only considering relapse, the CIDP 
relapse rates were 19.0 % for 0.4 g/kg bw Hizentra and 33.3 % for 0.2 g/kg bw Hizentra compared 
with 56.1 % for placebo (p < 0.001 or p = 0.012, respectively). Accordingly, over the treatment period 



11

for up to 24 weeks Hizentra prevented relapse in 81 % and 67 % of subjects in the 0.4 g/kg bw and 0.2 
g/kg bw group, respectively, while in the placebo group 44 % of subjects remained relapse-free.

Time to CIDP relapse (Figure 1) was evaluated, and the corresponding probabilities for CIDP relapse 
based on Kaplan-Meier estimates were: placebo, 58.8 %; 0.2 /kg bw Hizentra, 35.0 %; and 0.4 g/kg 
bw Hizentra, 22.4 %. The hazard ratios (95 % CI) for the lower dose and higher dose compared to 
placebo was 0.48 (0.27, 0.85) and 0.25 (0.12, 0.49), respectively.
The difference observed between the 0.2 g/kg bw and the 0.4 g/kg bw Hizentra groups did not reach 
statistical significance.

Figure 1. Kaplan-Meier Plot Time to CIDP Relapse

In the efficacy scores (INCAT score, mean grip strength, and Medical Research Council sum score), 
subjects in both Hizentra dose groups remained stable while subjects in the placebo group 
deteriorated. Subjects in the high dose Hizentra group remained stable in the Rasch-built Overall 
Disability Scale (R-ODS) centile score. Subjects in both Hizentra dose groups remained stable in 
electrophysiology parameters.

A phase III, multicentre, 48-week open-label extension study enrolled 82 CIDP patients from the 
PATH study. The extension study investigated the long-term safety and efficacy of Hizentra 
maintenance therapy in the two weekly doses, 0.2 g/kg and 0.4 g/kg bw. Due to the study design, the 
same subject could receive both doses during the study; 72 subjects received doses of 0.4 g/kg and 73 
subjects received doses of 0.2 g/kg during the efficacy evaluation period. The mean efficacy 
evaluation period was 125.8 days (range: 1-330) in the 0.2 g/kg, and 196.1 days (range: 1-330) in the 
0.4 g/kg bw group. Patients who completed the pivotal PATH study without relapse on 0.4 g/kg bw 
dose and initially received this dose in the extension study had a relapse rate of 5.6 % (1/18 patients). 
For all patients who received 0.4 g/kg bw in the PATH extension study, 9.7 % (7/72 patients) had a 
relapse. Patients who completed the PATH study without relapse on 0.2 g/kg bw dose and initially 
received this dose in the extension study had a relapse rate of 50 % (3/6 patients). For all patients who 
received 0.2 g/kg bw in the extension study, 47.9 % (35/73 patients) had a relapse. Down-titrating 



12

patients in the extension study who completed the PATH study on either dose from 0.4 g/kg to 0.2 
g/kg bw dose was possible in 67.9 % of subjects (19/28 patients) without occurrence of relapse; all of 
the 9 relapsers recovered within 4 weeks after treatment with 0.4 g/kg bw dose. Grip strength, MRC 
sum score, and R-ODS centile score remained stable as compared to baseline for patients who never 
had a relapse in the extension study.

Paediatric population
The safety and effectiveness of Hizentra have been established in paediatric subjects 2 to 18 years of 
age. Hizentra was evaluated in 68 paediatric subjects with PID 2 to <12 years of age and in 57 
paediatric subjects 12 to <18 years of age. There were no differences in the pharmacokinetics, safety 
and efficacy profiles as compared with adult subjects. No paediatric-specific dose adjustments were 
necessary to achieve the desired serum IgG levels. No differences were seen in the pharmacodynamic 
properties between adult and paediatric study patients with PID. 
Hizentra has not been evaluated in clinical studies in paediatric patients with CIDP who are under the 
age of 18.

Elderly population
No overall differences in safety or efficacy were observed between PID subjects >65 years and PID 
subjects 18 to 65 years of age. In the clinical studies Hizentra was evaluated in 13 patients with PID 
>65 years of age.
No overall differences in safety or efficacy were observed between CIDP subjects >65 years and CIDP 
subjects 18 to 65 years of age. In the clinical studies with CIDP patients, 61 subjects >65 years of age 
were treated with Hizentra.

5.2 Pharmacokinetic properties

Absorption and Distribution
Following subcutaneous administration of Hizentra, peak serum levels are achieved after 
approximately 2 days.

Elimination
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.

PID
In a clinical phase III trial with Hizentra (n = 46), the subjects achieved sustained trough levels 
(median 8.1 g/l) over a period of 29 weeks when receiving median weekly doses of 0.06 to 
0.24 g/kgbw.

Simulations by empirical Population Pharmacokinetic models suggested that comparable IgG 
exposure levels (AUC0-14days, Cmin 14days) may be obtained if Hizentra is administered subcutaneously 
every two weeks using double the weekly dose during maintenance therapy.
These simulations further suggested that comparable serum IgG trough levels can be achieved when 
the weekly maintenance dose of Hizentra is administered in proportional amounts more frequently 
than once a week (e.g. 2 times per week, 3 times per week, 5 times per week or daily).

Simulation of 2-3 missed daily doses resulted in a median serum IgG level decrease of ≤ 4% compared 
to consistent daily dosing. By replacing the missed doses when daily dosing was resumed, the median 
concentration profile recovered within 2 to 3 days. However, if missed doses were not replaced when 
dosing was resumed, it took up to 5-6 weeks for the IgG trough levels to return to steady-state.

Paediatric population
No differences were seen in the pharmacokinetic parameters between adult and paediatric PID study 
patients.



13

Elderly population
No overall differences in the pharmacokinetic parameters were observed between PID subjects >65 
years and subjects 18 to 65 years of age.

CIDP
In the PATH study, subjects (n = 172) achieved sustained trough levels over a period of 24 weeks 
when receiving weekly doses of 0.2 g/kg bw and 0.4 g/kg bw, respectively. The mean (SD) IgG trough 
concentration after Hizentra treatment in the 0.4 g/kg bw group was 20.4 (3.24) g/l and 15.4 (3.06) g/l 
in the 0.2 g/kg bw group. Simulations with population-pharmacokinetic models in the PATH study 
suggest that a comparable IgG exposure (Cmax, AUC0-14days, Cmin, 14 days) is achieved when the 
double weekly Hizentra dose is administered every two weeks in the CIDP subjects. These simulations 
further suggest that a comparable IgG exposure is correspondingly achieved when the weekly 
maintenance dose of Hizentra is divided in several, more frequent doses (2 to 7 times per week) in the 
CIDP patients` population.

Paediatric population
Hizentra has not been evaluated in clinical studies in paediatric patients with CIDP who are under the 
age of 18.

Elderly population
No overall differences in the pharmacokinetic parameters were observed between CIDP subjects >65 
years and subjects 18 to 65 years of age.

5.3 Preclinical safety data

Immunoglobulins are a normal constituent of the human body. L-proline is a physiological, non-
essential amino acid.

The safety of Hizentra has been assessed in several preclinical studies, with particular reference to the 
excipient L-proline. 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
Polysorbate 80
Water for injections

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products.

6.3 Shelf life

30 months
Once a vial or the blistered pre-filled syringe has been opened, the solution should be used 
immediately.

6.4 Special precautions for storage

Do not store above 25 °C.
Do not freeze.



14

Keep the vial or the blistered pre-filled syringe in the outer carton in order to protect from light.

For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

Vials
5, 10 or 20 ml of solution in a vial (type I glass) and 50 ml of solution in a vial (type II glass), with a 
stopper (halobutyl), a cap (aluminium crimp) and a flip off disc (plastic).

Pack sizes of 1, 10 or 20 vials:
  1 g / 5 ml
  2 g / 10 ml
  4 g / 20 ml
10 g / 50 ml

Pre-filled syringes
5, or 10 ml of solution in a pre-filled syringe (cyclo-olefin-copolymer (COC)).

Pack sizes of 1 or 10 pre-filled syringes:
  1 g / 5 ml
  2 g / 10 ml

Alcohol swabs, needles and other supplies or equipment are not contained in the pack.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Hizentra comes as a ready-to-use solution in single-use vials or single-use pre-filled syringes. Because 
the solution contains no preservative, Hizentra should be used/infused as soon as possible after 
opening the vial or blistered pre-filled syringe.

The medicinal product should be brought to room or body temperature before use.

The solution should be clear and pale-yellow or light-brown.
Solutions that are cloudy or have deposits should not be used.

Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.

7. MARKETING AUTHORISATION HOLDER

CSL Behring GmbH
Emil-von-Behring-Strasse 76
D-35041 Marburg
Germany

8. MARKETING AUTHORISATION NUMBERS

Vials
EU/1/11/687/001
EU/1/11/687/002
EU/1/11/687/003



15

EU/1/11/687/004
EU/1/11/687/005
EU/1/11/687/006
EU/1/11/687/010
EU/1/11/687/011
EU/1/11/687/012
EU/1/11/687/013
EU/1/11/687/014

Pre-filled syringes
EU/1/11/687/015
EU/1/11/687/016
EU/1/11/687/017
EU/1/11/687/018

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 14 April 2011
Date of first renewal: 18 February 2016

10. DATE OF REVISION OF THE TEXT

Detailed information on this medicinal product is available on the website of the European Medicines 
Agency: http://www.ema.europa.eu.



16

ANNEX II

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

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT



17

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

Name and address of the manufacturer of the biological active substance

CSL Behring AG
Wankdorfstrasse 10
CH-3000 Bern 22
Switzerland

Name and address of the manufacturer 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 OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

 Official batch release

In accordance with Article 114 of Directive 2001/83/EC, the official batch release will be undertaken 
by a state laboratory or a laboratory designated for that purpose.

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic safety update reports (PSURs)

The requirements for submission of PSURs for this medicinal product are set out in the list of Union 
reference dates (EURD list) provided for under Article 107c(7) of Directive 2001/83/EC and any 
subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk management plan (RMP)

The marketing authorisation holder (MAH) shall perform the required pharmacovigilance activities 
and interventions detailed in the agreed RMP presented in Module 1.8.2 of the marketing authorisation 
and any agreed subsequent updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result
of an important (pharmacovigilance or risk minimisation) milestone being reached.



18

If the submission of a PSUR and the update of a RMP coincide, they can be submitted at the same 
time.



19

ANNEX III

LABELLING AND PACKAGE LEAFLET



20

A. LABELLING



21

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER BOX (vial)

1. NAME OF THE MEDICINAL PRODUCT

Hizentra 200 mg/ml solution for subcutaneous injection
human normal immunoglobulin (SCIg)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 ml contains:
Human normal immunoglobulin 200 mg
IgG .......................................... ≥ 98%
IgA .......................... ≤ 50 micrograms

  1 g/5 ml
  2 g/10 ml
  4 g/20 ml
10 g/50 ml

3. LIST OF EXCIPIENTS

Excipients: L-proline, polysorbate 80, water for injections.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection

1 x 5 ml
1 x 10 ml
1 x 20 ml
1 x 50 ml
10 x 5 ml
10 x 10 ml
10 x 20 ml
10 x 50 ml
20 x 5 ml
20 x 10 ml
20 x 20 ml

Vial(s)

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For subcutaneous use only.



22

Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

Do not inject intravascularly.

8. EXPIRY DATE

EXP

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)

EU/1/11/687/001 1 x 5 ml vial
EU/1/11/687/002 10 x 5 ml vials
EU/1/11/687/003 20 x 5 ml vials
EU/1/11/687/004 1 x 10 ml vial
EU/1/11/687/005 10 x 10 ml vials
EU/1/11/687/006 20 x 10 ml vials
EU/1/11/687/010 1 x 20 ml vial
EU/1/11/687/011 10 x 20 ml vials
EU/1/11/687/012 20 x 20 ml vials
EU/1/11/687/013 1 x 50 ml vial
EU/1/11/687/014 10 x 50 ml vials



23

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Hizentra

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



24

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

OUTER BOX (pre-filled syringe)

1. NAME OF THE MEDICINAL PRODUCT

Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe
human normal immunoglobulin (SCIg)

2. STATEMENT OF ACTIVE SUBSTANCE(S)

1 ml contains:
Human normal immunoglobulin 200 mg
IgG .......................................... ≥ 98%
IgA .......................... ≤ 50 micrograms

  1 g/5 ml
  2 g/10 ml

3. LIST OF EXCIPIENTS

Excipients: L-proline, polysorbate 80, water for injections.
See leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

Solution for injection

1 x 5 ml
1 x 10 ml
10 x 5 ml
10 x 10 ml

Pre-filled syringe(s)

5. METHOD AND ROUTE(S) OF ADMINISTRATION

For subcutaneous use only.
Read the package leaflet before use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY



25

Do not inject intravascularly.

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

Do not store above 25 °C.
Do not freeze.
Keep the blistered pre-filled syringe 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)

EU/1/11/687/015 1 x 5 ml pre-filled syringe
EU/1/11/687/016 10 x 5 ml pre-filled syringes
EU/1/11/687/017 1 x 10 ml pre-filled syringe
EU/1/11/687/018 10 x 10 ml pre-filled syringes

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Hizentra



26

17. UNIQUE IDENTIFIER – 2D BARCODE

2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA

PC:
SN:
NN:



27

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

VIAL

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Hizentra 200 mg/ml solution for subcutaneous injection
human normal immunoglobulin (SCIg)
For subcutaneous use only.

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 g/5 ml
2 g/10 ml
4 g/20 ml
10 g/50 ml

6. OTHER



28

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS

PRE-FILLED SYRINGE

1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION

Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe
human normal immunoglobulin (SCIg)
For subcutaneous use only.

2. METHOD OF ADMINISTRATION

3. EXPIRY DATE

EXP

4. BATCH NUMBER

Lot

5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT

1 g/5 ml
2 g/10 ml

6. OTHER



29

B. PACKAGE LEAFLET



30

Package leaflet: Information for the user

Hizentra 200 mg/ml solution for subcutaneous injection
Human normal immunoglobulin (SCIg = Subcutaneous Immunoglobulin)

Read all of this leaflet carefully before you start using this medicine, because it contains 
important information for you.

 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor or healthcare professional.
 This medicine has been prescribed for you only. Do not pass it on to others.

It may harm them, even if their signs of illness are the same as yours.
 If you get any side effects talk to your healthcare professional. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What Hizentra is and what it is used for
2. What you need to know before you use Hizentra
3. How to use Hizentra
4. Possible side effects
5. How to store Hizentra
6. Contents of the pack and other information

1. What Hizentra is and what it is used for

What Hizentra is
Hizentra belongs to the class of medicines called human normal immunoglobulins. Immunoglobulins 
are also known as antibodies and are blood proteins that help your body to fight infections.

How Hizentra works
Hizentra contains immunoglobulins that have been prepared from the blood of healthy people. 
Immunoglobulins are produced by human body’s immune system. They help your body to fight 
infections caused by bacteria and viruses or maintain the balance in your immune system (referred to 
as immunomodulation). The medicine works in exactly the same way as the immunoglobulins 
naturally present in your blood.

What Hizentra is used for
Replacement therapy
Hizentra is used to raise abnormally low immunoglobulin levels in your blood to normal levels
(replacement therapy). The medicine is used in adults and children (0-18 years) in the following
situations:

1. Treatment of patients who are born with a reduced ability or inability to produce 
immunoglobulins (primary immunodeficiencies). This includes conditions such as:
 low immunoglobulin levels (hypogammaglobulinaemia) or absence of immunoglobulins 

(agammaglobulinaemia) in the blood
 combination of low immunoglobulin levels, frequent infections and inability to produce 

adequate amounts of antibodies after vaccination (common variable immunodeficiency)
 combination of low level or absence of immunoglobulins and absence or non-functional 

immune cells (severe combined immunodeficiency)
 lack of certain immunoglobulin G subclasses causing recurrent infections.

2. Treatment of low immunoglobulin levels and recurrent bacterial infections in patients with
chronic lymphocytic leukaemia (CLL), a certain kind of blood cancer, where prophylactic 
antibiotics have failed or are contra-indicated.



31

3. Treatment of low immunoglobulin levels and recurrent bacterial infections in patients with 
multiple myeloma (MM), another kind of blood cancer.

4. Treatment of low immunoglobulin levels in patients pre- and post- allogeneic haematopoietic 
stem cell transplantation (HSCT).

Immunomodulatory therapy in CIDP patients
Hizentra is also used in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), a 
form of autoimmune disease. CIDP is characterised by chronic inflammation of the peripheral nerves 
that causes muscle weakness and/or numbness mainly in the legs and arms. It is believed that the 
body’s defense attack underlines such inflammation, and the immunoglobulins present in Hizentra 
help to protect the nerves from being attacked (immunomodulatory therapy).

2. What you need to know before you use Hizentra

Do NOT infuse Hizentra
► if you are allergic to human immunoglobulins, polysorbate 80 or L-proline.

 Tell your doctor or healthcare professional prior to treatment if you have experienced an
intolerance against one of these components earlier.

► if you suffer from hyperprolinaemia (a genetic disorder causing high levels of the amino acid 
proline in the blood).

► into a blood vessel.

Warnings and precautions
 Talk to your doctor or healthcare professional before using Hizentra.

You may be allergic (hypersensitive) to immunoglobulins without knowing it. However, true allergic 
reactions are rare. They may occur even if you received human immunoglobulins previously and 
tolerated them well. It may happen particularly if you do not have enough of the immunoglobulin type
A (IgA) in your blood (IgA deficiency).
 Tell your doctor or healthcare professional prior to treatment if you have an immunoglobulin 

type A (IgA) deficiency. Hizentra contains residual amounts of IgA which might cause an
allergic reaction.

In these rare cases allergic reactions, such as a sudden fall in blood pressure or shock may occur (see 
also section 4 “Possible side effects”).
 If you notice such signs during the infusion of Hizentra, stop the infusion and contact your 

doctor or go to the nearest hospital immediately. 

 Tell your doctor if you have a history of heart or blood vessel disease or blood clots, have thick 
blood, or have been immobile for some time. These things may increase your risk of having a blood 
clot after using Hizentra. Also tell your doctor what drugs you are using, as some drugs, such as those 
that contain the hormone estrogen (for example, birth control pills), may increase your risk of 
developing a blood clot. Contact your doctor immediately if you experience signs and symptoms such 
as shortness of breath, chest pain, pain and swelling of a limb, weakness or numbness on one side of 
the body after receiving Hizentra.

 Contact your doctor if you experience the following signs and symptoms: severe headache, neck 
stiffness, drowsiness, fever, photophobia, nausea, and vomiting after receiving Hizentra. Your doctor 
will decide if further tests are necessary and whether Hizentra should be continued.

Your healthcare professional will avoid potential complications by ensuring:
► that you are not sensitive to human normal immunoglobulin.

The medicine must be infused slowly at first. The recommended infusion rate given under 
section 3 “How to use Hizentra” must be closely followed.



32

► that you are carefully monitored for any symptoms throughout the infusion period, especially if:
 you receive human normal immunoglobulin for the first time
 you have switched from a different medicine
 there has been a long interval (more than eight weeks) since the previous infusion.
In these cases, it is recommended that you are monitored during the first infusion and for an 
hour afterwards. If the points above do not apply for you it is recommended that you are 
observed for at least 20 minutes after administration.

Other medicines and Hizentra
 Tell your doctor or healthcare professional if you are using, have recently used or might use any 

other medicines.
 You must not mix other medicines with Hizentra.
 Tell your vaccinating doctor prior to a vaccination about your treatment with Hizentra.

Hizentra may impair the effect of some live virus vaccines such as measles, rubella, mumps and 
chicken pox. Therefore, after receiving this medicine you may have to wait up to 3 months 
before receiving your live-attenuated vaccine. In the case of measles vaccinations the 
impairment may persist for up to 1 year.

Pregnancy, breast-feeding and fertility
 Tell your doctor or healthcare professional if you are pregnant, plan to become pregnant or are 

breast-feeding. Your doctor will decide whether you can receive Hizentra during your 
pregnancy or while you are breast-feeding.

No clinical studies have been performed with Hizentra in pregnant women. However, medicines that 
contain immunoglobulins have been used in pregnant or breast-feeding women for years, and no 
harmful effects on the course of pregnancy or on the baby have been observed.

If you are breast-feeding and receive Hizentra, the immunoglobulins of the medicine can also be found
in the breast milk. Therefore, your baby may be protected from certain infections.

Driving and using machines
Patients may experience effects, such as dizziness or nausea, during treatment with Hizentra that might 
affect the ability to drive and use machines. If this happens, you should not drive or use machines until 
these effects have disappeared.

Hizentra contains proline
You must not take it if you suffer from hyperprolinaemia (see also section 2 “What you need to know 
before you use Hizentra”). Please tell your doctor prior to treatment.

Other important information about Hizentra
Blood tests
After receiving Hizentra, the results of certain blood tests (serological tests) may be impaired for a 
certain time.
 Tell your doctor about your treatment with Hizentra prior to any blood test.

Information on what Hizentra is made of
Hizentra 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 medicines also include steps in the processing of the blood or plasma that can 
inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or 
plasma are administered, the possibility of passing on infection cannot be totally excluded. This also 
applies to any unknown or emerging viruses or other types of infections.



33

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

 It is strongly recommended that every time you receive a dose of Hizentra the name and batch 
number of the product are recorded in order to maintain a record of the batches used (see section 
3 “How to use Hizentra”).

3. How to use Hizentra

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure.

Dosage
Your doctor will calculate the correct dose for you taking into account your weight and response to 
treatment.
The dose or dosing interval should not be changed without consulting your doctor.
If you think you should receive Hizentra more or less frequently, please speak to your doctor.
If you think you have missed a dose, speak to your doctor as soon as possible.

Replacement therapy
Your doctor will determine whether you need a loading dose (for adults and children) of at least 1 to 
2.5 ml/kg of body weight divided over several days. Following this, maintenance doses may be given
at repeated intervals, from daily to once every two weeks, to reach a cumulative monthly dose of about 
2 to 4 ml/kg of body weight. Your healthcare professional may adjust the dose based on your response 
to the treatment.

Immunomodulatory therapy
Your doctor will initiate therapy with Hizentra 1 week after your last intravenous immunoglobulin 
infusion by administrating under the skin (subcutaneously) with a weekly dose of 1.0 to 2.0 ml/kg of 
body weight. Your doctor will determine your weekly Hizentra dose. The weekly maintenance doses 
may be divided into smaller doses and administered as often as required during the week. For dosing 
every two weeks, your doctor will double the weekly Hizentra dose. Your healthcare professional may 
adjust the dose based on your response to the treatment.

Method and route of administration
In case of home treatment, this will be initiated by a healthcare professional experienced in the 
treatment of immunodeficiency/CIDP with SCIg and in the guidance of patients for home treatment.

You will be instructed in:
 aseptic infusion techniques
 the keeping of a treatment diary, and
 measures to be taken in case of severe side effects.

Infusion site(s)
 Administer Hizentra under the skin only.
 You may infuse Hizentra into sites such as abdomen, thigh, upper arm, and lateral hip. If large 

doses are given (> 50 ml), try to administer them at multiple sites.
 You may use an unlimited number of sites simultaneously. Injection sites should be at least 

5 cm apart.
 In the case, you will use a device-assisted infusion technique (e.g. pump-assisted infusion), 

more than one infusion device can be used simultaneously.



34

 In the case, you will use the manual push infusion technique with a syringe, you may use only 
one infusion site per syringe. If you need to administer an additional Hizentra syringe, you must 
use a new sterile injection needle and change the infusion site.

 The volume of product infused into a particular site may vary.

Infusion rate(s)
Your doctor will determine the appropriate infusion technique and the infusion rate for you taking into 
account your individual dose, dosing frequency and product tolerability.

Device-assisted infusion:
The recommended initial infusion rate is up to 20 ml/hour/site. If well-tolerated, you may gradually 
increase the infusion rate to 35 ml/hour/site for the subsequent two infusions. Thereafter, the infusion 
rate can be increased further as per your tolerability.

Manual push infusion:
The recommended initial infusion rate is up to 0.5 ml/min/site (30 ml/hour/site). If well-tolerated, you 
may increase the infusion rate up to 2.0 ml/min/site (120 ml/hour/site) for subsequent infusions.
Thereafter, the infusion rate can be increased further as per your tolerability.

Instructions for use

Follow the steps below and use aseptic technique to administer Hizentra.
1 Clean surface

Thoroughly clean a table or other flat surface using an antiseptic wipe.
2 Assemble supplies

Place Hizentra and other supplies and equipment needed for the infusion on a clean, flat surface.
3 Thoroughly wash and dry hands
4 Check Vials

Visually inspect Hizentra for particles in the solution or discoloration as well as expiry date before 
administering Hizentra. Do not use solutions that are cloudy or contain particles. Do not use 
solutions that have been frozen. Administer solution which is at room or body temperature.
Once a vial has been opened, use the solution immediately.

5 Preparation of Hizentra for infusion

Clean the vial stopper – Remove the protective cap from the vial 
to expose the central portion of the rubber stopper. Clean the 
stopper with an alcohol wipe or antiseptic preparation and allow it 
to dry.

Transfer Hizentra to syringe for infusion – Attach a transfer 
device or needle to a sterile syringe, using aseptic technique. If 
using a transfer device (vented spike), follow the instructions 
provided by the device manufacturer. If using a needle, pull back 
on the plunger to draw air into the syringe that is comparable to 
the amount of Hizentra to be withdrawn. Then, insert the needle 
into the center of the vial stopper and, to avoid foaming, inject air 
into headspace of the vial (not into the liquid). Finally, withdraw 
the desired volume of Hizentra. When using multiple vials to 
achieve the desired dose, repeat this step.

6 Prepare the tubing
Attach the administration tubing or needle set to the syringe. Prime the tubing to eliminate all 
remaining air.



35

7 Prepare infusion site(s)
Select the infusion site(s) – The number and location of infusion
sites depends on the volume of the total dose. Each infusion site 
should be at least 5 cm apart.
You may use an unlimited number of sites simultaneously.

Clean the infusion site(s) using an antiseptic skin preparation, 
Allow each site to dry before proceeding.

8 Insert the needle
Grasp the skin between 2 fingers and insert the needle into the 
subcutaneous tissue.

Secure the needle to the skin – If necessary, use gauze and tape or 
transparent dressing to hold the needle in place.

9 Infuse Hizentra
Start infusion.
If using an infusion pump, follow the manufacturer’s instructions.

10 Record the infusion
Record the following data in your treatment diary:
• the date of administration,
• the batch number of the medicine, and
• the infused volume, flow rate, the number and location of infusion sites.

11 Clean up
Discard any unused product and all used administration supplies after administration in accordance 
with local requirements.

If you have any further questions on the use of this medicine, please ask your doctor or healthcare 
professional.

If you use more Hizentra than you should
If you think you have had too much Hizentra, speak to your doctor as soon as possible.

If you forget to use Hizentra
If you think you have missed a dose, speak to your doctor as soon as possible.

4. Possible side effects

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

► In isolated cases, you may be allergic (hypersensitive) to immunoglobulins and allergic 
reactions such as a sudden fall in blood pressure or shock may occur (e.g. you may feel light-



36

headed, dizzy, faint on standing, cold in the hands and feet, sense an abnormal heart beat or 
chest pain, or have blurred vision).

► In isolated cases, you may experience pain and/or swelling of an arm or leg with warmth over 
the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or 
discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on 
one side of the body, sudden confusion, or trouble speaking or understanding could be signs of a 
blood clot.

► In isolated cases, you may get a bad headache with nausea, vomiting, stiff neck, fever, and 
sensitivity to light, which could be signs of AMS (aseptic meningitis sydrome), which is a 
temporary reversible non-infectious inflammation of the membranes surrounding the brain and
the spinal cord.

 If you notice such signs during the infusion of Hizentra, stop the infusion and go to the 
nearest hospital immediately.

Please see also section 2 of this leaflet about the risk of allergic reactions, blood clots and AMS.

Side effects observed in controlled clinical studies are presented in order of decreasing frequency. Side 
effects observed in post-marketing are of unknown frequency:

The following side effects are very common (affects more than 1 patient in 10):
 Headache
 Rash
 Reactions at the infusion site

The following side effects are common (affects 1 to 10 patients in 100):
 Dizziness
 Migraine
 Increased blood pressure (hypertension)
 Diarrhoea
 Abdominal pain
 Feeling sick (nausea)
 Vomiting
 Itching (pruritus)
 Hives (urticaria)
 Pain related to the musculature and bones (musculoskeletal pain)
 Joint pain (arthralgia)
 Fever
 Tiredness (fatigue), including generally feeling unwell (malaise)
 Chest pain
 Flu-like symptoms
 Pain

The following side effects are uncommon (affects 1 to 10 patients in 1,000):
 Hypersensitivity
 Involuntary shaking movements in one or more parts of the body (tremor, including 

psychomotor hyperactivity)
 Fast heartbeat (tachycardia)
 Flushing
 Muscle spasm
 Muscular weakness
 Chills, including low body temperature
 Abnormal result of a blood test that may indicate impaired liver and kidney function

In isolated cases, infusion site ulcer or burning sensation may occur.



37

 You may reduce possible side effects if you infuse Hizentra slowly.

Side effects such as these may occur even when you have previously received human 
immunoglobulins and tolerated them well.

Please also refer to section 2 “What you need to know before you use Hizentra” for additional details 
on circumstances which increase the risk of side effect.

Reporting of side effects
If you get any side effects, talk to your doctor or healthcare professional. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Hizentra

 Keep this medicine out of the sight and reach of children.
 Do not use this medicine after the expiry date which is stated on the outer carton and the vial 

label after EXP.
 Because the solution contains no preservative, you must use/infuse it as soon as possible after 

opening the vial.
 Do not store above 25 °C.
 Do not freeze.
 Keep the vial in the outer carton in order to protect from light.
 Do not throw away any medicines via wastewater or household waste. Ask your healthcare 

professional how to throw away medicines you no longer use. These measures will help protect 
the environment.

6. Contents of the pack and other information

What Hizentra contains
 The active substance is human normal immunoglobulin. One ml contains 200 mg of human 

normal immunoglobulin, of which at least 98% is immunoglobulin type G (IgG).
The approximate percentage of IgG subclasses is as follows:
IgG1 ............. 69%
IgG2 ............. 26%
IgG3 ............. 3%
IgG4 ............. 2%
This medicine contains trace amounts of IgA (not more than 50 micrograms /ml).
Hizentra is essentially sodium free.

 The other ingredients (excipients) are L-proline, polysorbate 80 and water for injections.

What Hizentra looks like and contents of the pack
Hizentra is a solution for subcutaneous injection (200 mg/ml). The colour can vary from pale-yellow 
to light-brown.
Hizentra is available in vials of 5, 10, 20 or 50 ml.
Hizentra is also available in pre-filled syringes of 5 and 10 ml.

Pack sizes
Packs of 1, 10 or 20 vials

Hizentra is also available in packs of 1 or 10 pre-filled syringes.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


38

Please note that alcohol swabs, needles and other supplies or equipment are not contained in the pack.

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
Tél/Tel: +32 15 28 89 20

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20

България
Ей енд Ди Фарма България ЕАД
Тел: +359 2 810 3949 

Magyarország
CSL Behring Kft.
Tel: +36 1 213 4290

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Eesti
CSL Behring GmbH
Tel: +49 69 30584437

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Polska
CSL Behring Sp. z o.o.
Tel: +48 22 213 22 65

España
CSL Behring S.A.
Tel: +34 933 67 1870

Portugal
CSL Behring Lda
Tel: +351 21 782 62 30

France
CSL Behring SA
Tél: + 33 1 53 58 54 00

Hrvatska
Marti Farm d.o.o
Tel: +385 1 5588297

România
Prisum International Trading srl

Tel: +40 21 322 01 71

Slovenija
MediSanus d.o.o.
Tel: +386 1 25 71 496



39

Ireland
CSL Behring GmbH
Tel: +49 69 305 17254

Slovenská republika
CSL Behring s.r.o. 
Tel: +421 911 653 862

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

United Kingdom
CSL Behring UK Ltd.
Tel: +44 (0)1444 447405

Latvija
CSL Behring GmbH
Tel: +49 69 30584437

Lietuva
CSL Behring GmbH
Tel: +49 69 30584437

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

---------------------------------------------------------------------------------------------------------------------------



40

Package leaflet: Information for the user

Hizentra 200 mg/ml solution for subcutaneous injection in pre-filled syringe
Human normal immunoglobulin (SCIg = Subcutaneous Immunoglobulin)

Read all of this leaflet carefully before you start using this medicine, because it contains 
important information for you.

 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor or healthcare professional.
 This medicine has been prescribed for you only. Do not pass it on to others.

It may harm them, even if their signs of illness are the same as yours.
 If you get any side effects talk to your healthcare professional. This includes any possible side 

effects not listed in this leaflet. See section 4.

What is in this leaflet
1. What Hizentra is and what it is used for
2. What you need to know before you use Hizentra
3. How to use Hizentra
4. Possible side effects
5. How to store Hizentra
6. Contents of the pack and other information

1. What Hizentra is and what it is used for

What Hizentra is
Hizentra belongs to the class of medicines called human normal immunoglobulins. Immunoglobulins 
are also known as antibodies and are blood proteins that help your body to fight infections.

How Hizentra works
Hizentra contains immunoglobulins that have been prepared from the blood of healthy people. 
Immunoglobulins are produced by human body’s immune system. They help your body to fight 
infections caused by bacteria and viruses or maintain the balance in your immune system (referred to 
as immunomodulation). The medicine works in exactly the same way as the immunoglobulins 
naturally present in your blood.

What Hizentra is used for
Replacement therapy
Hizentra is used to raise abnormally low immunoglobulin levels in your blood to normal levels
(replacement therapy). The medicine is used in adults and children (0-18 years) in the following
situations:

1. Treatment of patients who are born with a reduced ability or inability to produce immunoglobulins 
(primary immunodeficiencies). This includes conditions such as:
 low immunoglobulin levels (hypogammaglobulinaemia) or absence of immunoglobulins 

(agammaglobulinaemia) in the blood
 combination of low immunoglobulin levels, frequent infections and inability to produce 

adequate amounts of antibodies after vaccination (common variable immunodeficiency)
 combination of low level or absence of immunoglobulins and absence or non-functional 

immune cells (severe combined immunodeficiency)
 lack of certain immunoglobulin G subclasses causing recurrent infections.

2. Treatment of low immunoglobulin levels and recurrent bacterial infections in patients with
chronic lymphocytic leukaemia (CLL), a certain kind of blood cancer, where prophylactic 
antibiotics have failed or are contra-indicated.



41

3. Treatment of low immunoglobulin levels and recurrent bacterial infections in patients with 
multiple myeloma (MM), another kind of blood cancer.

4. Treatment of low immunoglobulin levels in patients pre- and post- allogeneic haematopoietic 
stem cell transplantation (HSCT).

Immunomodulatory therapy in CIDP patients
Hizentra is also used in patients with chronic inflammatory demyelinating polyneuropathy (CIDP), a 
form of autoimmune disease. CIDP is characterised by chronic inflammation of the peripheral nerves 
that causes muscle weakness and/or numbness mainly in the legs and arms. It is believed that the 
body’s defense attack underlines such inflammation, and the immunoglobulins present in Hizentra 
help to protect the nerves from being attacked (immunomodulatory therapy).

2. What you need to know before you use Hizentra

Do NOT infuse Hizentra
► if you are allergic to human immunoglobulins, polysorbate 80 or L-proline.

 Tell your doctor or healthcare professional prior to treatment if you have experienced an
intolerance against one of these components earlier.

► if you suffer from hyperprolinaemia (a genetic disorder causing high levels of the amino acid 
proline in the blood).

► into a blood vessel.

Warnings and precautions
 Talk to your doctor or healthcare professional before using Hizentra.

You may be allergic (hypersensitive) to immunoglobulins without knowing it. However, true allergic 
reactions are rare. They may occur even if you received human immunoglobulins previously and 
tolerated them well. It may happen particularly if you do not have enough of the immunoglobulin type
A (IgA) in your blood (IgA deficiency).
 Tell your doctor or healthcare professional prior to treatment if you have an immunoglobulin 

type A (IgA) deficiency. Hizentra contains residual amounts of IgA which might cause an
allergic reaction.

In these rare cases allergic reactions, such as a sudden fall in blood pressure or shock may occur (see 
also section 4 “Possible side effects”).
 If you notice such signs during the infusion of Hizentra, stop the infusion and contact your 

doctor or go to the nearest hospital immediately.

 Tell your doctor if you have a history of heart or blood vessel disease or blood clots, have thick 
blood, or have been immobile for some time. These things may increase your risk of having a blood 
clot after using Hizentra. Also tell your doctor what drugs you are using, as some drugs, such as those 
that contain the hormone estrogen (for example, birth control pills), may increase your risk of 
developing a blood clot. Contact your doctor immediately if you experience signs and symptoms such 
as shortness of breath, chest pain, pain and swelling of a limb, weakness or numbness on one side of 
the body after receiving Hizentra.

 Contact your doctor if you experience the following signs and symptoms: severe headache, neck 
stiffness, drowsiness, fever, photophobia, nausea, and vomiting after receiving Hizentra. Your doctor 
will decide if further tests are necessary and whether Hizentra should be continued.

Your healthcare professional will avoid potential complications by ensuring:
► that you are not sensitive to human normal immunoglobulin.

The medicine must be infused slowly at first. The recommended infusion rate given under 
section 3 “How to use Hizentra” must be closely followed.



42

► that you are carefully monitored for any symptoms throughout the infusion period, especially if:
 you receive human normal immunoglobulin for the first time
 you have switched from a different medicine
 there has been a long interval (more than eight weeks) since the previous infusion.
In these cases, it is recommended that you are monitored during the first infusion and for an 
hour afterwards. If the points above do not apply for you it is recommended that you are 
observed for at least 20 minutes after administration.

Other medicines and Hizentra
 Tell your doctor or healthcare professional if you are using, have recently used or might use any 

other medicines.
 You must not mix other medicines with Hizentra.
 Tell your vaccinating doctor prior to a vaccination about your treatment with Hizentra.

Hizentra may impair the effect of some live virus vaccines such as measles, rubella, mumps and 
chicken pox. Therefore, after receiving this medicine you may have to wait up to 3 months 
before receiving your live-attenuated vaccine. In the case of measles vaccinations the 
impairment may persist for up to 1 year.

Pregnancy, breast-feeding and fertility
 Tell your doctor or healthcare professional if you are pregnant, plan to become pregnant or are 

breast-feeding. Your doctor will decide whether you can receive Hizentra during your 
pregnancy or while you are breast-feeding.

No clinical studies have been performed with Hizentra in pregnant women. However, medicines that 
contain immunoglobulins have been used in pregnant or breast-feeding women for years, and no 
harmful effects on the course of pregnancy or on the baby have been observed.

If you are breast-feeding and receive Hizentra, the immunoglobulins of the medicine can also be found 
in the breast milk. Therefore, your baby may be protected from certain infections.

Driving and using machines
Patients may experience effects, such as dizziness or nausea, during treatment with Hizentra that might 
affect the ability to drive and use machines. If this happens, you should not drive or use machines until 
these effects have disappeared.

Hizentra contains proline
You must not take it if you suffer from hyperprolinaemia (see also section 2 “What you need to know 
before you use Hizentra”). Please tell your doctor prior to treatment.

Other important information about Hizentra
Blood tests
After receiving Hizentra, the results of certain blood tests (serological tests) may be impaired for a 
certain time.
 Tell your doctor about your treatment with Hizentra prior to any blood test.

Information on what Hizentra is made of
Hizentra 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 medicines also include steps in the processing of the blood or plasma that can 
inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or 
plasma are administered, the possibility of passing on infection cannot be totally excluded. This also 
applies to any unknown or emerging viruses or other types of infections.



43

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

 It is strongly recommended that every time you receive a dose of Hizentra the name and batch 
number of the product are recorded in order to maintain a record of the batches used (see section 
3 “How to use Hizentra”).

3. How to use Hizentra

Always use this medicine exactly as your doctor has told you. Check with your doctor if you are not 
sure.

Dosage
Your doctor will calculate the correct dose for you taking into account your weight and response to 
treatment.
The dose or dosing interval should not be changed without consulting your doctor.
If you think you should receive Hizentra more or less frequently, please speak to your doctor.
If you think you have missed a dose, speak to your doctor as soon as possible.

Replacement therapy
Your doctor will determine whether you need a loading dose (for adults and children) of at least 1 to 
2.5 ml/kg of body weight divided over several days. Following this, maintenance doses may be given
at repeated intervals, from daily to once every two weeks, to reach a cumulative monthly dose of about 
2 to 4 ml/kg of body weight. Your healthcare professional may adjust the dose based on your response 
to the treatment.

Immunomodulatory therapy
Your doctor will initiate therapy with Hizentra 1 week after your last intravenous immunoglobulin 
infusion by administrating under the skin (subcutaneously) with a weekly dose of 1.0 to 2.0 ml/kg of 
body weight. Your doctor will determine your weekly Hizentra dose. The weekly maintenance doses 
may be divided into smaller doses and administered as often as required during the week. For dosing 
every two weeks, your doctor will double the weekly Hizentra dose. Your healthcare professional may 
adjust the dose based on your response to the treatment.

Method and route of administration
In case of home treatment, this will be initiated by a healthcare professional experienced in the 
treatment of immunodeficiency/CIDP with SCIg and in the guidance of patients for home treatment.

You will be instructed in:
 aseptic infusion techniques
 the keeping of a treatment diary, and
 measures to be taken in case of severe side effects.

Infusion site(s)
 Administer Hizentra under the skin only.
 You may infuse Hizentra into sites such as abdomen, thigh, upper arm, and lateral hip. If large 

doses are given (> 50 ml), try to administer them at multiple sites.
 You may use an unlimited number of sites simultaneously. Injection sites should be at least 

5 cm apart.
 In the case, you will use a device-assisted infusion technique (e.g. pump-assisted infusion), 

more than one infusion device can be used simultaneously.



44

 In the case, you will use the manual push infusion technique with a syringe, you may use only 
one infusion site per syringe. If you need to administer an additional Hizentra syringe, you must 
use a new sterile injection needle and change the infusion site.

 The volume of product infused into a particular site may vary.

Infusion rate(s)
Your doctor will determine the appropriate infusion technique and the infusion rate for you taking into 
account your individual dose, dosing frequency and product tolerability.

Device-assisted infusion:
The recommended initial infusion rate is up to 20 ml/hour/site. If well-tolerated, you may gradually 
increase the infusion rate to 35 ml/hour/site for the subsequent two infusions. Thereafter, the infusion 
rate can be increased further as per your tolerability.

Manual push infusion:
The recommended initial infusion rate is up to 0.5 ml/min/site (30 ml/hour/site). If well-tolerated, you 
may increase the infusion rate up to 2.0 ml/min/site (120 ml/hour/site) for subsequent infusions.
Thereafter, the infusion rate can be increased further as per your tolerability.

Instructions for use

Follow the steps below and use aseptic technique to administer Hizentra.
1 Clean surface

Thoroughly clean a table or other flat surface using an antiseptic wipe.
2 Assemble supplies

Place Hizentra and other supplies and equipment needed for the infusion on a clean, flat surface.
3 Thoroughly wash and dry hands
4 Check blistered pre-filled syringes

Visually inspect Hizentra for particles in the solution or discoloration as well as expiry date before 
administering Hizentra. Do not use solutions that are cloudy or contain particles. Do not use 
solutions that have been frozen. Administer solution which is at room or body temperature.
Once a blistered pre-filled syringe has been opened, use the solution immediately.

5 Preparation of Hizentra for infusion
The 5 ml and 10 ml pre-filled syringes are 
supplied fully assembled and ready to use. 

All pre-filled syringes have a standard luer 
lock, which is a screw connection at the 
syringe tip that creates a leak-free seal.

If you are using a syringe pump, Hizentra pre-filled syringes can be 
placed directly in the syringe pump if the syringe size matches the 
pump requirements. 

If the pre-filled syringe can be placed directly on the pump, then go 
to Step 6.

If the Hizentra pre-filled syringe size does not match the pump 
requirements, then the contents of the pre-filled syringe can be 
transferred to another syringe of a size specific for the pump.

6 Prepare the tubing
Attach the administration tubing or needle set to the syringe. Prime the tubing to eliminate all 
remaining air.



45

7 Prepare infusion site(s)
Select the infusion site(s) – The number and location of infusion
sites depends on the volume of the total dose. Each infusion site 
should be at least 5 cm apart.
You may use an unlimited number of sites simultaneously.

Clean the infusion site(s) using an antiseptic skin preparation, 
Allow each site to dry before proceeding.

8 Insert the needle
Grasp the skin between 2 fingers and insert the needle into the 
subcutaneous tissue.

Secure the needle to the skin – If necessary, use gauze and tape or 
transparent dressing to hold the needle in place.

9 Infuse Hizentra
Start infusion.
If using an infusion pump, follow the manufacturer’s instructions.

10 Record the infusion
Record the following data in your treatment diary:
• the date of administration,
• the batch number of the medicine, and
• the infused volume, flow rate, the number and location of infusion sites.

11 Clean up
Discard any unused product and all used administration supplies after administration in accordance 
with local requirements.

If you have any further questions on the use of this medicine, please ask your doctor or healthcare 
professional.

If you use more Hizentra than you should
If you think you have had too much Hizentra, speak to your doctor as soon as possible.

If you forget to use Hizentra
If you think you have missed a dose, speak to your doctor as soon as possible.

4. Possible side effects

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

► In isolated cases, you may be allergic (hypersensitive) to immunoglobulins and allergic 
reactions such as a sudden fall in blood pressure or shock may occur (e.g. you may feel light-
headed, dizzy, faint on standing, cold in the hands and feet, sense an abnormal heart beat or 
chest pain, or have blurred vision).



46

► In isolated cases, you may experience pain and/or swelling of an arm or leg with warmth over 
the affected area, discoloration of an arm or leg, unexplained shortness of breath, chest pain or 
discomfort that worsens on deep breathing, unexplained rapid pulse, numbness or weakness on 
one side of the body, sudden confusion, or trouble speaking or understanding could be signs of a 
blood clot.

► In isolated cases, you may get a bad headache with nausea, vomiting, stiff neck, fever, and 
sensitivity to light, which could be signs of AMS (aseptic meningitis sydrome), which is a 
temporary reversible non-infectious inflammation of the membranes surrounding the brain and 
the spinal cord.

 If you notice such signs during the infusion of Hizentra, stop the infusion and go to the 
nearest hospital immediately.

Please see also section 2 of this leaflet about the risk of allergic reactions, blood clots and AMS.

Side effects observed in controlled clinical studies are presented in order of decreasing frequency. Side 
effects observed in post-marketing are of unknown frequency:

The following side effects are very common (affects more than 1 patient in 10):
 Headache
 Rash
 Reactions at the infusion site

The following side effects are common (affects 1 to 10 patients in 100):
 Dizziness
 Migraine
 Increased blood pressure (hypertension)
 Diarrhoea
 Abdominal pain
 Feeling sick (nausea)
 Vomiting
 Itching (pruritus)
 Hives (urticaria)
 Pain related to the musculature and bones (musculoskeletal pain)
 Joint pain (arthralgia)
 Fever
 Tiredness (fatigue), including generally feeling unwell (malaise)
 Chest pain
 Flu-like symptoms
 Pain

The following side effects are uncommon (affects 1 to 10 patients in 1,000):
 Hypersensitivity
 Involuntary shaking movements in one or more parts of the body (tremor, including 

psychomotor hyperactivity)
 Fast heartbeat (tachycardia)
 Flushing
 Muscle spasm
 Muscular weakness
 Chills, including low body temperature
 Abnormal result of a blood test that may indicate impaired liver and kidney function

In isolated cases, infusion site ulcer or burning sensation may occur.

 You may reduce possible side effects if you infuse Hizentra slowly.



47

Side effects such as these may occur even when you have previously received human 
immunoglobulins and tolerated them well.

Please also refer to section 2 “What you need to know before you use Hizentra” for additional details 
on circumstances which increase the risk of side effect.

Reporting of side effects
If you get any side effects, talk to your doctor or healthcare professional. This includes any possible 
side effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Hizentra

 Keep this medicine out of the sight and reach of children.
 Do not use this medicine after the expiry date which is stated on the outer carton and the pre-

filled syringe label after EXP.
 Because the solution contains no preservative, you must use/infuse it as soon as possible after 

opening the blistered pre-filled syringe.
 Do not store above 25 °C.
 Do not freeze.
 Keep the blistered pre-filled syringe in the outer carton in order to protect from light.
 Do not throw away any medicines via wastewater or household waste. Ask your healthcare 

professional how to throw away medicines you no longer use. These measures will help protect 
the environment.

6. Contents of the pack and other information

What Hizentra contains
 The active substance is human normal immunoglobulin. One ml contains 200 mg of human 

normal immunoglobulin, of which at least 98% is immunoglobulin type G (IgG).
The approximate percentage of IgG subclasses is as follows:
IgG1 ............. 69%
IgG2 ............. 26%
IgG3 ............. 3%
IgG4 ............. 2%
This medicine contains trace amounts of IgA (not more than 50 micrograms /ml).
Hizentra is essentially sodium free.

 The other ingredients (excipients) are L-proline, polysorbate 80 and water for injections.

What Hizentra looks like and contents of the pack
Hizentra is a solution for subcutaneous injection (200 mg/ml). The colour can vary from pale-yellow 
to light-brown.
Hizentra is available in pre-filled syringes of 5 or 10 ml.
Hizentra is also available in vials of 5, 10, 20 and 50 ml.

Pack sizes
Packs of 1 or 10 pre-filled syringes.
Hizentra is also available in packs of 1, 10 or 20 vials.

Please note that alcohol swabs, needles and other supplies or equipment are not contained in the pack.

Not all pack sizes may be marketed.

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


48

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
Tél/Tel: +32 15 28 89 20

Luxembourg/Luxemburg
CSL Behring NV
Tél/Tel: +32 15 28 89 20

България
Ей енд Ди Фарма България ЕАД
Тел: +359 2 810 3949 

Magyarország
CSL Behring Kft.
Tel: +36 1 213 4290

Česká republika
CSL Behring s.r.o.
Tel: + 420 702 137 233

Malta
AM Mangion Ltd.
Tel: +356 2397 6333

Danmark
CSL Behring AB
Tel: +46 8 544 966 70

Nederland
CSL Behring BV
Tel: + 31 85 111 96 00

Deutschland
CSL Behring GmbH
Tel: +49 69 30584437

Norge
CSL Behring AB
Tlf: +46 8 544 966 70

Eesti
CSL Behring GmbH
Tel: +49 69 30584437

Österreich
CSL Behring GmbH
Tel: +43 1 80101 2463

Ελλάδα
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

Polska
CSL Behring Sp. z o.o.
Tel: +48 22 213 22 65

España
CSL Behring S.A.
Tel: +34 933 67 1870

Portugal
CSL Behring Lda
Tel: +351 21 782 62 30

France
CSL Behring SA
Tél: + 33 1 53 58 54 00

Hrvatska
Marti Farm d.o.o.
Tel: +385 1 5588297

România
Prisum International Trading srl

Tel: +40 21 322 01 71

Slovenija
MediSanus d.o.o.
Tel: +386 1 25 71 496

Ireland
CSL Behring GmbH
Tel: +49 69 305 17254

Slovenská republika
CSL Behring s.r.o. 
Tel: +421 911 653 862



49

Ísland
CSL Behring AB
Sími: +46 8 544 966 70

Suomi/Finland
CSL Behring AB
Puh/Tel: +46 8 544 966 70

Italia
CSL Behring S.p.A.
Tel: +39 02 34964 200

Sverige
CSL Behring AB
Tel: +46 8 544 966 70

Κύπρος
CSL Behring ΕΠΕ
Τηλ: +30 210 7255 660

United Kingdom
CSL Behring UK Ltd.
Tel: +44 (0)1444 447405

Latvija
CSL Behring GmbH
Tel: +49 69 30584437

Lietuva
CSL Behring GmbH
Tel: +49 69 30584437

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu/.

---------------------------------------------------------------------------------------------------------------------------


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER OF THE BIOLOGICAL ACTIVE SUBSTANCE AND MANUFACTURER RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET