Zutectra

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ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 



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1. NAME OF THE MEDICINAL PRODUCT 
 
Zutectra 500 IU solution for injection in pre-filled syringe 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One pre-filled syringe of 1 ml contains Human hepatitis B immunoglobulin 500 IU. 
 
Human protein 150 mg/ml of which at least 96 % is IgG, with a content of antibodies to hepatitis B 
virus surface antigen (HBs) of 500 IU/ml. 
 
Distribution of IgG subclasses: 
IgG1:  59 % 
IgG2:  35 % 
IgG3: 3 % 
IgG4: 3 % 
 
The maximum IgA content  is 6,000 micrograms/ml. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection  
 
The solution is clear and pale yellow or light brown. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Prevention of hepatitis B virus (HBV) re-infection in HBsAg and HBV-DNA negative adult patients at 
least one week after liver transplantation for hepatitis B induced liver failure. HBV-DNA negative 
status should be confirmed within the last 3 months prior to OLT. Patients should be HBsAg negative 
before treatment start. 
  
The concomitant use of adequate virostatic agents should be considered as standard of hepatitis B re-
infection prophylaxis. 
 
4.2 Posology and method of administration 
 
Posology 
In HBV-DNA negative adults at least one week after liver transplantation subcutaneous injections of 
Zutectra per week or fortnightly according to serum anti-HBs trough levels.  
 
Prior to the initiation of subcutaneous treatment with Zutectra adequate anti-HBs serum levels should 
be stabilised with an intravenous hepatitis B immunoglobulin to levels at or above 300-500 IU/l in 
order to ensure adequate anti-HBs coverage during the transition from intravenous to subcutaneous 
dosing.  Antibody levels >100 IU/l should be maintained in HBsAg and HBV-DNA negative patients.  
 
The dose can be individually established and adapted from 500 IU up to 1,000 IU (in exceptional cases 
up to 1,500 IU) subcutaneous injections on a weekly or fortnightly basis, according to the serum anti-
HBs concentrations and at the discretion of the physician in charge. Antibody levels >100 IU/l should 
be maintained. 



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Patients must be monitored for serum anti-HBs antibody levels regularly. Serum anti-HBs antibody 
levels should be measured at least every 2-4 weeks and at the discretion of the physician in charge for 
at least half a year. 
 
Paediatric population 
There is no relevant indication for use of Zutectra in children under the age of 18. 
 
Method of administration 
 
For subcutaneous use only. 
 
Precautions to be taken before handling or administering the medicinal product 
Injection of the medicinal product by the patient or by caregiver in a home treatment requires training 
by a physician experienced in the guidance of patients for home treatment. The patient or caregiver 
will be instructed in injection techniques, the keeping of a treatment diary and measures to be taken in 
case of severe adverse events. A sufficient surveillance period with stable anti-HBs trough serum 
levels of > 100 IU/l as well as a fixed dosage regimen is required: the monitoring schedule of patients 
anti-HBs antibody levels (see above) needs to be closely followed. In addition patient or caregiver 
must comply with the injection technique as well as with the dosing regimen to ensure anti-HBs 
trough serum levels > 100 IU/l after extended periods between level controls. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or to human 
immunoglobulins. 
 
Zutectra must not be administered intravascularly. 
 
4.4 Special warnings and precautions for use 
 
Ensure that Zutectra is not administered into a blood vessel, because of the risk of shock. 
 
If the recipient is a carrier of HBsAg, there is no benefit in administering this medicinal product. 
 
There is no data about efficacy in post-exposure prophylaxis. 
 
Hypersensitivity 
 
True hypersensitivity reactions are rare. 
 
Zutectra contains a small quantity of IgA. Individuals who are deficient in IgA have the potential for 
developing IgA antibodies and may have anaphylactic reactions after administration of blood 
components containing IgA. The physician must therefore weigh the benefit of treatment with Zutectra 
against the potential risk of hypersensitivity reactions. 
 
Rarely, human hepatitis B immunoglobulin can induce a fall in blood pressure with anaphylactic 
reaction, even in patients who have tolerated previous treatment with human immunoglobulin. 
 
Potential complications can often be avoided by ensuring that patients: 
- are not sensitive to human normal immunoglobulin, by initially injecting the product slowly; 
- are carefully monitored for any symptoms throughout the injection. In particular, patients naive 

to human normal immunoglobulin, patients switched from an alternative product or when there 
has been a long interval since the previous injection should be monitored during the first 
injection and for the first hour after the first injection, in order to detect potential adverse signs. 
All other patients should be observed for at least 20 minutes after administration. 

 



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Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the 
injection. In case of shock, standard medical treatment for shock should be implemented. 
 
Interference with serological testing 
 
After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in 
the patient’s blood may result in misleading positive results in serological testing. 
 
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some 
serological tests for red cell antibodies, for example the direct antiglobulin test (DAT, direct Coombs’ 
test). 
 
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 human immunodeficiency 
virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV), and for the non-enveloped hepatitis 
A virus (HAV). The measures taken may be of limited value against non-enveloped viruses such as 
parvovirus B19. 
 
There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 
transmission with immunoglobulins and it is also assumed that the antibody content makes an 
important contribution to the viral safety. 
 
It is strongly recommended that every time that Zutectra is administered to a patient, the name and 
batch number of the medicinal product are recorded in order to maintain a link between the patient and 
the batch of the medicinal product. This recommendation applies also for documentation in the 
treatment diary during self-administration of the medicinal product in a home treatment. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
Live attenuated virus vaccines 
 
Immunoglobulin administration may interfere with the development of an immune response to live 
attenuated virus vaccines such as rubella, mumps, measles and varicella for a period of 3 months. 
After administration of this medicinal product, an interval of at least 3 months should elapse before 
vaccination with live attenuated virus vaccines. 
 
Human hepatitis B immunoglobulin should be administrated three to four weeks after vaccination with 
such a live attenuated vaccine; in case administration of human hepatitis B immunoglobulin is 
essential within three to four weeks after vaccination, then revaccination should be performed three 
months after the administration of human hepatitis B immunoglobulin. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
The safety of this medicinal product for use in human pregnancy has not been established in controlled 
clinical trials and therefore should only be given with caution to pregnant women. Clinical experience 
with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus 
and the neonate are to be expected. 



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Breast-feeding 
 
The safety of this medicinal product for use in breast-feeding has not been established in controlled 
clinical trials and therefore should only be given with caution to breast-feeding mothers. 
 
Fertility 
 
No fertility studies have been performed (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Hepatitis B immunoglobulin has no or negligible influence on the ability to drive and use machines. 
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
Most adverse drug reactions (ADRs) were mild to moderate in nature. In isolated cases human normal 
immunoglobulins may cause an anaphylactic shock. 
 
Tabulated list of adverse reactions 
 
The following adverse reactions have been reported in the context of 4,810 subcutaneous applications 
of Zutectra during four completed clinical trials and 1,006 applications during a non-interventional 
post marketing safety study (PASS). 
The ADRs reported in four trials are summarised and categorised according to the MedDRA system 
organ class and frequency below. Frequency per injection 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), not known (cannot be estimated from the available 
data). 
 
The effects were grouped by system organ classes under relevant medical headings. 
 
MedDRA System 
Organ Class 

Adverse reactions Frequency 

Infections and infestations Nasopharyngitis Rare*  
Immune system disorders Hypersensitivity Rare* 
Nervous system disorders Headache Uncommon 
Cardiac disorders Palpitations, cardiac discomfort Rare* 
Vascular disorders Hypertension Rare*  
Respiratory, thoracic and 
mediastinal disorders 

Oropharyngeal pain Rare*  

Gastrointestinal disorders Upper abdominal pain Uncommon 
Skin and subcutaneous tissue 
disorders 

Pruritus, rash Rare* 

Musculosceletal and connective 
tissue disorders 

Muscle spams Rare*  

General disorders and 
administration site conditions 

Injection site reactions like pain, 
urticaria at injection site, 
haematoma and erythema 

Common 

Fatigue, tiredness Rare*  
*  single case reports 
 
Adverse reactions observed with other human immunoglobulin preparations 
 



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With normal immunoglobulins adverse reactions such as chills, headache, dizziness, 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 injection sites  
Swelling, soreness, redness, induration, local heat, itching, bruising and rash. 
 
For safety information with respect to transmissible agents, see section 4.4. 
 
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, Specific immunoglobulins, Hepatitis 
B immunoglobulin  
ATC code: J06BB04 
 
Hepatitis B immunoglobulin contains mainly immunoglobulin G (IgG) with a specifically high content 
of antibodies against hepatitis B virus surface antigen (HBs). 
 
Clinical efficacy and safety 
 
The open, prospective, single-arm clinical trial  enrolled 23 liver transplant recipients, who had been 
receiving intravenous hepatitis B immunoglobulin prophylaxis and subsequently switched to 
subcutaneous Zutectra. The weekly subcutaneous dose was 500 IU for patients with bodyweight 
< 75 kg (a dose increase to 1000 IU was allowed, if medically required to maintain a safety level of 
> 100 IU) and 1000 IU for patients with bodyweight ≥ 75 kg. 2 patients received a higher and 
2 patients received a lower dose than recommended by the weight based dosing regimen. Serum anti-
HBs trough levels of 100 IU/l and higher (primary efficacy endpoint) were maintained for all patients 
during the 18 to 24 week trial period. The > 100 IU/l safety margin is the generally accepted level of 
effective prevention against HBV re-infection in liver transplant patients at risk. No patient 
experienced HBV re-infection. Self-administration was feasible for most patients. 
 
The mean anti-HBs serum level before switching was 393 ± 139 IU/l. All patients used antiviral 
medicine. 
 
Using the Clopper Pearson method, the failure rate after 18 weeks was 0 % for patients of the ITT set 
(95 % CI: [0, 14.8 %]). A failure rate of 0 % was also found for the facultative extension phase 
(week 24) (95 % CI: [0, 20.6 %]) 
 



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The objectives of the open, prospective, single-arm clinical trial were the investigation of feasibility of 
home self-administration (including patient compliance), efficacy and safety of subcutaneous 
application of Zutectra in a population of stable patients during long-term treatment for prophylaxis 
against re-infection of a transplanted liver in 66 patients. All patients included in this study had to run 
through a training period of at least 29 days and home self-administration could start on day 36 at the 
earliest. With the exception of 6 patients who withdrew prior to day 36, all patients achieved complete 
hospital and home self-administration. No patient prematurely discontinued the study due to lack of 
feasibility of home self-treatment. During the 48-weeks treatment phase constant serum HBs antibody 
concentrations ≥ 100 IU/l were measured in all patients at all assessments with mean values of 
312.0 ± 103.5 IU/l at the end of the treatment period. In total, 53/66 patients (80.3 %) used antiviral 
medication and 13 patients received monotherapy with Zutectra during this study. No hepatitis B re-
infection was reported and no patient was tested HBsAg positive during the treatment period of 
48 weeks. No serious adverse events were reported to be related to study medication. No fatal case 
was observed during the study. 
 
The objective of the open, prospective, single-arm clinical trial was the investigation of efficacy and 
safety of Zutectra for prevention of hepatitis B virus (HBV) re-infection ≥ one week after orthotopic 
liver transplantation in HBsAg and HBV-DNA negative patients. At the time of transplantation 21 
patients (42.9%) were tested positive for HDV, patients with a positive HIV or HCV test were 
excluded from study participation. 49 patients received subcutaneous injections of Zutectra of 500 IU 
(1 mL) or 1,000 IU (2 mL) (dose adaptation in exceptional cases up to 1,500 IU) per week or 
fortnightly according to serum anti-HBs trough levels. The individual treatment duration per patient 
was planned to be up to 24 weeks after transplantation. No treatment failures occurred during the 6-
month study period. Serum HBs antibody concentrations above the minimum safety trough level of 
>100 IU/L were measured in all patients at all timepoints independent of the type of administration 
(investigator, caregiver or self-injection), the dose regimen (500 IU, 1000 IU, 1500 IU) or the 
treatment intervals. No clinical signs of a hepatitis B re-infection were observed and no patient was 
tested HBsAg positive or HBV-DNA positive during the study which confirms that effective 
protection against Hepatitis B virus re-infection was provided by subcutaneous administration of 
Zutectra as part of the combination treatment with HBV virostatic therapy 8 – 18 days after orthotopic 
liver transplantation. One non-serious adverse event was reported to be related to Zutectra (injection 
site haematoma). No fatal case was observed during the study. 
 
The non-interventional post authorization safety study (PASS 978) enrolled 61 adult patients 
≥ 6 months after liver transplantation for hepatitis B induced liver failure. The objective of the study 
was to evaluate the level of compliance of patients using subcutaneous Zutectra as home self- 
treatment for preventing hepatitis B re-infection. Patients were to be treated with Zutectra in 
accordance with the information and dosage given in the SPC. Compliance according to anti-HBs 
serum levels could be shown for 57 (of 61) patients (93%), with no values below 100 IU/l and a mean 
anti-HBs serum level of 254.3 IU/l at the final visit. In total, 42/61 patients (68.9 %) used antiviral 
medication and 19 patients received monotherapy with Zutectra during this study. No treatment failure 
defined as positive HBV-DNA and HBsAg findings occurred during the entire observation period. No 
re-infection was observed. No serious adverse reaction was reported. No fatal case was observed 
during the study. 
 
5.2 Pharmacokinetic properties 
 
Distribution 
 
Zutectra is slowly absorbed into the recipient’s circulation and reaches a maximum after a delay of 
2-7 days. 
 
Biotransformation 
 
IgG and IgG-complexes are broken down in the reticuloendothelial system. 
 



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Elimination 
 
Zutectra has a half-life of about 3-4 weeks. This half-life may vary from patient to patient. 
 
5.3 Preclinical safety data 
 
Immunoglobulins are normal constituents of the human body, therefore toxicity testing in 
heterologous species is of no relevance. 
 
In a local tolerance trial in rabbits, there was no evidence of irritation attributable to Zutectra. 
 
No other non-clinical trials have been carried out. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Glycine 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
No other preparations may be added to the Zutectra solution as any change in the electrolyte 
concentration or the pH may result in precipitation or denaturisation of the proteins. 
 
6.3 Shelf life 
 
2 years. 
 
The solution should be administered immediately after opening the syringe. 
 
6.4 Special precautions for storage 
 
Store and transport refrigerated (2°C-8°C). 
 
Do not freeze. 
 
Keep the container in the outer carton in order to protect from light. 
 
6.5 Nature and contents of container 
 
One ml solution in a pre-filled syringe (Type I glass) with a stopper (bromobutyl) and a tip cap 
(bromobutyl rubber). 
 
Pack size of five syringes in a blistered pack. 
 
6.6 Special precautions for disposal and other handling 
 
This medicinal product should be brought to room temperature (approx. 23°C-27°C) before use. 
 
The solution can vary from colourless to pale yellow up to light brown.  
 
Solutions that are cloudy or have deposits should not be used. 



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Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Biotest Pharma GmbH 
Landsteinerstrasse 5 
D-63303 Dreieich 
Germany 
Tel.: +49 6103 801-0 
Fax: +49 6103 801-150 
Email: mail@biotest.com 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/600/001 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
30/11/2009 / 16/09/2014 
 
 
10. DATE OF REVISION OF THE TEXT 
 
Detailed information on this medicine is available on the website of the European Medicines Agency 
http://www.ema.europa.eu.  



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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 



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

 
Name and address of the manufacturer of the biological active substance 
 
Biotest AG 
Landsteinerstr. 5 
D-63303 Dreieich 
Germany 
 
 
Name and address of the manufacturer responsible for batch release 
 
Biotest Pharma GmbH 
Landsteinerstrasse 5 
D-63303 Dreieich 
Germany 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to medical prescription. 
 
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 
The requirements for submission of periodic safety update reports 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 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. 

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



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ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



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A. LABELLING 
  



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PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER BOX 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zutectra 500 IU solution for injection in pre-filled syringe 
Human hepatitis B immunoglobulin 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
1 ml contains: 
Human protein 150 mg of which at least 96 % is IgG, with a content of antibodies to hepatitis B virus 
surface antigen (HBs) of 500 IU. 
 
IgG subclass distribution: 
59 % IgG1, 35 % IgG2, 3 % IgG3, 3 % IgG4 
IgA content ≤ 6,000 micrograms/ml 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Glycine, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
5 pre-filled syringes 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
 
For subcutaneous use only.  
 
 
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 
 
 
8. EXPIRY DATE 
 
EXP  
The solution should be administered immediately after opening the syringe. 
 
 



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9. SPECIAL STORAGE CONDITIONS 
 
Store and transport refrigerated (2°C-8°C). 
Do not freeze. 
Keep the container 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 
 
Biotest Pharma GmbH 
Landsteinerstr. 5 
D-63303 Dreieich 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/09/600/001 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
Medicinal product subject to medical prescription. 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Zutectra 500 IU 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: {number} [product code] 
SN: {number} [serial number] 
NN: {number} [national reimbursement number or other national number identifying the medicinal 
product] 
 



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MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS 
 
BLISTER 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Zutectra 500 IU injection 
Human hepatitis B immunoglobulin 
Subcutaneous use 
 
 
2. NAME OF THE MARKETING AUTHORISATION HOLDER 
 
Biotest Pharma GmbH 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. OTHER 
 
 
 



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MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Zutectra 500 IU injection 
Human hepatitis B immunoglobulin 
 
 
2. METHOD OF ADMINISTRATION 
 
Subcutaneous use 
 
 
3. EXPIRY DATE 
 
EXP  
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
500 IU  
 
 
6. OTHER 
 
  



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B. PACKAGE LEAFLET 
 



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Package leaflet: Information for the user 
 

Zutectra 500 IU solution for injection in pre-filled syringe 
Human hepatitis B 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 pharmacist. 
- 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 doctor or pharmacist. This includes any possible side 

effects not listed in this leaflet. See section 4. 
 
What is in this leaflet: 
 
1. What Zutectra is and what it is used for 
2. What you need to know before you use Zutectra 
3. How to use Zutectra 
4. Possible side effects 
5. How to store Zutectra 
6. Contents of the pack and other information 
7. How to inject Zutectra by yourself or by caregiver 
 
 
1. What Zutectra is and what it is used for 
 
What Zutectra is 
 
Zutectra contains antibodies against the hepatitis B virus which are the body's own defensive 
substances to protect you from hepatitis B. Hepatitis B is an inflammation of the liver caused by the 
hepatitis B virus. 
 
What Zutectra is used for 
 
Zutectra is used to prevent re-infection of hepatitis B in adults who have had a liver transplant at least 
1 week ago because they had liver failure caused by hepatitis B. 
 
 
2. What you need to know before you use Zutectra  
 
Do not use Zutectra 
- if you are allergic to human immunoglobulin or any of the other ingredients of this medicine (listed 

in section 6).  
An allergic reaction may include sudden wheeziness, difficulty in breathing, fast pulse, swelling of the 
eyelids, face, lips, throat or tongue, rash or itching.  
 
Zutectra is for subcutaneous (under the skin) injection only. Injection into a vein or a blood vessel may 
result in allergic shock. 
 
Warnings and precautions 
 
Please tell your doctor or healthcare professional prior to treatment  
- if you have been told that you have antibodies against immunoglobulins of the type IgA in your 

blood. This is very rare and may result in allergic reactions. 
 



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You may be allergic to immunoglobulins (antibodies) without knowing it, even if you have tolerated 
previous treatments with human immunoglobulins. Particularly if you do not have enough 
immunoglobulins of the type IgA in your blood, allergic reactions such as a sudden fall in blood 
pressure or shock may occur.  
 
You will be carefully observed during and shortly after the 1st injection with Zutectra to make 
sure that you do not suffer from a reaction. If you have an allergic reaction to Zutectra, the injection 
will be stopped immediately. Please tell your doctor or healthcare professional immediately if you 
notice any reactions during your injection with Zutectra. 
 
If you are HBs antigen positive you will not receive Zutectra since there is no benefit in 
administering this medicine to you. Your doctor will be able to explain this to you. 
 
For your own safety you will be monitored for antibody levels regularly. 
 
Possible interference with blood tests 
Zutectra might affect the results of certain blood tests (serological tests). Please tell your doctor about 
your treatment with Zutectra prior to any blood test. 
 
Information on the starting material of Zutectra and the possibility of transmission of infectious 
agents: 
 
The starting material or what Zutectra is made from is 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. 
 
The measures taken are considered effective for enveloped viruses such as human immunodeficiency 
virus (HIV), hepatitis B virus and hepatitis C virus, and for the non-enveloped hepatitis A virus. The 
measures taken may be of limited value against non-enveloped viruses such as parvovirus B19 virus 
(causative agent of Ringel rubella). 
 
Immunoglobulins like Zutectra have not been associated with hepatitis A or parvovirus B19 infections 
possibly because the antibodies against these infections, which are contained in the product, are 
protective. 
 
It is strongly recommended that every time Zutectra is used (both at hospital or in a home treatment), 
the name and batch number of the medicine are recorded in order to maintain a record of the 
batches used. 
 
Other medicines and Zutectra 
Tell your doctor or healthcare professional if you are taking, have recently taken or might take any 
other medicines. 
 
Vaccinations 
 
Zutectra can reduce the effectiveness of some vaccines (measles, rubella, mumps, chicken pox) for a 
period of up to 3 months. 



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You may have to wait at least 3 months after the last injection of Zutectra before you can have live 
attenuated vaccines. 
 
Please tell your doctor about your treatment with Zutectra prior to any vaccination. 
 
Pregnancy, breast-feeding and fertility 
If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask 
your doctor or healthcare professional for advice before taking this medicine. 
 
Driving and using machines 
Zutectra has no or negligible effects on your ability to drive or use machines. 
 
 
3. How to use Zutectra 
 
Zutectra is intended for subcutaneous (under the skin) injection. The contents of one syringe are 
intended for use once only. Do not inject into a blood vessel. 
 
In most cases you will be given the injection by your doctor or nurse. However, if your antibody levels 
are sufficient and you have a fixed dose regimen, you or your caregiver may be trained to carry out the 
injection at home (see below).  
 
For the documentation of your injections of Zutectra it is strongly recommended to use the treatment 
diary. Your doctor will explain you how to use it. 
 
The dose can be individually established and adapted from 500 IU up to 1,000 IU (in exceptional cases 
up to 1,500 IU) weekly or fortnightly. The dose will depend on your condition. Your doctor will 
regularly check your condition and tell you how much and how often you need to use Zutectra. 
 
Injecting by yourself or by caregiver 
You can inject Zutectra yourself without the help of your doctor, if they have trained you to do this. If 
you are administering Zutectra yourself, please read instructions in the section “How to inject 
Zutectra by yourself or by caregiver” carefully. 
 
Zutectra must be brought to room temperature (approx. 23°C-27°C) before use. 
 
If you use more Zutectra than you should 
Consequences of an overdose are not known. However, if you have used more than the prescribed 
dose of Zutectra, contact your doctor, healthcare professional or pharmacist straight away for advice.  
 
If you forget to use Zutectra 
Do not take a double dose to make up for a forgotten injection. Talk to your doctor about managing 
the dose. Your doctor will tell you how much and how often you need to use Zutectra. 
 
Make sure you use Zutectra as prescribed and as instructed by your doctor to avoid the risk of a 
hepatitis B re-infection. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Most side effects observed with Zutectra were mild to moderate in nature.  In very rare cases human 
normal immunoglobulins may cause a serious allergic reaction. 
 



22 

If you notice any of the following effects stop the injection and tell your doctor immediately: 
- rash, 
- itching, 
- wheezing,  
- difficulty in breathing, 
- swelling of the eyelids, face, lips, throat or tongue, 
- low blood pressure, fast pulse 
 
This can be an allergic reaction or a serious allergic reaction (anaphylactic shock). 
 
In case of any adverse event after the injection speak to your doctor immediately. 
 
The following side effects have been reported with Zutectra: 
 
Common (may affect up to 1 in 10 people): 

- injection site reactions: pain, hives (urticaria) at injection site, haematoma (a collection of 
blood in tissue under the skin), reddening of the skin (erythema). 

 
Uncommon (may affect up to 1 in 100 people): 
- headache  
- upper abdominal pain (from your chest to the belly button) 
 
Furthermore the following reactions have been reported once only: 
- tiredness (fatigue) 
- high blood pressure (hypertension) 
- inflammation of the nose and throat (nasopharyngitis) 
- muscle spasm 
- allergic reactions (hypersensitivity) 
- abnormal heartbeat (palpitations), cardiac discomfort 
- itching (pruritus), rash 
- pain in the mouth and throat 
 
With other human immunoglobulin preparations the following additional symptoms have been 
reported:  
- chills 
- headache 
- dizziness 
- fever 
- vomiting 
- mild allergic reactions 
- nausea (urge to vomit) 
- joint pain 
- low blood pressure 
- moderate low back pain 
- injection site reactions: swelling, soreness, redness, hardening of the skin, local heat, itching, 

bruising and rash. 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, healthcare professional or pharmacist. 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 Zutectra 



23 

 
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 syringe label 
after EXP. 
 
Store and transport refrigerated (2°C-8°C).  Do not freeze. Keep the container in the outer carton in 
order to protect from light. 
 
The solution should be administered immediately after opening the syringe. 
 
Do not use Zutectra if you notice that the solution is cloudy or has particles. 
 
Any unused medicine or waste material should be disposed of in accordance with local requirements.  
Once the injection has been completed, dispose of all needles, syringes and empty glass containers 
without delay in a container intended for sharp objects you were provided with. 
 
 
6. Contents of the pack and other information 
 
What Zutectra contains 
 
- The active substance is human hepatitis B immunoglobulin 500 IU/ml. 
- Zutectra contains 150 mg/ml of human plasma protein of which at least 96 % is 

immunoglobulin G (IgG). The maximum immunoglobulin A (IgA) content is 
6,000 micrograms/ml. 

- The other ingredients are glycine and water for injections. 
 
What Zutectra looks like and the contents of the pack 
 
Zutectra is presented as a solution for injection provided in pre-filled syringes (500 IU/ml - pack size 
of 5 in a blister). The colour of the solution can vary from clear to pale yellow or light brown. 
 
One pre-filled syringe of 1 ml Zutectra contains 500 IU. Zutectra is supplied in a pack size containing 
5 pre-filled syringes each in a blister pack.  
 
Marketing Authorisation Holder and Manufacturer 
 
Biotest Pharma GmbH 
Landsteinerstrasse 5 
D-63303 Dreieich 
Germany 
Tel.: + 49 6103 801-0 
Fax: + 49 6103 801-150 
Email: mail@biotest.com 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Infarama BVBA 
Stationsstraat 27 
B-3570 Alken 
Tél/Tel: +32 11 31 26 16 
 

Lietuva 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Tel: + 49 6103 801-0 
 



24 

България 
МЕДИС ФАРМА БЪЛГАРИЯ ЕООД 
1700 София 
Ул. Проф. Атанас Иширков 31, офис 6 
T: +359 2 427 49 58 
 

Luxembourg/Luxemburg 
Biotest AG 
Landsteinerstr. 5 
D-63303 Dreieich 
Tél/Tel: + 49 6103 801-0 
 

Česká republika 
Reg-Pharm spol.s.r.o. 
Fialková 45 
CZ-10600 Praha 10 
Tel: + 420 2 7265 4004 
 

Magyarország 
Biotest Hungaria Kft. 
Torbágy u. 15/A 
H-2045 Törökbálint 
Tel.: + 36 23 511 311 
 

Danmark 
Unimedic Pharma AB 
Box 6216 
SE-102 34 Stockholm 
Tlf:+ 46 10 130 99 80 
 

Malta 
Rodel Ltd 
55, Ravina 
Triq ir-Russett 
MT-Kappara SGN 4432 
Tel: + 356 27 386221 
 

Deutschland 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Tel: + 49 6103 801-0 
 

Nederland 
Infarama BVBA 
Stationsstraat 27 
B-3570 Alken 
Tel: +32 11 31 26 16 
 

Eesti 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Tel: + 49 6103 801-0 
 

Norge 
Unimedic Pharma AB 
Box 6216 
SE-102 34 Stockholm 
Tlf:+ 46 10 130 99 80 
 
 

Ελλάδα 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Τηλ: + 49 6103 801-0 
 

Österreich 
Biotest Austria GmbH 
Einsiedlergasse 58 
A-1050 Wien 
Tel: + 43 1 545 15 61-0 
 

España 
Biotest Medical, S.L.U. 
C/Frederic Mompou, 
5 – 6° 3a A 
ES-08960 Sant Just Desvern Barcelona 
Tel: + 34 935 952 661 
 

Polska 
Nobipharm Sp. Z.o.o. 
ul Rydygiera 8 
PL–01-793 Warszawa 
Tel.: + 48 22 8322638 
 

France 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Tél: 00800 98832872 
 

Portugal 
SPCare Especialidades Farmacêuticas, Lda 
Rua Luciano Cordeiro, nº 123, 1º dto. 
PT-1050 139 Lisboa 
Tel: + 351 21 193 14 20 
 



25 

Hrvatska 
Medis Adria d.o.o. 
Kolarova 7, 
10000 Zagreb 
T: +385 1 2303 446 
 

România 
Besmax Pharmaceutical Distribution S.R.L. 
61A Drumul Plaiul Sarului Street, Room 5 
013982 Bucharest, District 1 – RO 
Tel: + 40 743 207 205  
 

Ireland 
Aquilant Pharmaceuticals 
21 Fonthill Business Park 
Fonthill Road 
Clondalkin 
Dublin 22 
Ireland 
Tel: + 353 1 404 8344 
 

Slovenija 
MEDIS, d.o.o.  
Brnčičeva 1,  
1231 Ljubljana-Črnuče,  
Slovenia 
Tel: +386 1 589 69 00 
 

Ísland 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Sími: + 49 6103 801-0 
 

Slovenská republika 
Reg-Pharm spol.s.r.o. 
Fialková 45 
CZ-10600 Praha 10 
Tel: + 420 2 7265 4004 
 

Italia 
Biotest Italia S.r.l. 
Via Leonardo da Vinci 43 
I-20090 Trezzano sul Naviglio 
Tel: + 39 02 4844 2951 
 

Suomi/Finland 
Unimedic Pharma AB 
Box 6216 
SE-102 34 Stockholm 
Puh/Tel: + 46 10 130 99 80 
 

Κύπρος 
ΑΚΗΣ ΠΑΝΑΓΙΩΤΟΥ & ΥΙΟΣ ΛΤΔ 
Γ. ΚΡΑΝΙΔΙΩΤΗ 
Τ. Θ. 22578 1522 ΛΕΥΚΩΣΙΑ 
Κ Υ Π Ρ Ο Σ 
Τηλ: + 357 22 611 038 
 

Sverige 
Unimedic Pharma AB 
Box 6216 
SE-102 34 Stockholm 
Tel: + 46 10 130 99 80 
 

Latvija 
Biotest AG 
Landsteinerstrasse 5 
D-63303 Dreieich 
Tel: + 49 6103 801-0 
 

United Kingdom 
Biotest (UK) Ltd. 
First Floor, Park Point, 17 High Street, 
Longbridge 
Birmingham B31 2UQ –UK 
Tel: + 44 121 733 3393 
 

 
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. 
 
 
7. How to inject Zutectra by yourself or by caregiver 
 
The following instructions are intended to explain how to inject Zutectra. Please read the instructions 
carefully and follow them step by step. The doctor or his/her assistant will teach you the process of 
administration. 
 
Do not attempt to inject Zutectra until you are sure that you understand how to prepare the injection 
solution and give the injection. 



26 

 
General information:  
- Keep the syringes and syringe disposal unit out of the reach of children; lock the supplies if 

possible. 
- Try to take the injection at the same time of day. This makes it easier to remember it. 
- Always double-check the dose. 
- The solution must be brought to room temperature before use. 
- Open each syringe only when you are ready for an injection. You should administer the 

injection immediately after opening the syringe. 
- The colour of the solution can vary from clear to pale yellow up to light brown. Do not use 

solutions that are cloudy or have particles. 
- This medicine must not be mixed with other medicines. 
 
Before the injection: 
 
1. Wash your hands. It is important to have your hands and the items you use as clean as possible. 
 
2. Lay out everything you need in advance. Find a clean place where you can spread out all the items 
you are going to use: 
 
- two alcohol swabs, 
- one syringe of Zutectra, 
- one needle suitable for subcutaneous injection. 
 
Please note that alcohol swabs and needles are not contained in the pack and you need to supply them 
yourself. 
 
3. Before preparing the injection, decide where you are going to inject. You should inject Zutectra into 
the fatty layer between the skin and muscle (about 8 to 12 mm under the skin). The best places for 
injections are where the skin is loose and soft for example in the abdomen, arm, thigh or buttocks, and 
away from joints, nerves, bones.  
 
Important: Do not use on any area where you can feel lumps, bumps, firm knots, pain or on an area 
that is discoloured, indented, scabbed, or where the skin is broken. Talk to the doctor or healthcare 
professional about these or any other unusual conditions you may find. You should rotate the injection 
site at every injection. If some areas are too difficult for you to reach, you may need a caregiver to 
help you with these injections. 
 
4. Prepare the Zutectra syringe:  
 

  
 

 
- Take the syringe out of the pack. 
- Examine the solution carefully. It should be clear 

and contain no particles. If the solution is 
discoloured, cloudy or contains particles, discard 
it and start again with a new syringe. 

- Remove the protective cap from the syringe. 
 

  
 

 
- Take the needle out of its sterile pack and fit the 

needle onto the syringe. 

 



27 

5. Get rid of any air bubbles that may be in the syringe. 
 

 
 

 
- Hold the syringe with the needle pointing 

upwards, and tap the syringe gently with your 
fingers until the air has collected at the tip. 
Carefully push the plunger in until the air bubbles 
have disappeared. 

 
Injection 
 
1. Choose the area where you will make the injection and make a note of it in the diary. 
 

 

Abdomen (stomach): Do not use the area within 
one inch around the navel. Avoid using the belt 
line area, as rubbing may irritate the injection site. 
Avoid surgical scars. This is likely to be the easiest 
place to inject if you are doing it yourself. 

Thighs: Use middle and outer areas where you can 
pinch up tissue. You are likely to have more fatty 
tissue the closer you are to the hip and the further 
you are from the knee. 

Arms: The back of the upper arm should be used. It 
is hard to pinch up the tissue and inject Zutectra 
yourself using this site. If you do choose to inject 
your arm yourself, try to pinch up the tissue by 
placing your upper arm over the back of a chair or 
brace it against a wall. It is much easier for 
someone else to use this site if you do need help. 

Buttocks: Use any area where you can pinch up 
tissue. It’s harder to give yourself an injection 
here. Try standing in front of a mirror to locate the 
site or you may want to ask your caregiver to give 
you the injection. 

 
It's important to change (rotate) the injection sites. This will help the skin stay supple and help the 
medicine be absorbed evenly. Rotating sites means starting at one site and using all other sites before 
going back to the first site you used. Then start the rotation again. It may be helpful to keep a record of 
where you had the last injection to avoid problems. 
 
The administration in thighs is shown as an example in the following pictures: 
 

  
2. Wipe the intended area with an alcohol swab. Let 
the skin air-dry. 

 

  
 

 
3. Gently pinch the skin together around the 
disinfected injection site (to raise it up a little) and 
push the needle into the skin with a rapid, confident 
movement at an angle of 45 to 90 degrees. Inject 



28 

beneath the skin as you have been shown by the 
doctor or nurse.  
 

  
 

 
4. Inject the liquid by pressing gently on the plunger. 
Allow yourself enough time to inject the whole of the 
solution until the syringe is empty. 

  
 

 
5. Then pull the needle out immediately and let go of 
the pinched skin. 

  
 

 
6. Clean the injection site by wiping it in a circular 
motion with the alcohol swab. 
 
 

 
Dispose of all used items 
 
Once the injection has been completed, dispose of all needles and empty glass containers without 
delay in a container intended for sharp objects. 
 


	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