Igantibe

Package leaflet: Information for the patient

IGANTIBE 600 UI/3 ml solution for injection for intramuscular use, 1000 UI/5 ml solution for injection for intramuscular use

Human hepatitis B immunoglobulin
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What Igantibe is and what it is used for

Igantibe is an injectable solution of human anti-hepatitis B immunoglobulins, which are specific antibodies directed against the surface antigen of the hepatitis B virus.
The medicine belongs to the pharmacotherapeutic group: immune sera and immunoglobulins.
Administration of Igantibe is indicated for:
Hepatitis B immunoprophylaxis.

• In case of accidental exposure in non-immunized individuals (including those with incomplete or unknown vaccination status).
• In patients on hemodialysis, until vaccination becomes effective.
• In newborns of mothers who are carriers of the hepatitis B virus.
• In individuals who have not shown an immune response (non-detectable anti-hepatitis B antibodies) after vaccination and who require ongoing prevention due to persistent risk of infection with the hepatitis B virus.

Maintenance prophylaxis of hepatitis B recurrence after liver transplantation in liver failure caused by hepatitis B.

2. What you need to know before using Igantibe

Do not use Igantibe

• If you are allergic (hypersensitive) to human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Igantibe.

• Make sure that Igantibe is not administered into a blood vessel, as this may cause shock.
• If you are a carrier of HBsAg, you will not benefit from administration of this product.
• True hypersensitivity reactions are rare.
• Igantibe contains small amounts of IgA. If you are IgA-deficient, you may develop antibodies against IgA and may experience anaphylactic reactions after administration of blood components containing IgA. Your doctor will assess the benefit of treatment with Igantibe against the potential risk of hypersensitivity reactions.
• Rarely, human anti-hepatitis B immunoglobulin may cause a drop in blood pressure associated with an anaphylactic reaction, even in patients who have previously tolerated treatment with human immunoglobulin well.
• If symptoms of allergic or anaphylactic-type reactions occur, your doctor will immediately stop administration of the medicine and initiate standard treatment for shock.

Viral safety
When medicines are manufactured from human blood or plasma, special safety measures are applied to prevent transmission of infectious agents to patients. These measures include:

• Careful selection of blood and plasma donors to ensure that potential carriers of infections are excluded,
• Testing of each donation and plasma pool to detect the presence of viruses/infections,
• Inclusion of procedures during blood or plasma processing that can inactivate or remove viruses.

Despite these measures, when medicines derived from human blood or plasma are administered, the possibility of transmitting infections cannot be completely ruled out. This also applies to viruses of unknown or emerging nature or other types of infections.
The measures adopted are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as against the non-lipid-enveloped hepatitis A virus (HAV). However, the effectiveness of these measures may be limited against non-lipid-enveloped viruses such as parvovirus B19.
Transmission of hepatitis A or parvovirus B19 infections has not been associated with immunoglobulins, probably because antibodies against these infections contained in the product provide a protective effect.
It is strongly recommended that whenever Igantibe is administered, the name and batch number of the product be recorded to ensure traceability between the patient and the product batch used.

Children and adolescents
The same warnings mentioned for adults are expected to apply to the pediatric population.

Other medicines and Igantibe
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

Interference with vaccinations (live attenuated viruses)
Administration of Igantibe may reduce the efficacy of certain live attenuated virus vaccines, such as measles, mumps, rubella, and varicella vaccines, for up to 3 months. At least 3 months should elapse after administration of Igantibe before vaccination with these vaccines. In the case of measles vaccination, this reduction in efficacy may last up to one year. Therefore, if you receive the measles vaccine, you should undergo periodic monitoring of antibody levels.
Human anti-hepatitis B immunoglobulin should be administered 3–4 weeks after vaccination with a live attenuated virus vaccine; if administration of human anti-hepatitis B immunoglobulin is required within 3–4 weeks after vaccination with a live attenuated virus, the vaccination should be repeated 3 months after administration of anti-hepatitis B immunoglobulin.

Interference with blood tests
Inform your doctor or nurse if you are undergoing blood tests after receiving Igantibe.
After administration of immunoglobulins, a transient increase in various passively transferred antibodies in your blood may occur, which could lead to altered laboratory test results (false positive results).
Passive transfer of antibodies against erythrocyte antigens (e.g., A, B, D) may interfere with certain serological tests for erythrocyte antibodies, such as the antiglobulin test (Coombs test).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
The safety of this medicine during pregnancy has not been demonstrated in controlled clinical studies. Clinical experience with immunoglobulins suggests that harmful effects on pregnancy, the fetus, or the newborn are unlikely.
Immunoglobulins are excreted in breast milk, thereby contributing to antibody transfer to the newborn.
Clinical experience with human immunoglobulins suggests that harmful effects on fertility are unlikely.

Driving and operating machinery
No effects related to the influence of Igantibe on the ability to drive vehicles or operate machinery have been observed.

Igantibe contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., it is practically "sodium-free".

3. How to use Igantibe

Use this medicine exactly as instructed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Igantibe must be administered exclusively by intramuscular injection.
If a high dose is required (> 2 ml in children or > 5 ml in adults), it is recommended to
divide the dose and administer it at different anatomical sites.
If vaccination needs to be given at the same time, the immunoglobulin and the vaccine
must be administered at two different anatomical sites.
If intramuscular administration is contraindicated (e.g. due to coagulation disorders), you will be
treated with alternative products.
The medicine should be brought to room temperature or body temperature before administration.
The solution should be clear or slightly opalescent and may show a small amount of particulate
matter during storage. The solution should be inspected visually before administration for the
presence of particulate matter or any change in colour. Do not use solutions that appear cloudy or
contain deposits.
After injection, firm manual pressure should be applied with a gauze pad at the injection site.
Igantibe must not be mixed with other medicines.
Your doctor will determine the appropriate dose for you.
 Prevention of hepatitis B following accidental exposure in non-immunized individuals:
at least 500 IU, depending on the extent of exposure, as soon as possible and preferably within
24–72 hours.
 Immunoprophylaxis of hepatitis B in patients undergoing haemodialysis:
8–12 IU/kg up to a maximum of 500 IU, every 2 months until seroconversion following
vaccination occurs.
 Prevention of hepatitis B in newborns of hepatitis B virus carrier mothers, at birth or as soon as
possible after birth:
30–100 IU/kg. Repeated administration of hepatitis B immunoglobulins may be necessary until
seroconversion following vaccination occurs.
In all these situations, vaccination against hepatitis B virus is strongly recommended. The first dose of
vaccine may be administered on the same day as human hepatitis B immunoglobulin, but at different
anatomical sites.
In individuals who do not show an immune response (non-detectable hepatitis B antibodies) after
vaccination and for whom ongoing prevention is required, administration of 500 IU every 2 months
in adults and 8 IU/kg in children may be considered;
10 IU/ml is considered the minimum protective antibody titre.
 Maintenance prophylaxis to prevent recurrence of hepatitis B after liver transplantation in
hepatitis B-induced liver failure:
2000 IU every 15 days, or until an anti-hepatitis B antibody titre greater than 250 IU/l is achieved
during the first 3 months post-transplantation, and greater than 100 IU/l thereafter.
Use in children and adolescents
There are no available data on the prevention of hepatitis B following accidental exposure in
non-immunized individuals, immunoprophylaxis of hepatitis B in patients undergoing haemodialysis,
or maintenance prophylaxis to prevent recurrence of hepatitis B after liver transplantation. For the
prevention of hepatitis B in newborns of hepatitis B virus carrier mothers, see information above.
If you use more Igantibe than you should
The consequences of overdose are unknown.
If you use more Igantibe than you should, inform your doctor or pharmacist immediately.
If you forget to use Igantibe
Do not use a double dose to make up for the missed dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
As with all normal human immunoglobulins administered intramuscularly, the following reactions may occur:

Occasionally:

• Chills
• Fever
• Headache
• Nausea
• Vomiting
• Allergic reactions
• Joint pain
• Decrease in blood pressure (hypotension)
• Moderate back pain (lumbago)

Rarely, normal human immunoglobulin may cause a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even when no allergic reaction (hypersensitivity) was observed during previous administrations.

At the injection site, local reactions may frequently occur: swelling, tenderness, redness, induration, local warmth, itching, and skin rash.

Post-marketing experience with the use of Igantibe has reported the following adverse reactions: hypersensitivity, excessive lacrimation, nausea, skin flushing, rash, urticaria, erythema, and injection site pain. The frequency of these reactions is "not known".

In a clinical study, administration of Igantibe resulted in increased serum levels of alanine-aminotransferase (ALT), a liver enzyme.

For information on safety regarding the possible transmission of infections, see section 2, “What you need to know before using Igantibe”.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via
http://www.agenziafarmaco.gov.it/it/responsabili . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Igantibe

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word
"Exp." The expiry date refers to the last day of the month indicated.
The expiry date applies to the product in its original, undamaged packaging and stored as recommended.
Store in a refrigerator (2 °C-8 °C) in the original packaging. Do not freeze.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Igantibe contains

• The active substance is: human hepatitis B immunoglobulin.

One vial of Igantibe contains:
600 UI/3 ml 1000 UI/5 ml
Human hepatitis B immunoglobulin 600 IU 1000 IU
(200 IU/ml) (200 IU/ml)
Human proteins 160 g/l 160 g/l
of which human G immunoglobulins (IgG)
not less than 95% 95%
The IgA content is less than 1 mg/ml.

• The other components are: glycine, sodium chloride, and water for injections.

(See section 2. “What you need to know before using Igantibe” for further information on excipients).

Description of the appearance of Igantibe and package contents
Igantibe is an injectable solution. The solution may vary in color from colorless to pale yellow/light brown. During storage, it may appear slightly opalescent or show the presence of a small amount of particulate matter.
Packaging:
Igantibe 600 IU/3 ml solution for injection for intramuscular use: 1 vial of 3 ml
Igantibe 1000 IU/5 ml solution for injection for intramuscular use: 1 vial of 5 ml

Marketing Authorization Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN

Patient information leaflet

Igantibe 200 UI/mL solution for injection in a pre-filled syringe for intramuscular use

Human hepatitis B immunoglobulin
Please read this leaflet carefully before using this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What Igantibe is and what it is used for

Igantibe is a ready-to-use prefilled syringe injectable solution of human anti-hepatitis B immunoglobulins,
which are specific antibodies directed against the hepatitis B virus surface antigen.
This medicinal product belongs to the pharmacotherapeutic group: immune sera and immunoglobulins.
Administration of Igantibe is indicated for:
Hepatitis B immunoprophylaxis.

• In case of accidental exposure in non-immunized individuals (including those with incomplete or unknown vaccination status).
• In patients undergoing hemodialysis, until vaccination becomes effective.
• In newborns of mothers who are carriers of hepatitis B virus.
• In individuals who have not shown an immune response (undetectable anti-hepatitis B antibodies) after vaccination and who require ongoing prevention due to persistent risk of infection with hepatitis B virus.

Prophylaxis to prevent recurrence of hepatitis B after liver transplantation in liver failure caused by hepatitis B.

2. What you need to know before using Igantibe

Do not use Igantibe

• if you are allergic (hypersensitive) to human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6).

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before using Igantibe.

• Make sure that Igantibe is not administered into a blood vessel, as this may cause shock.
• If you are a carrier of HBsAg, you will not benefit from administration of this product.
• True hypersensitivity reactions are rare.
• Igantibe contains small amounts of IgA. If you are IgA-deficient, you may develop antibodies against IgA and may experience anaphylactic reactions after administration of blood components containing IgA. Your doctor will assess the benefit of treatment with Igantibe against the potential risk of hypersensitivity reactions.
• Rarely, human anti-hepatitis B immunoglobulin may induce a drop in blood pressure associated with an anaphylactic reaction, even in patients who have previously tolerated treatment with human immunoglobulin well.
• If symptoms of allergic or anaphylactic reactions occur, your doctor will immediately stop administration of the medicine and you will be given standard treatment for shock.

Viral safety
When medicines are produced from human blood or plasma, special safety measures are applied to prevent transmission of infectious agents to patients. These measures include:

• Careful selection of blood and plasma donors to ensure that potential carriers of infections are excluded,
• Testing of each donation and plasma pool to detect the presence of viruses/infections,
• Inclusion of processing procedures capable of inactivating or removing viruses during blood or plasma manufacturing.

Despite these measures, when medicines derived from human blood or plasma are administered, the possibility of transmitting infections cannot be completely ruled out. This also applies to unknown or emerging viruses or other types of infections.
The measures taken are considered effective against lipid-enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and against the non-enveloped hepatitis A virus (HAV). However, the effectiveness of these measures may be limited against non-enveloped viruses such as parvovirus B19.
Immunoglobulins have not been associated with transmission of hepatitis A or parvovirus B19 infections, probably because antibodies against these infections present in the product provide a protective effect.
It is strongly recommended that each time Igantibe is administered, the name and batch number of the product be recorded, in order to maintain traceability between the patient and the batch of product used.

Children and adolescents
The same warnings mentioned for adults are expected to apply to the pediatric population.

Other medicines and Igantibe
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those not requiring a prescription.

Interference with vaccinations (live attenuated viruses)
Administration of Igantibe may reduce the effectiveness of certain live attenuated virus vaccines, such as measles, mumps, rubella, and varicella vaccines, for up to 3 months. At least 3 months should elapse after administration of Igantibe before these vaccines are given. In the case of measles vaccination, this reduction in effectiveness may last up to one year. Therefore, if you receive the measles vaccine, you should undergo periodic monitoring of antibody levels.
Human anti-hepatitis B immunoglobulin should be administered 3–4 weeks after vaccination with a live attenuated virus vaccine. If administration of human anti-hepatitis B immunoglobulin is required within 3–4 weeks after vaccination with a live attenuated virus, the vaccination should be repeated 3 months after administration of anti-hepatitis B immunoglobulin.

Interference with blood tests
Inform your doctor or nurse if you are undergoing blood tests after receiving Igantibe.
After administration of immunoglobulins, a transient increase in various passively transmitted antibodies in your blood may occur, which could lead to altered laboratory test results (false positive results).
Passive transmission of antibodies against erythrocyte antigens (e.g., A, B, D) may interfere with certain serological tests for erythrocyte antibodies, such as the antiglobulin test (Coombs test).

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
The safety of this medicine during pregnancy has not been demonstrated in controlled clinical studies. Clinical experience with immunoglobulins suggests that harmful effects on the course of pregnancy, the fetus, or the newborn are unlikely.
Immunoglobulins are excreted in breast milk, thereby contributing to the transfer of antibodies to the newborn.
Clinical experience with human immunoglobulins suggests that harmful effects on fertility are unlikely.

Driving and using machines
No effects on the ability to drive vehicles or operate machinery have been observed with Igantibe.

Igantibe contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e., essentially “sodium-free”.

3. How to use Igantibe

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Igantibe must be administered exclusively by intramuscular injection.
If a high dose is required (> 2 ml in children or > 5 ml in adults), it is recommended to divide the dose and administer it at different anatomical sites.
If vaccination needs to be administered at the same time, the immunoglobulin and the vaccine must be given at two different anatomical sites.
If intramuscular administration is contraindicated (e.g. due to coagulation disorders), you will be treated with alternative products.
The medicine should be brought to room temperature or body temperature before administration.
The solution should be clear or slightly opalescent and may show a small amount of particulate matter during storage. The solution should be visually inspected before administration for the presence of particulate matter or discoloration. Do not use solutions that appear cloudy or contain deposits.
After injection, firm manual pressure should be applied using a gauze pad at the injection site.
Igantibe must not be mixed with other medicines.
Your doctor will determine the appropriate dose for you.

• Prevention of hepatitis B following accidental exposure in non-immunized individuals:
  At least 500 IU, depending on the extent of exposure, as soon as possible and preferably within 24–72 hours.

• Immunoprophylaxis of hepatitis B in patients undergoing haemodialysis:
  8–12 IU/kg up to a maximum of 500 IU, every 2 months until seroconversion following vaccination occurs.

• Prevention of hepatitis B in newborns of mothers who are hepatitis B virus carriers, at birth or as soon as possible after birth:
  30–100 IU/kg. Repeated administration of hepatitis B immunoglobulins may be necessary until seroconversion following vaccination occurs.

In all these situations, vaccination against hepatitis B virus is strongly recommended. The first dose of vaccine may be administered on the same day as human hepatitis B immunoglobulin, but at different anatomical sites.

In individuals who have not shown an immune response (non-detectable hepatitis B antibodies) after vaccination and for whom ongoing prevention is required, administration of 500 IU every 2 months in adults and 8 IU/kg in children may be considered; a level of 10 IU/ml is considered the minimum protective antibody titre.

• Maintenance prophylaxis to prevent recurrence of hepatitis B after liver transplantation in liver failure caused by hepatitis B:
  2000 IU every 15 days, or until achieving a hepatitis B antibody titre greater than 250 IU/l within the first 3 months post-transplantation, and greater than 100 IU/l thereafter.

Instructions for preparation and administration of the medicine

1. Open the plastic container containing the syringe, plunger, and needle.
2. Ensure the syringe is at room temperature (20–25 °C) before use.
3. Separate the syringe and plunger from the plastic holder.
4. Attach the plunger to the base of the syringe. Rotate the plunger rod clockwise until it reaches the end of the thread to secure it.
5. Hold the syringe firmly, with the cap at the end facing upwards, where the needle will be attached. Remove the cap and connect the needle to the syringe.
6. Prepare the patient's injection site.
7. Remove the needle cover (perform this step only immediately before injection), expel any air, and insert the needle into the selected site. Aspirate before injection to ensure the needle is not in a blood vessel. Inject the product intramuscularly.

Use in children and adolescents
No data are available for the prevention of hepatitis B following accidental exposure in non-immunized individuals, for immunoprophylaxis of hepatitis B in patients undergoing haemodialysis, or for maintenance prophylaxis of hepatitis B recurrence after liver transplantation. For prevention of hepatitis B in newborns of mothers who are hepatitis B virus carriers, see information above.

If you use more Igantibe than you should
The consequences of overdose are unknown.
If you use more Igantibe than you should, inform your doctor or pharmacist immediately.

If you forget to use Igantibe
Do not use a double dose to make up for the forgotten dose.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
As with all normal human immunoglobulins administered intramuscularly, the following reactions may occur:
Occasionally:

• Chills
• Fever
• Headache
• Nausea
• Vomiting
• Allergic reactions
• Joint pain
• Decrease in blood pressure (hypotension)
• Moderate back pain (lumbago)

Rarely, normal human immunoglobulin may cause a sudden drop in blood pressure and, in isolated cases, anaphylactic shock, even when no allergic reaction (hypersensitivity) occurred during previous administrations.
At the injection site, local reactions may frequently occur: swelling, tenderness, redness, induration, local warmth, itching, and skin rash.
From post-marketing experience with the use of Igantibe, the following adverse reactions have been reported: hypersensitivity, excessive lacrimation, nausea, skin flushing, skin rash, urticaria, erythema, and injection site pain. The frequency of these reactions is "not known".
In a clinical study, administration of Igantibe resulted in increased serum levels of alanine-aminotransferase (ALT), a liver enzyme.
For information on safety regarding the potential transmission of infections, see section 2. “What you need to know before using Igantibe”.
Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You may also report side effects directly via
https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Igantibe

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after the word
Exp. The expiry date refers to the last day of that month.
The expiry date applies to the product in its original sealed packaging stored as recommended.
Store in a refrigerator (2 °C-8 °C) in the original packaging. Do not freeze.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Igantibe contains

• The active substance is human anti-hepatitis B immunoglobulin. A pre-filled syringe of Igantibe contains:

600 UI/3 mL 1 000 UI/5 mL
Human anti-hepatitis B immunoglobulin 600 UI 1 000 UI
(200 UI/mL) (200 UI/mL)
Human proteins 160 g/L 160 g/L
of which human G immunoglobulins (IgG)
not less than 95% 95%
The IgA content is less than 1 mg/mL.

• The other components are glycine, sodium chloride, and water for injections.

(See section 2. “What you need to know before using Igantibe” for further information on
excipients).

Description of the appearance of Igantibe and package contents
Igantibe is an injectable solution in a pre-filled syringe. The solution may vary in colour from colourless to pale yellow/light brown. During storage, it may appear slightly opalescent or show the presence of a small amount of particulate matter.

Packaging:
3 mL or 5 mL solution in pre-filled syringe (Type I glass), with chlorobutyl rubber stoppers at the front and rear.
One pre-filled syringe containing 600 UI in 3 mL of injectable solution.
One pre-filled syringe containing 1 000 UI in 5 mL of injectable solution.
Each package also contains a sterile needle and a polypropylene plunger (supplied separately from the syringe) for administration of the product.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Instituto Grifols, S.A.
Can Guasch, 2 - Parets del Vallès
08150 Barcelona - SPAIN