VENBIG 50 IU/ml Powder

Contents of the leaflet

1. Leaflet accompanying the packaging: information for the user
2. VENBIG 50 IU/ml powder and solvent for solution for infusion
3. Human immunoglobulin against viral hepatitis B
   1. You should carefully read the contents of the leaflet before using the medicine because it contains important information for the patient.
4. What is VENBIG and what is it used for
5. Important information before using VENBIG
   1. When not to use VENBIG
   2. Warnings and precautions
   3. In certain cases, immunoglobulins may increase the risk of heart attack, stroke, pulmonary embolism, or worsen deep vein thrombosis, as they increase blood viscosity.
   4. The patient may be allergic (hypersensitive) to immunoglobulin (antibodies) without knowing it.
   5. Children and adolescents
   6. VENBIG and other medicines
   7. Pregnancy, breastfeeding, and fertility
   8. Driving and using machines
   9. VENBIG contains sodium and sugar
6. How to use VENBIG
   1. Using a higher dose of VENBIG than recommended
7. Possible side effects
   1. If you experience any of the following side effects, contact your doctor or the nearest hospital immediately:
   2. Additional side effects in children and adolescents
   3. Reporting side effects
8. How to store VENBIG
9. Contents of the pack and other information
   1. What VENBIG contains
   2. What VENBIG looks like and what the pack contains
   3. Marketing authorization holder
   4. Manufacturer
   5. Information intended for healthcare professionals only:
   6. Instructions for use:
   7. Special precautions
   8. Dosing recommendations

Leaflet accompanying the packaging: information for the user

VENBIG 50 IU/ml powder and solvent for solution for infusion

Human immunoglobulin against viral hepatitis B

For intravenous use

You should carefully read the contents of the leaflet before using the medicine because it contains important information for the patient.

• You should keep this leaflet, so you can read it again if you need to.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• If you experience any side effects, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of contents of the leaflet:

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

1. What is VENBIG and what is it used for

VENBIG belongs to a pharmacotherapeutic group called: immunoglobulins.
VENBIG is a solution of human immunoglobulins (proteins that have antibody properties)
against viral hepatitis B for intravenous administration and is used in the following cases:
Prevention of re-infection with hepatitis B virus after liver transplantation due to liver failure caused by hepatitis B virus, in combination with antiviral therapy.
Immediate administration of antibodies against hepatitis B virus to prevent hepatitis B virus infection in the following cases:

• in case of accidental exposure of non-immune individuals (i.e., unvaccinated individuals against hepatitis B virus, including those whose vaccination has not been completed or whose status is unknown);
• in patients undergoing hemodialysis (these are patients with severe kidney failure who require blood purification using an artificial kidney), until vaccination takes effect;
• in newborns born to a mother carrying the hepatitis B virus;
• in individuals who do not respond to vaccination (i.e., individuals for whom vaccination is not effective) and those who require constant prophylaxis due to the risk of hepatitis B virus infection.

2. Important information before using VENBIG

When not to use VENBIG

• If the patient is allergic to human immunoglobulins or any of the other components of this medicine (listed in section 6).
• In patients with antibodies against immunoglobulin IgA in the blood, administration of a product containing IgA may cause severe allergic reactions.

Warnings and precautions

Before starting treatment with VENBIG, discuss it with your doctor, pharmacist, or nurse.
The use of intravenous normal human immunoglobulin (IVIg) has been associated with the occurrence of
vascular occlusion (thrombosis). It is recommended to exercise particular caution when administering the medicine to individuals with risk factors for thrombosis.
Regularly check the level of anti-HBs antibodies.
Some side effects may occur more frequently:

• in case of too rapid infusion;
• in patients with symptoms of untreated infection (e.g., fever) or chronic inflammatory conditions;
• in patients who receive human normal immunoglobulin for the first time;
• in rare cases, when the previously administered human normal immunoglobulin product is changed to another or when a long time has passed since the last infusion.

In certain cases, immunoglobulins may increase the risk of heart attack, stroke, pulmonary embolism, or worsen deep vein thrombosis, as they increase blood viscosity.

For this reason, the doctor will exercise particular caution in the following cases:

• in obese patients,
• in elderly patients,
• in patients with diabetes,
• in patients with high blood pressure (hypertension),
• in patients with reduced blood volume (hypovolemia),
• in patients with vascular diseases,
• in patients with a risk of blood clotting disorders (acquired or congenital coagulation disorders),
• in patients with a history of thrombotic events
• in patients with conditions characterized by increased blood viscosity,
• in patients who are bedridden for a long time,
• in patients with kidney diseases currently or in the past, or taking medications that may damage the kidneys (nephrotoxic drugs), as cases of acute kidney failure have been reported. In case of kidney function impairment, the doctor will consider discontinuing immunoglobulin administration.

The patient may be allergic (hypersensitive) to immunoglobulin (antibodies) without knowing it.

Hypersensitivity may occur even in a patient who has previously received human normal immunoglobulin and tolerated it well. It may occur especially in cases of IgA deficiency (IgA deficiency with anti-IgA antibodies). In these rare cases, allergic reactions (hypersensitivity) such as a sudden drop in blood pressure or anaphylactic reaction may occur.
The recommendations for infusion rate given in section 3 "How to use VENBIG" must be strictly followed by the doctor due to the possibility of certain side effects related to the infusion rate. The patient must be monitored and closely observed during infusion to check for unwanted symptoms.
In case of an adverse reaction, the doctor will decide whether to reduce the infusion rate or discontinue the administration of the medicine. Additionally, the doctor will decide on the treatment method depending on the severity and intensity of the adverse reaction.
VENBIG contains a small amount of IgA. Individuals with IgA deficiency have a potential tendency to develop IgA antibodies, and after administration of blood components containing IgA, they may experience anaphylactic reactions. Therefore, the doctor should analyze the benefits of treatment with VENBIG in relation to the potential risk of hypersensitivity reactions.
Rarely, human immunoglobulin against hepatitis B virus may lead to a drop in blood pressure with anaphylactic shock, even in patients who have previously tolerated immunoglobulin treatment well.
In case of suspected allergic or anaphylactic reaction, infusion should be stopped immediately. In case of shock, treatment for shock should be administered in accordance with current medical standards.
You should tell your doctor if any of the above conditions apply to you, as the doctor will take appropriate precautions when prescribing and administering VENBIG to you.
Human immunoglobulins for intravenous administration may contain antibodies against blood groups, which can cause red blood cell lysis (hemolysis). As a result, during treatment with human immunoglobulins, a form of anemia (hemolytic anemia) may develop due to abnormal red blood cell destruction. Patients receiving intravenous immunoglobulin products (IVIg) should be monitored for subjective and objective symptoms of hemolysis.
Effect on blood test results
VENBIG may affect some blood test results due to the transient increase in passively transferred antibodies in the blood after immunoglobulin injection; the increase in these antibodies may cause false-positive serological test results. The passive transfer of antibodies against erythrocyte antigens, such as A, B, D (which determine blood group), may affect the results of some serological tests for red blood cell antibodies, such as the antiglobulin test (Coombs test).
Prevention of viral infections
When medicines are prepared from human blood or plasma, certain preventive measures are taken to prevent the transmission of infections to patients. These measures include:

• careful selection of blood and plasma donors to eliminate the risk of transmission of infections;
• testing each blood donation and plasma pool for the presence of infectious agents and/or viruses;
• including virus inactivation or removal processes in the manufacturing process.

However, despite these measures, during the administration of medicines derived from human blood or plasma, it is not possible to completely exclude the potential possibility of transmitting infectious agents. This also applies to unknown or newly emerging viruses or other types of infections.
The methods used are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as non-enveloped viruses, such as hepatitis A virus (HAV).
Measures taken against non-enveloped viruses, such as parvovirus B19, may have limited significance.
It should not be associated with the possibility of infection with hepatitis A virus or parvovirus B19, as the antibodies against these infections contained in the product have a protective character.
It is very important to follow the recommendation to record the name and batch number of the product each time a dose of VENBIG is administered, so that in the future, it can be determined which batch of the product the patient received.

Children and adolescents

There are no special precautions or monitoring requirements.

VENBIG and other medicines

Tell your doctor or pharmacist about all medicines you are taking or have recently taken, as well as any medicines you plan to take.
Human immunoglobulin against hepatitis B virus for intravenous administration must not be mixed with other medicines.
Vaccines containing live attenuated viruses
VENBIG may affect the immune response after administration of vaccines containing live attenuated viruses, such as rubella, mumps, measles, and chickenpox. Administration of immunoglobulins may weaken the effectiveness of these vaccines for up to 3 months. After administration of VENBIG, a minimum of 3 months should be allowed before administering vaccines containing live attenuated viruses.
Human immunoglobulin against hepatitis B virus should be administered 3 to 4 weeks after vaccination with a live attenuated virus vaccine. If human immunoglobulin against hepatitis B virus needs to be administered within 3 to 4 weeks after vaccination, a repeat vaccination should be performed 3 months after administration of human immunoglobulin against hepatitis B virus.
Loop diuretics (a group of medicines that increase urine flow)
Concomitant use of VENBIG with loop diuretics should be avoided.

Pregnancy, breastfeeding, and fertility

• If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor or pharmacist for advice before using this medicine. The doctor will decide whether VENBIG can be used in pregnant women.
• No clinical studies have been conducted with VENBIG in pregnant women. It has been shown that intravenous immunoglobulin products cross the placenta, with increased intensity during the third trimester. However, long-term clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, the fetus, or the newborn are expected.
• If you are breastfeeding and receiving VENBIG, the antibodies from this medicine may pass into human milk. This may contribute to the protection of the newborn against certain infections.
• Clinical experience with immunoglobulins suggests that no harmful effects on fertility are expected.

Driving and using machines

VENBIG has no or negligible influence on the ability to drive and use machines. Patients who experience side effects during treatment should wait for them to resolve before driving or operating machines.

VENBIG contains sodium and sugar

This medicine contains up to 39 mg of sodium per 10 ml vial and up to 175.5 mg of sodium per 45 ml vial, which corresponds to 1.9% and 8.7% of the maximum recommended daily intake of sodium in the diet for adults.
This medicine contains up to 92 mg of sucrose per ml (91.9 mg/ml). This should be taken into account in patients with a risk of acute kidney failure.

3. How to use VENBIG

VENBIG should only be administered by qualified medical personnel in a hospital setting.
Dosage and treatment regimen depend on the indications. The doctor will determine the appropriate dosage and treatment method.
VENBIG is administered intravenously in an infusion, initially slowly. If the medicine is well tolerated, the doctor may gradually increase the infusion rate.
For more information, see the "Information intended for healthcare professionals only" section.

Using a higher dose of VENBIG than recommended

The consequences of overdose are not known.
Overdose may lead to circulatory overload and excessive blood viscosity, especially in patients at risk, including elderly patients or those with heart or kidney failure.
If you have any further questions about using this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

If you experience any of the following side effects, contact your doctor or the nearest hospital immediately:

:

• Allergic reaction (hypersensitivity). In some cases, a severe allergic reaction (anaphylactic shock) may develop: e.g., itching, skin reactions, swelling of the lips, face, and tongue, difficulty swallowing, breathing difficulties, fainting.
• Acute kidney failure (e.g., decreased or absent urine excretion, fluid retention, shortness of breath).

The following side effects may occur after intravenous administration of normal human immunoglobulins:

• rarely, chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate lower back pain;
• isolated cases of temporary reduction in red blood cell count (reversible hemolytic reactions/hemolysis); particularly in patients with blood groups A, B, and AB, and (rarely) hemolytic anemia requiring transfusion;
• rarely, a sudden drop in blood pressure and, in isolated cases, hypersensitivity reactions (anaphylactic shock), even in patients who did not experience hypersensitivity after previous administrations;
• observed rare cases of transient skin reactions;
• very rarely, thromboembolic complications (formation of blood clots) have been reported, which can cause heart attack, stroke, pulmonary embolism, and deep vein thrombosis;
• cases of transient non-infectious meningitis (reversible aseptic meningitis);
• cases of increased serum creatinine levels and/or acute kidney failure;
• cases of acute transfusion-related lung injury (TRALI).

After the marketing authorization of VENBIG, the following side effects have been reported (frequency cannot be estimated from the available data):

• Headache
• Increased heart rate (tachycardia)
• Low blood pressure (hypotension)
• Nausea
• Vomiting
• Skin reactions: redness (flush), itching, pruritus
• Joint pain
• Fever
• Malaise
• Chills

For additional information on the prevention of viral infections, see "2. Important information before using VENBIG".

Additional side effects in children and adolescents

There are no special data available for children and adolescents.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, tell your doctor or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocides of the Office for Registration of Medicinal Products, Medical Devices, and Biocides:
Al. Jerozolimskie 181C, 02-222 Warsaw, tel: 22 4921301, fax: 22 4921309, e-mail:
[email protected]
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store VENBIG

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date (EXP) stated on the label and carton. The expiry date refers to the last day of the month.
Store in a refrigerator (2°C - 8°C).
Keep the product in the outer carton in order to protect it from light.
Do not freeze.
VENBIG should be used immediately after reconstitution in the solvent.
Do not use VENBIG if the solution is cloudy, contains sediment, or has changed color (see also "What VENBIG looks like and what the pack contains" in section 6)
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What VENBIG contains

The active substance is human immunoglobulin against hepatitis B virus.

The distribution of IgG subclasses is as follows:
IgG1 26.0 – 40.0 mg/ml
IgG2 13.0 – 25.0 mg/ml
IgG3 1.20 – 2.50 mg/ml
IgG4 0.15 – 0.50 mg/ml
Maximum IgA content: 0.05 mg/ml
The medicine is produced from plasma of blood donors.
Other ingredients are sucrose, sodium chloride, and water for injections.
The vial with powder contains human immunoglobulin against hepatitis B virus, sucrose, and sodium chloride.
The vial with solvent contains sodium chloride and water for injections.

What VENBIG looks like and what the pack contains

The VENBIG pack contains a vial with powder and a vial with solvent, from which a solution for infusion is prepared.
The powder is white or pale yellow, or in the form of a fine solid mass.
After reconstitution, the product is a clear or slightly opalescent, colorless or pale yellow liquid.
The solution after reconstitution should be visually inspected for the presence of particles and color. Do not use solutions that are cloudy or contain sediment.
VENBIG 50 IU/ml powder and solvent for solution for infusion
500 IU vial with powder + 10 ml vial with solvent + infusion set (1 syringe with needle + 1 needle for administration)
2500 IU vial with powder + 45 ml vial with solvent + infusion set.

Marketing authorization holder

Kedrion S.p.A. - Loc. Ai Conti, 55051 Castelvecchio Pascoli, Barga (Lucca) Italy.

Manufacturer

Kedrion S.p.A. - S.S. 7 bis Km 19,5, S. Antimo (Naples), Italy.
To obtain more detailed information, contact the representative of the marketing authorization holder:
MB&S Medical Business and Science
ul. Chełmska 30/34, 00-725 Warsaw
tel. 22 851 52 09
Date of last revision of the leaflet:11/2019

Information intended for healthcare professionals only:

Instructions for use:

The medicine should be brought to room temperature or body temperature before use.
Complete reconstitution should be achieved within 30 minutes.
VENBIG should be administered intravenously in an infusion, initially at a rate of 0.46 – 0.92 ml/kg/hour (e.g., for a patient weighing 65 kg: 10 – 20 drops/minute) for 20 – 30 minutes. In case of an adverse reaction, the infusion rate should be reduced or administration stopped. If the medicine is well tolerated, the infusion rate can be gradually increased to a maximum of 1.85 ml/kg/hour (e.g., for a patient weighing 65 kg: 40 drops/minute) until the end of the infusion.
Reconstitution of the solution, 500 IU vial:

• 1. Draw the solvent into the syringe;
• 2. Inject the solvent into the vial with the lyophilized substance using the same syringe;
• 3. Gently shake the vial until the powder is completely dissolved; do not shake vigorously to avoid foaming;
• 4. Draw the resulting solution into the syringe;
• 5. Change the needle and administer to the patient in an infusion.

Reconstitution of the solution, 2500 IU vial:

• 1. Remove the protective caps from the vials with powder and solvent;
• 2. Wipe the surfaces of the vial stoppers with spirit;
• 3. Insert the smaller needle of the double needle into the vial with solvent;
• 4. Remove the needle shield from the other end of the double needle; be careful not to touch the other needle accidentally;
• 5. Invert the vial with solvent with the double needle and insert the other needle into the vial with powder; when piercing the stopper of the vial with powder, the tip of the needle in the vial with solvent should be immersed in the liquid and not in contact with air;
• 6. Gently shake the vial at room temperature until the powder is completely dissolved; do not shake vigorously to avoid foaming;
• 7. Remove the vial with solvent from the double needle;
• 8. Administer in an intravenous infusion using the infusion set. Before administration, the reconstituted products should be visually inspected for the presence of particles and color. The reconstituted solution is clear or slightly opalescent, colorless or pale yellow. Do not use cloudy or sediment-containing solutions.

VENBIG should be used immediately after reconstitution in the solvent.
Any unused product or waste material should be disposed of in accordance with local regulations.

Special precautions

Some severe adverse reactions to the product may be related to the infusion rate.
Potential complications can often be avoided by ensuring that:

• patients are not allergic to human normal immunoglobulin through initial slow administration of the product (infusion rate 0.46 - 0.92 ml/kg/hour);
• patients are closely monitored during infusion for adverse reactions. Especially patients receiving human normal immunoglobulin for the first time, patients who have previously received another IVIg product, or in case of a long interval since the last infusion, should be monitored during the first infusion and for the first hour after the first infusion to detect potential adverse reactions. Other patients should be observed for at least 20 minutes after infusion.

In all patients, intravenous administration of IVIg requires:

• adequate hydration before starting IVIg infusion
• monitoring of urine output
• monitoring of serum creatinine levels
• avoiding concomitant use of loop diuretics.

In case of an adverse reaction, the infusion rate should be reduced or immunoglobulin administration stopped. Treatment depends on the type and severity of the adverse reaction.
In case of shock, treatment for shock should be administered in accordance with current medical standards.
Infusion reaction
Some adverse reactions (e.g., headache, flushing, chills, muscle pain, wheezing, tachycardia, lower back pain, nausea, and hypotension) may depend on the infusion rate. The recommended infusion rate should be strictly followed. Patients must be closely monitored and observed during infusion due to the risk of adverse reactions.
Some adverse reactions may occur more frequently:

• in case of too rapid infusion rate;
• in patients with hypogammaglobulinemia with or without IgA deficiency.

Hypersensitivity
True allergic reactions are rare.
VENBIG contains a small amount of IgA. Individuals with IgA deficiency have a potential tendency to develop IgA antibodies, and after administration of blood components containing IgA, they may experience anaphylactic reactions. Therefore, the doctor should analyze the benefits of treatment with VENBIG in relation to the potential risk of hypersensitivity reactions.
Rarely, human immunoglobulin against hepatitis B virus may lead to a drop in blood pressure with anaphylactic shock, even in patients who have previously tolerated immunoglobulin treatment well.
You should inform patients about the first symptoms of hypersensitivity reactions, such as hives, generalized hives, feeling of chest tightness, wheezing, hypotension, and anaphylaxis. The treatment depends on the type and severity of the adverse reaction.
Suspicion of an allergic or anaphylactic reaction requires immediate cessation of infusion. In case of shock, treatment for shock should be administered in accordance with current medical standards.
Effect on serological test results
After immunoglobulin injection, a transient increase in passively transferred antibodies in the patient's blood may occur, causing false-positive serological test results. The passive transfer of antibodies against erythrocyte antigens, such as A, B, D, may affect the results of some serological tests for red blood cell antibodies, such as the antiglobulin test (Coombs test).
Infectious agents
Standard measures to prevent infections associated with the use of medicinal products derived from human blood or plasma include donor selection, screening tests for individual donations and plasma pools for the presence of specific infection markers, and the introduction of effective virus inactivation/removal steps in the manufacturing process. However, during the administration of medicinal products derived from human blood or plasma, it is not possible to completely exclude the potential possibility of transmitting infectious agents. This also applies to unknown or newly emerging viruses or other types of infections.
The methods used are considered effective against enveloped viruses, such as human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), as well as non-enveloped viruses, such as hepatitis A virus (HAV).
Measures taken against non-enveloped viruses, such as parvovirus B19, may have limited significance.
It is recommended that each time a patient is administered VENBIG, the product name and batch number should be recorded, so that in the future, it can be determined which batch of the product the patient received.
Important information about some ingredients of VENBIG
This medicinal product contains up to 39 mg of sodium per 10 ml vial and up to 175.5 mg of sodium per 45 ml vial, which corresponds to 1.9% and 8.7% of the maximum recommended daily intake of sodium in the diet for adults.
This medicinal product contains up to 92 mg of sucrose per ml (91.9 mg/ml). This should be taken into account in patients with a risk of acute kidney failure.
The following adverse reactions may be associated with the use of intravenous normal human immunoglobulin (IVIg):
Thromboembolic events
There is clinical evidence of a link between intravenous immunoglobulin administration and thromboembolic events, such as heart attack, stroke, pulmonary embolism, and deep vein thrombosis, which are thought to be related to the relative increase in blood viscosity after intensive immunoglobulin administration in patients at risk. Caution should be exercised when prescribing and administering IVIg to patients who are obese or have a history of thrombotic events (such as advanced age, hypertension, diabetes, vascular disease, or thrombotic events in their history, acquired or congenital coagulation disorders, prolonged immobilization, patients with severe hypovolemia, patients with conditions characterized by increased blood viscosity).
In patients at risk of thromboembolic events, intravenous immunoglobulins should be administered at the minimum infusion rate and in the smallest possible dose.
Acute kidney failure
Cases of acute kidney failure have been reported in patients treated with intravenous immunoglobulins. In most cases, risk factors were identified, such as pre-existing kidney failure, diabetes, reduced blood volume, overweight, concomitant use of nephrotoxic products, or age over 65. Renal function should be assessed before IVIg administration and again at appropriate intervals, especially in patients with potential increased risk of acute kidney failure. In patients at risk of acute kidney failure, IVIg should be administered at the minimum infusion rate and in the smallest possible dose. In case of impaired kidney function, discontinuation of intravenous immunoglobulin administration should be considered. Although reports of renal impairment and acute kidney failure were associated with the use of several approved IVIg products containing different excipients, such as sucrose, glucose, and maltose, products containing sucrose as a stabilizer had a disproportionately high share of the total number of cases. In patients at risk, consideration can be given to using IVIg products that do not contain these excipients.
VENBIG contains sucrose (see section 2, paragraph "VENBIG contains sodium and sugar").
Aseptic meningitis syndrome
During treatment with IVIg, cases of aseptic meningitis syndrome (AMS) have been reported. The syndrome usually starts within a few hours to 2 days after IVIg administration. In cerebrospinal fluid examinations, pleocytosis is often found, with several thousand cells per mm, mainly granulocytes, and elevated protein levels. Patients with these objective and subjective symptoms should undergo a thorough neurological examination, including cerebrospinal fluid examination, to rule out other causes of meningitis.
Discontinuation of IVIg treatment resulted in remission of AMS within a few days without sequelae.
Hemolytic anemia
Intravenous immunoglobulin products may contain antibodies against blood groups, which can act as hemolysins and activate in vivocoating of red blood cells with immunoglobulin, causing a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia may be a consequence of IVIg treatment due to increased red blood cell destruction. Patients receiving IVIg should be monitored for subjective and objective symptoms of hemolysis.
Neutropenia/leukopenia
After IVIg treatment, transient decreases in neutrophil count and/or episodes of neutropenia have been reported, sometimes severe. This usually occurs within a few hours or days after IVIg administration and resolves spontaneously within 7 to 14 days.
Acute transfusion-related lung injury (TRALI)
Cases of acute transfusion-related lung injury (TRALI) have been reported in patients receiving IVIg products. TRALI is characterized by severe hypoxia, respiratory failure, respiratory distress, cyanosis, fever, and hypotension. TRALI symptoms usually occur within 6 hours after IVIg administration, often within 1-2 hours. Therefore, patients should be monitored; in case of respiratory adverse reactions, IVIg infusion should be stopped immediately. The occurrence of TRALI can be life-threatening and requires immediate treatment in an intensive care unit.
Children and adolescents
There are no special precautions or monitoring requirements.

Dosing recommendations

Dosage
The dosage and treatment regimen depend on the indications. The following dosing regimens are provided as guidelines.
Prevention of re-infection with hepatitis B virus after liver transplantation due to liver failure caused by hepatitis B virus:

• 10,000 IU on the day of transplantation, during surgery; then 2,000-10,000 IU/day for 7 days, and if necessary, to maintain antibody levels above 100-150 IU/l in patients with negative HBV-DNA and above 500 IU/l in patients with positive HBV-DNA.

Children and adolescents
Dosage should be determined based on body surface area, at a ratio of 10,000 IU/1.73 m.
Prevention of hepatitis B virus infection

• Prophylaxis against hepatitis B virus infection in case of accidental exposure of non-immune individuals: at least 500 IU, depending on the intensity of exposure, as soon as possible after exposure; best within 24-72 hours.
• Immunoprophylaxis against hepatitis B virus infection in patients undergoing hemodialysis: 8-12 IU/kg, up to 500 IU, every 2 months, until vaccination takes effect.
• Prophylaxis against hepatitis B virus infection in newborns born to mothers carrying the hepatitis B virus, for administration at birth or as soon as possible after birth: 30-100 IU/kg. In clinical practice, intramuscular administration is the preferred route of administration when repeated vaccinations are necessary to achieve antibody formation. Administration of human immunoglobulin against hepatitis B virus can be repeated until seroconversion is achieved.

In all these cases, vaccination against hepatitis B virus is particularly recommended. The first dose of vaccine can be administered on the same day as human immunoglobulin against hepatitis B virus, but in different parts of the body.
For individuals who do not respond to vaccination (i.e., hepatitis B virus antibodies are not detectable) and those who require constant prophylaxis due to the risk of hepatitis B virus infection, administration of 500 IU every 2 months for adults and 8 IU/kg for children can be considered; the minimum protective antibody level is considered to be 10 IU/ml.
Other official guidelines for dosing and dosing regimens of human immunoglobulin against hepatitis B virus for intravenous administration should also be taken into account.