NEOHEPATECT 2 ML/100 U.I. Infusion solution

Зміст інструкції

1. neoHepatect 50 UI/ml solution for infusion
   1. What is neoHepatect and what is it used for
   2. What you need to know before using neoHepatect
   3. How to use neoHepatect
   4. Possible side effects
   5. How to store neoHepatect
   6. Content of the pack and other information

neoHepatect 50 UI/ml solution for infusion

Human anti-hepatitis B immunoglobulins for intravenous administration

Information for healthcare professionals is reported at the end of this leaflet, in a separate paragraph.
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 pass it on to others, even if they have the same symptoms as you, as it may be harmful.
• If any side effects occur, including any not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What is neoHepatect and what is it used for

neoHepatect contains human anti-hepatitis B immunoglobulins as its active ingredient, which can
protect against hepatitis B. Hepatitis B is an inflammation of the liver caused by the hepatitis

• B virus. neoHepatect is a solution for infusion (into a vein) and is available in vials containing 2 ml (100 international units [IU]), 10 ml (500 IU), 40 ml (2000 IU) and 100 ml (5000 IU).

neoHepatect is used to provide immediate and long-term immunity (protection) for:

• preventing hepatitis B infection in patients who have not been vaccinated or are not yet fully vaccinated against hepatitis B and who are at risk of hepatitis B infection.
• preventing infection of a transplanted liver in patients who test positive for hepatitis B.
• newborns whose mothers are infected with the hepatitis B virus
• protecting patients for whom vaccination against hepatitis B has not provided adequate protection.

2. What you need to know before using neoHepatect

Do not use neoHepatect

• if you are allergic to human immunoglobulins or to any of the other ingredients of this medicine (listed in section 6).
• if you have a deficiency of immunoglobulin A (IgA), especially if you have antibodies against IgA in your blood, as this may cause anaphylaxis.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before using neoHepatect if

• you have not received this medicine previously or if there has been a long interval (e.g. many weeks) since the last time you received it (you will need to be closely monitored during the infusion and for one hour after the infusion is stopped)
• you have recently received neoHepatect (you will need to be monitored during the infusion and for at least 20 minutes after the infusion)
• you have an untreated infection or underlying chronic inflammation
• you have had a reaction to other antibodies (in rare cases, you may be at risk of allergic reactions)
• you have, or have had, kidney disease
• you are taking medicines that can damage the kidneys (if kidney function worsens, it may be necessary to stop treatment with neoHepatect) Your doctor will be particularly careful if you are overweight, elderly, diabetic or if you suffer from high blood pressure, low blood volume (hypovolemia), if the blood is thicker than normal (elevated blood viscosity), if you have been bedridden or immobile for a certain period (immobilization) or if you have blood vessel problems (vascular diseases) or other risk factors for thrombotic events (blood clots).

Caution - reactions
You will be closely monitored during the infusion with neoHepatect, to ensure that you do not have
a reaction (e.g. anaphylaxis). The doctor will ensure that the infusion rate of neoHepatect is
appropriate for you.
If you experience any of the following signs of a reaction, such as headache, flushing, chills,
muscle pain, wheezing, rapid heartbeat, lower back pain, nausea, low blood
pressure during the infusion of neoHepatect, immediately inform your doctor. The infusion rate may be reduced or the infusion may be stopped completely.

Information on the transmission of infectious agents
neoHepatect is made from human plasma (the liquid part of the blood).
Certain measures are taken for medicines derived from blood or human plasma to
prevent infections from being transmitted to patients. These include:

• careful selection of plasma and blood donors, to exclude individuals who might be carrying infections,
• testing each donation and total plasma for signs of viruses/infection,
• adding steps capable of inactivating or removing viruses during the processing of blood or plasma.

Despite these measures, when medicines derived from blood or human plasma are administered,
the risk of transmission of infections cannot be completely eliminated. This also applies
to any unknown or new viruses or other types of infection.
The measures taken are considered effective against enveloped viruses, such as the human
immunodeficiency virus (HIV), hepatitis B virus and hepatitis C virus.
The measures taken may be of limited effectiveness against non-enveloped viruses, such as the
hepatitis A virus and parvovirus B19.
Immunoglobulins have not been associated with hepatitis A or parvovirus B19 infection,
likely because the antibodies directed against these infections and contained in the product are
protective.
It is strongly recommended that you note the name and batch number of the medicine
whenever the patient receives a dose of neoHepatect, in order to keep a record
of the batches used.

Other medicines and neoHepatect
Tell your doctor or pharmacist if you are taking, have recently taken or might take
any other medicines.
neoHepatect may reduce the effectiveness of some vaccines, such as those against:

• measles
• rubella
• mumps
• chickenpox You may need to wait up to 3 months before being able to get vaccinated and up to a year before the measles vaccine.

Avoid concomitant use of loop diuretics with neoHepatect.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect you are pregnant, are planning to become pregnant, or are breastfeeding
with breast milk, ask your doctor or pharmacist for advice before taking this medicine.
Your doctor will decide whether neoHepatect can be used during pregnancy and breastfeeding.

Driving and operating machinery
neoHepatect may slightly impair the ability to drive vehicles or operate machinery. If
you experience any adverse reactions during treatment, you should wait for these to resolve,
before driving vehicles or operating machinery

3. How to use neoHepatect

neoHepatect is intended for intravenous administration (infusion into a vein). The product is
administered by a doctor or a nurse. The recommended dose will depend on the clinical
conditions and body weight. The doctor will establish the correct amount to administer.
Initially, the infusion rate of neoHepatect will be low, but the doctor may then increase it
gradually.
If you have any further questions about the use of this product, please consult your doctor or nurses.

4. Possible side effects

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

The following side effects have been reported spontaneously with neoHepatect:
Not known: the frequency cannot be estimated based on the available data

• severe allergic reactions (anaphylactic shock)
• hypersensitivity reactions
• headache
• dizziness
• increased heart rate (tachycardia)
• low blood pressure (hypotension)
• nausea
• skin (cutaneous) reactions such as rash, itching
• fever
• malaise

Normal human immunoglobulin preparations can cause the following side effects
(in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure and moderate back pain
• reduction in the number of red blood cells due to breakdown of these cells in blood vessels (hemolytic reactions (reversible)) and (rarely) hemolytic anemia requiring transfusion
• (rarely) sudden drop in blood pressure and, in isolated cases, anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus - frequency not known)
• (very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, blood clots in the blood vessels of the lung (pulmonary embolism), blood clots in a vein (deep vein thrombosis)
• cases of temporary acute inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of blood test results indicating impaired kidney function and/or acute renal failure
• cases of acute transfusion-related lung injury (TRALI). This will lead to an accumulation of fluid, not related to the heart, in the air spaces of the lungs (non-cardiogenic pulmonary edema). You will experience severe difficulty breathing (respiratory distress), rapid breathing (tachypnea), abnormally low levels of oxygen in the blood (hypoxia), and increased body temperature (fever).

If a side effect occurs, the infusion should be slowed down or stopped completely.

Reporting of side effects
If you get any side effects, even those not listed in this leaflet, tell your doctor, pharmacist or nurse. You can also report side effects directly
through the national reporting system at 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 neoHepatect

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 packaging and on the
vial label.
Keep the vial in the outer packaging to protect the medicine from light. Store in
a refrigerator (2 °C – 8 °C). Do not freeze.
The solution must be clear or slightly opalescent and from colourless to pale yellow. Do not
use solutions that are cloudy or contain deposits.
The solution should be administered immediately after opening the container. The product must
be brought to room or body temperature before use.
Do not dispose of any medicine in wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Content of the pack and other information

What neoHepatect contains:

• The active ingredient of neoHepatect consists of human anti-hepatitis B immunoglobulins for intravenous administration. neoHepatect contains 50 mg/ml of human plasma proteins, consisting of at least 96% immunoglobulin G (IgG). The content of anti-hepatitis B antibodies is at least 50 IU/ml. The maximum content of immunoglobulin A (IgA) is 2,000 micrograms/ml. The distribution of IgG subclasses is approximately 59% IgG1, 35% IgG2, 3% IgG3 and 3% IgG4.
• The excipients are glycine and water for injections.

Description of the appearance of neoHepatect and contents of the pack
neoHepatect is a solution for infusion. The solution is transparent or weakly opalescent (a
milky coloration, similar to that of opal) and colorless or pale yellow.
Pack containing 1 vial of 2 ml, 10 ml, 40 ml or 100 ml of solution.

Marketing authorisation holder and manufacturer:
Biotest Pharma GmbH
Landsteinerstrasse 5
63303 Dreieich
Germany
Tel.: + 49 6103 801-0
Fax: + 49 6103 801-150
Email: [email protected]
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The following information is intended exclusively for doctors or healthcare professionals:
Route of administration
Intravenous use
neoHepatect should be administered by intravenous infusion at an initial rate of 0.1 ml/kg of body
weight/hour for 10 minutes. In case of adverse reaction, reduce the administration rate or
interrupt the infusion. If well tolerated, the administration rate may be gradually
increased to a maximum of 1 ml/kg/hour.
Clinical experience in neonates of mothers carrying hepatitis B virus has shown that the
intravenous administration of neoHepatect at an infusion rate of 2 ml in 5-15 minutes is well
tolerated.

Special precautions
Monitoring of anti-HBs antibody levels
Patients should be regularly monitored to supervise serum levels of anti-HBs antibodies.
The dosage should be adjusted to maintain therapeutic antibody levels and to avoid an
underdosage (see section Dosage).
Especially when administered at high doses, the administration of human immunoglobulins intravenously requires:

• adequate hydration before starting the immunoglobulin infusion
• monitoring of urinary excretion
• monitoring of serum creatinine levels
• exclusion of concomitant use of loop diuretics.

In case of adverse reaction, reduce the administration rate or interrupt the infusion. The
treatment required depends on the nature and severity of the adverse reaction.
Hypersensitivity
Hypersensitivity reactions are rare. Rarely, human anti-hepatitis B immunoglobulins may
induce a drop in blood pressure with anaphylactic reaction, even in patients who have
tolerated a previous treatment with immunoglobulins.
Suspicion of allergic or anaphylactic reactions requires immediate suspension of the injection.
In case of shock, standard medical treatment for shock must be initiated.

The following adverse reactions have been associated with the use of normal human immunoglobulins for

intravenous administration (IgIV):
Thromboembolism
There is clinical evidence of an association between the administration of IgIV and thromboembolic events, such as
myocardial infarction, cerebrovascular accidents (including stroke), pulmonary embolism and
deep vein thrombosis, which are presumed to be related to a relative increase in blood viscosity,
determined by the high influx of immunoglobulins in patients at risk. The prescription
and infusion of IgIV requires caution in obese patients and in patients with pre-existing risk factors for
thrombotic events (such as advanced age, hypertension, diabetes mellitus and a history of vascular disease or
thrombotic episodes, patients with acquired or hereditary thrombophilic disorders, patients with
prolonged periods of immobilization, patients with severe hypovolemia, patients with diseases that
increase blood viscosity).
In patients at risk of thromboembolic adverse reactions, IgIV products should be
administered at the lowest practicable infusion rate and dose.
Acute renal insufficiency
Cases of acute renal insufficiency have been reported in patients receiving IgIV therapy.
In most cases, risk factors such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, overweight, concomitant use of
nephrotoxic drugs or age over 65 years have been identified.
Check renal parameters before IgIV infusion, particularly in patients judged to be at
potentially increased risk of developing acute renal insufficiency, and again at appropriate intervals.
In patients at risk of acute renal insufficiency, IgIV products should be
administered at the lowest practicable infusion rate and dose. If renal impairment occurs, discontinuation of IgIV should be considered.
While reports of renal dysfunction and acute renal failure have been associated with the use
of many of the authorized IgIV products containing various excipients, such as sucrose, glucose and
maltose, those containing sucrose as a stabilizer represented a disproportionate share
of the total number.
In at-risk patients, the use of products containing human immunoglobulins without these excipients may be considered. neoHepatect does not contain sucrose, maltose or glucose.
Aseptic meningitis syndrome (AMS)
Aseptic meningitis syndrome has been reported in association with IgIV treatment.
The syndrome usually begins a few hours to 2 days after IgIV treatment. Studies on cerebrospinal fluid are frequently positive, with pleocytosis up to several thousand cells per mm ,
predominantly of the granulocytic series, and elevated protein levels up to several hundred mg/dl.
AMS may occur more frequently in association with treatment with high doses (2 g/kg) of
IgIV.
Patients presenting with such signs and symptoms should undergo a thorough neurological examination, including CSF studies, to exclude other causes of meningitis.
Discontinuation of IgIV treatment has led to remission of AMS within a few days without
sequelae.
Hemolytic anemia
IgIV products may contain anti-blood group antibodies that can act as
hemolysins and induce in vivo coating of red blood cells by immunoglobulins, causing
a positive direct antiglobulin reaction (Coombs' test) and, rarely, hemolysis. Anemia
hemolytic can develop following IgIV therapy, due to an increased sequestration of red blood cells (RBCs). Recipients of IgIV should be monitored for clinical signs and symptoms of
hemolysis.
Neutropenia/Leukopenia
Following treatment with IgIV, a transient decrease in the number of neutrophils and/or
episodes of neutropenia, sometimes severe, has been reported. This usually occurs within hours or days of
the administration of IgIV and resolves spontaneously within 7–14 days.
Transfusion-related acute lung injury (TRALI)
Cases of non-cardiogenic acute pulmonary edema have been described in patients receiving IgIV.
TRALI is characterized by severe hypoxemia, dyspnea, tachypnea, cyanosis, fever and arterial hypotension.
Symptoms of TRALI usually develop during or within 6 hours of the transfusion, often
within 1-2 hours. Therefore, recipients of IgIV should be monitored and the IgIV infusion should be
immediately interrupted in case of pulmonary adverse reactions. TRALI is a potentially life-threatening condition that requires immediate management in an intensive care unit.
Interference with serological tests
After the administration of immunoglobulin, the transient increase of various passively transferred antibodies in the patient's blood may result in false positive results in serological tests.

Dosage
Unless otherwise prescribed, the following recommendations apply:

Prevention of hepatitis B reinfection after liver transplantation for liver failure
caused by hepatitis B:
in adults:
Administer 10,000 IU of neoHepatect on the day of transplantation, during the surgical
procedure and subsequently 2,000 to 10,000 IU (40 ml to 200 ml) per day for seven days
and as needed to maintain antibody levels above 100-150 IU/l in HBV-negative patients
and above 500 IU/l in HBV DNA-positive patients
In children:
The dosage depends on the body surface area, based on 10,000 IU/1.73 m .

Hepatitis B immunoprophylaxis:

• Prevention of hepatitis B in case of accidental exposure to the virus in non-immune subjects: at least 500 IU (10 ml), depending on the intensity of exposure to the virus, as soon as possible after exposure and preferably within 24-72 hours.
• Hepatitis B immunoprophylaxis in hemodialyzed patients: 8-12 IU (0.16-0.24 ml)/kg up to a maximum of 500 IU (10 ml), every two months until seroconversion following vaccination.
• Prevention of hepatitis B in a newborn of a mother carrying the hepatitis B virus, at birth or as soon as possible after birth: 30-100 IU (0.6-2 ml)/kg. The administration of anti-hepatitis B immunoglobulin should be repeated until seroconversion following vaccination.

In all these situations, vaccination against hepatitis B virus is strongly recommended. The
first dose of vaccine can be injected on the same day as the administration of neoHepatect
but in a different area.
In subjects who do not show signs of an immune response (indeterminate anti-hepatitis B antibodies) following vaccination and for whom continuous prevention is necessary, the administration of 500 IU (10 ml) in adults and 8 IU (0.16 ml)/kg in children every
2 months may be considered; the minimum antibody titer for protection against the virus is 10 mIU/mL.