Hepatect Cp

Package Leaflet: Information for the User

Hepatect CP 50 IU/ml, Solution for Infusion

Human hepatitis B immunoglobulin for intravenous administration

Read the package leaflet carefully before using the medicine, as it contains important information for the patient.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

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

1. What is Hepatect CP and what is it used for

Hepatect CP contains human hepatitis B immunoglobulin as the active substance, which protects against hepatitis B infection caused by the hepatitis B virus. Hepatect CP is a solution for intravenous infusion and is available in vials containing 2 ml (100 IU), 10 ml (500 IU), 40 ml (2000 IU), and 100 ml (5000 IU) of the solution.

Hepatect CP is used to provide immediate and long-term protection (immunity):

• to prevent hepatitis B virus infection in patients who have not been vaccinated against hepatitis B or have not completed a full vaccination cycle and are at risk of infection.
• to prevent hepatitis B virus infection in liver transplant patients who have tested positive for hepatitis B virus.
• in newborns whose mothers are infected with hepatitis B virus.
• in patients who have not responded to hepatitis B vaccination.

2. Important information before using Hepatect CP

When not to use Hepatect CP

• if you are allergic to human immunoglobulin or 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 lead to anaphylaxis.

Warnings and precautions

Before starting treatment with Hepatect CP, discuss with your doctor, pharmacist, or nurse if:

• you have not received this medicine before or if there has been a long interval (e.g., several weeks) since the last administration of the medicine (you will need to be closely monitored during infusion and for one hour after the end of the infusion).
• you have recently received Hepatect CP (you will need to be monitored during infusion and for at least 20 minutes after the infusion).
• you have an untreated infection or a concomitant chronic inflammatory condition.
• you have had a reaction to other antibodies (in rare cases, there is a risk of allergic reactions).
• you have kidney disease.
• you have received medicines that may harm your kidneys (in case of worsening kidney function, it may be necessary to discontinue treatment with Hepatect CP). Your doctor will take special precautions in patients with overweight, elderly patients, patients with diabetes or high blood pressure, patients with low blood volume (hypovolemia), when blood viscosity is higher than normal (high blood viscosity), in immobilized patients, patients with vascular problems (vascular disease), or in cases of other risks of thrombotic events (blood clots).

Caution – reactions

You will be closely monitored during the administration of Hepatect CP to ensure that you do not experience any adverse reactions (e.g., anaphylaxis). Your doctor will check that the infusion rate is suitable for you.

If you experience any of the following reactions, such as headache, sudden heat, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, low blood pressure, during the infusion of Hepatect CP, inform your doctor immediately. The infusion rate can be reduced or stopped completely.

Information on the transmission of infectious agents

Hepatect CP is produced from human plasma (the liquid part of the blood).

For medicines produced from human blood or plasma, certain measures are taken to prevent the transmission of infections to patients. These include:

• careful selection of blood and plasma donors to ensure that donors who may be carrying infections are excluded.
• testing of individual blood donations and plasma pools for the presence of viruses/infections.
• incorporation of steps in the processing of blood or plasma that are designed to inactivate or remove viruses.

Despite these measures, the transmission of infection via medicines produced from human blood or plasma cannot be completely excluded. This also applies to unknown or emerging viruses or other types of infections.

The measures taken are considered effective against enveloped viruses such as human immunodeficiency virus (HIV), hepatitis B virus, and hepatitis C virus.

The measures taken may have limited effect against non-enveloped viruses such as hepatitis A virus and parvovirus B19.

No association has been found between immunoglobulins and hepatitis A or parvovirus B19 infections, possibly because the antibodies against these infections present in the product have a protective effect.

It is strongly recommended that every time you receive a dose of Hepatect CP, the name and batch number of the product should be recorded to keep a record of the batches used.

Hepatect CP and other medicines

Tell your doctor or pharmacist about all the medicines you are taking or have recently taken, as well as any medicines you plan to take.

Hepatect CP may reduce the effectiveness of some vaccines, such as:

• measles,
• rubella,
• mumps,
• chickenpox. It may be necessary to wait for up to three months before receiving certain vaccines and up to one year before receiving the measles vaccine.

Avoid concomitant use of loop diuretics with Hepatect CP.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, or think you may be pregnant, or plan to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Your doctor will decide whether you can use Hepatect CP during pregnancy and breastfeeding.

Driving and using machines

Hepatect CP has a minor influence on the ability to drive and use machines. If you experience side effects during treatment, wait for them to resolve before driving or using machines.

3. How to use Hepatect CP

Hepatect CP is intended for intravenous administration (intravenous infusion). It is administered to you by a doctor or nurse. The recommended dose depends on your health status and body weight. Your doctor will decide what dose to administer.

Initially, Hepatect CP is administered slowly. Your doctor may gradually increase the infusion rate.

Ask your doctor or nurse for advice or additional information if needed.

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 for Hepatect CP:

Frequency not known: frequency cannot be estimated from the available data

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

Human normal immunoglobulin products may 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
• decrease in red blood cell count due to the breakdown of these cells in the blood vessels ((reversible) hemolytic reactions) and (rarely) hemolytic anemia requiring transfusion
• (rarely) sudden drop in blood pressure and, in rare cases, anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus - frequency not known)
• (very rarely) thromboembolic reactions, such as myocardial infarction, stroke, blood clots in the lungs (pulmonary embolism), and blood clots in the veins (deep vein thrombosis)
• cases of transient acute inflammation of the membranes covering the brain and spinal cord (aseptic meningitis)
• cases of abnormal blood test results indicating kidney problems and (or) sudden kidney failure

If you experience side effects, the infusion rate will be reduced or stopped.

Reporting side effects

If you experience any side effects, including any not listed in this leaflet, please inform your doctor, pharmacist, or nurse. Side effects can be reported directly to the Department of Adverse Reaction Monitoring of Medicinal Products, Medical Devices, and Biocidal Products, Al. Jerozolimskie 181 C, 02-222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, e-mail: ndl@urpl.gov.pl. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Hepatect CP

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the carton and vial label.

Store the vial in the outer carton to protect from light.

Store in a refrigerator (2-8°C). Do not freeze.

The solution should be clear or slightly opalescent and colorless or pale yellow. Do not use solutions that are cloudy or contain particles.

The solution should be administered immediately after opening the packaging. The product should be brought to room temperature or body temperature before use.

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 Hepatect CP contains

• The active substance of Hepatect CP is human hepatitis B immunoglobulin for intravenous administration. Hepatect CP contains 50 mg/ml of human plasma protein, of which at least 96% is immunoglobulin G (IgG). The content of antibodies against hepatitis B is 50 IU/ml. The maximum content of immunoglobulin A (IgA) is 2000 micrograms/ml. The approximate distribution of IgG subclasses is: 59% IgG1, 35% IgG2, 3% IgG3, and 3% IgG4.
• The other ingredients are glycine and water for injection.

What Hepatect CP looks like and contents of the pack:

Hepatect CP is a solution for infusion. The solution is clear to slightly opalescent (milky appearance), colorless to pale yellow.

Package sizes: 1 vial containing 2 ml, 10 ml, 40 ml, or 100 ml of the solution.

Marketing authorization holder and manufacturer:

Biotest Pharma GmbH, Landsteinerstrasse 5, 63303 Dreieich, Germany, Tel.: +49 6103 801-0, Fax: +49 6103 801-150, E-mail: mail@biotest.com, Date of last revision of the leaflet: 11/2019

Information intended for healthcare professionals only:

Method of administration

Intravenous administration

Hepatect CP should be administered intravenously at an initial rate of 0.1 ml/kg body weight/hour for 10 minutes. If a side effect occurs, the infusion rate should be reduced or stopped. If it is well tolerated, the infusion rate can be gradually increased to a maximum rate of 1 ml/kg body weight/hour.

Clinical experience with newborns whose mothers were hepatitis B virus carriers has shown that Hepatect CP, administered intravenously in a dose of 2 ml over 5 to 15 minutes, is well tolerated.

Special precautions

Monitoring of anti-HBs antibody levels

In patients, the level of anti-HBs antibodies in serum should be regularly monitored. Dosing should be adjusted to maintain therapeutic levels of antibodies and avoid underdosing (see section Dosing).

Especially with high doses, intravenous administration of human immunoglobulin requires:

• adequate hydration before starting the infusion of human immunoglobulins,
• monitoring of urine output
• monitoring of serum creatinine levels
• avoiding concomitant use of loop diuretics.

If a side effect occurs, the infusion rate should be reduced or stopped. The required treatment depends on the type and severity of the side effect.

Hypersensitivity

Hypersensitivity reactions are rare. Human hepatitis B immunoglobulin may rarely cause a drop in blood pressure with anaphylactic reaction, even in patients who have previously tolerated immunoglobulin treatment well.

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

The following side effects have been associated with the use of human normal immunoglobulin for intravenous administration (IVIg):

Thromboembolic events

There is clinical evidence of a link between the administration of IVIg and thromboembolic events, such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis, which are considered to be related to the relative increase in blood viscosity associated with the high influx of immunoglobulin in patients at risk. Caution should be exercised when prescribing and administering IVIg to patients who are overweight and patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes, and vascular disease or a history of thrombotic events, patients with acquired or inherited tendencies to thrombosis, patients who are immobilized for a long time, patients with severe hypovolemia, and patients with conditions that increase blood viscosity). In patients with a history of thromboembolic events, IVIg products should be administered at the lowest possible dose and infusion rate.

Acute renal failure

Cases of acute renal failure have been reported in patients receiving IVIg treatment.

In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes, hypovolemia, overweight, concomitant use of nephrotoxic drugs, or age over 65.

Before IVIg infusion and subsequently at appropriate intervals, renal function should be evaluated, especially in patients at potential increased risk of acute renal failure. In patients with a history of renal failure, IVIg products should be administered at the lowest possible dose and infusion rate. If renal function deteriorates, consideration should be given to discontinuing intravenous immunoglobulin treatment.

Cases of dysfunction and acute renal failure have been observed after the administration of several licensed IVIg products containing different excipients, such as sucrose, glucose, and maltose, and products containing sucrose as a stabilizer accounted for the majority of such cases.

In patients at risk, consideration can be given to using human immunoglobulin products that do not contain these excipients. Hepatect CP does not contain sucrose, maltose, or glucose.

Aseptic meningitis syndrome (AMS)

AMS has been reported in association with IVIg treatment. The syndrome usually occurs within several hours to 2 days after IVIg treatment. In cerebrospinal fluid examinations, pleocytosis has often been found, with a cell count of up to several thousand cells/mm³, mainly granulocytes, and elevated protein levels of up to several hundred mg/dl.

AMS may occur more frequently in association with high-dose IVIg treatment (2 g/kg). Patients showing such objective and subjective symptoms should undergo a thorough neurological examination, including cerebrospinal fluid examinations, to rule out other causes of meningitis.

Discontinuation of IVIg treatment resulted in remission of AMS within several days without sequelae.

Hemolytic anemia

IVIg products may contain antibodies against blood groups, which can act as hemolysins and cause in vivocoating of red blood cells with immunoglobulins, resulting in a positive direct antiglobulin test (Coombs test), and rarely hemolysis. Hemolytic anemia may occur after IVIg treatment in association with increased red blood cell sequestration. Patients treated with IVIg should be monitored for clinical signs and symptoms of hemolysis.

Neutropenia/leukopenia

After IVIg treatment, transient decreases in neutrophil counts and (or) episodes of neutropenia have been reported, sometimes severe. This usually occurs within hours or days after IVIg administration and resolves spontaneously within 7-14 days.

Transfusion-related acute lung injury (TRALI)

TRALI has been reported in patients receiving IVIg. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever, and hypotension. TRALI symptoms usually occur during or within 6 hours after transfusion, often within 1-2 hours. For this reason, patients receiving IVIg should be monitored for pulmonary adverse reactions, and the infusion should be stopped immediately if they occur. TRALI is a potentially life-threatening condition requiring immediate treatment in an intensive care unit.

Effect on laboratory tests

After immunoglobulin administration, there may be a transient increase in the level of various passively transferred antibodies in the patient's blood, which may cause false-positive results in serological tests.

Dosage

Unless otherwise prescribed, the following recommendations should be followed:

Prevention of hepatitis B virus reinfection after liver transplantation due to hepatitis B-related liver failure.

In adults:

10,000 IU on the day of transplantation, perioperatively, followed by 2000-10,000 IU (40-200 ml)/day for 7 days, and as needed to maintain antibody levels above 100-150 IU/l in HBV-negative patients and above 500 IU/l in HBV-positive patients.

In children:

Dosage should be based on body surface area: 10,000 IU/1.73 m².

Hepatitis B prophylaxis:

• Prevention of hepatitis B in non-immunized individuals in case of accidental exposure: At least 500 IU (10 ml), depending on the intensity of exposure, as soon as possible after exposure, preferably within 24-72 hours.
• Hepatitis B prophylaxis in hemodialysis patients:
• 8-12 IU (0.16-0.24 ml)/kg with a maximum dose of 500 IU (10 ml) every 2 months until seroconversion after vaccination.
• Prevention of hepatitis B in newborns whose mothers are hepatitis B virus carriers, at birth or as soon as possible after birth: 30-100 IU (0.6-2 ml)/kg. Administration of hepatitis B immunoglobulin can be repeated until seroconversion after vaccination.

In all these cases, hepatitis B vaccination is recommended.

The first dose of the vaccine should be given on the same day as the hepatitis B immunoglobulin, but in a different part of the body.

In patients who do not respond to hepatitis B vaccination (no measurable hepatitis B antibodies) and require ongoing prophylaxis, 500 IU (10 ml) may be considered in adults and 8 IU (0.16 ml)/kg in children every 2 months; the minimum protective antibody level is considered to be 10 IU/ml.