HepatEct 50 IU/ml solution for infusion

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Hepatect 50 IU/ml solution for infusion

Human hepatitis B immunoglobulin for intravenous administration

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet as 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 and must not be given to other people, even if they have the same symptoms as you, because it could harm them.

• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are effects not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What Hepatect is and what it is used for

Hepatect contains the active substance human hepatitis B immunoglobulin, which can protect you from hepatitis B. Hepatitis B is an inflammation of the liver caused by the hepatitis B virus. Hepatect 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).

Hepatect is used to provide immediate and long-lasting immunity (protection) against:

• Preventing hepatitis B in patients who are not vaccinated or not fully vaccinated against hepatitis B and who are at risk of becoming infected with hepatitis B.
• Preventing liver infection in transplanted livers in patients who test positive for hepatitis B.
• Newborn babies whose mothers are infected with the hepatitis B virus.
• Protecting patients in whom the hepatitis B vaccine has not provided sufficient protection.

2. What you need to know before using Hepatect

Do not use Hepatect,

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

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Hepatect

• if you have not previously received this medicine or if a long time has passed (e.g., several weeks) since your last dose (close monitoring during and for one hour after infusion will be required)

• if you have recently received Hepatect (monitoring will be needed during and for at least 20 minutes after the infusion)

• if you have an untreated infection or an underlying chronic inflammation

• if you have previously experienced a reaction to other antibodies (in rare cases, you may be at risk of an allergic reaction)

• if you have or have had kidney disease

• if you are taking medications that may damage your kidneys (if kidney function worsens, treatment with Hepatect may need to be discontinued)

Special caution will be taken by your doctor if you are overweight, elderly, have diabetes, suffer from hypertension, reduced blood volume (hypovolemia), have abnormally thick blood (elevated blood viscosity), are bedridden or have been immobilized for a prolonged period, or have blood vessel disorders (vascular diseases) or other risk factors for thrombotic events (blood clots).

Remember: Reactions

During the Hepatect infusion, you will be closely monitored for any reactions (e.g., anaphylaxis). Your doctor will ensure that the infusion rate of Hepatect is appropriate for your condition.

If you experience any of the following signs of a reaction—such as headache, flushing, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, or low blood pressure—inform your doctor immediately. The infusion rate may be reduced or the infusion stopped completely.

Information on transmission of infectious agents

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

• careful donor selection to exclude those at risk of carrying infectious diseases,
• testing of individual donations and plasma pools for specific markers of infection,
• inclusion of manufacturing steps designed to inactivate or remove viruses.

Despite these measures, the possibility of transmitting infectious agents cannot be completely ruled out when medicines derived from human blood or plasma are administered. This also applies to emerging or unknown viruses and other types of infections.

These measures 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 effectiveness against non-enveloped viruses, such as hepatitis A virus and parvovirus B19.

Immunoglobulins have not been associated with transmission of hepatitis A virus or parvovirus B19 infections, possibly due to the protective effect of antibodies against these infections present in the medicine.

It is strongly recommended that each time a dose of Hepatect is administered, the name of the medicine and the batch number be recorded to maintain a traceable record of batches used.

Use of Hepatect with other medicines

Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.

Hepatect may reduce the effectiveness of certain vaccines, for example:

• measles vaccine
• rubella vaccine
• mumps vaccine
• varicella vaccine

You may need to wait up to 3 months before receiving certain vaccines, or up to one year before receiving the measles vaccine.

Avoid concomitant use of loop diuretics with Hepatect.

Pregnancy, breastfeeding, and fertility

If you are pregnant, breastfeeding, think you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.

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

Driving and use of machines

The effect of Hepatect on the ability to drive and operate machinery is minimal. However, if you experience adverse reactions during treatment, you should wait until these have resolved before driving or operating machinery.

3. How to use Hepatect

Hepatect is intended for intravenous administration (infusion into a vein). It will be administered by a doctor or nursing staff. The recommended dose will depend on your condition and body weight. Your doctor will determine the appropriate amount to administer.

At the beginning of the infusion, Hepatect will be given at a slow rate. Afterwards, the doctor may gradually increase the infusion rate.

If you have any further questions about the use of this product, ask your doctor or nursing staff.

If you use more Hepatect than you should:

In case of overdose or accidental ingestion, call the Toxicology Information Service immediately at telephone number 915620420.

4. Possible adverse effects

Like all medicines, this medicine may cause adverse effects, although not everyone experiences them.

The following adverse effects have been reported in clinical trials with Hepatect:

Not known: frequency cannot be estimated from available data

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

Normal human immunoglobulin preparations in general may cause the following adverse effects (in decreasing frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate backache
• decreased number of red blood cells due to their destruction in blood vessels (hemolytic reactions [reversible]) and (rarely) hemolytic anemia requiring blood 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 lungs (pulmonary embolism), clots in a vein (deep vein thrombosis)
• cases of acute transient inflammation of the protective membranes covering the brain and spinal cord (aseptic meningitis)
• cases of blood test results indicating kidney dysfunction and/or sudden kidney failure
• cases of transfusion-related acute lung injury (TRALI). This causes accumulation of fluid unrelated to the heart in the air spaces of the lungs (non-cardiogenic pulmonary edema). You may experience significant difficulty in breathing (dyspnea), rapid breathing (tachypnea), abnormally low levels of oxygen in the blood (hypoxia), and increased body temperature (fever).

If any adverse reaction occurs, the infusion rate will be reduced or the infusion stopped.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the Spanish Pharmacovigilance System for Human Medicinal Products: https://www.notificaRAM.es.

By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Hepatect

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

Do not use this medicine after the expiry date stated on the outer packaging and on the label of the vial.

Store the vial in the outer packaging to protect it from light.

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

The solution should be clear or slightly opalescent and colourless to pale yellow. Do not administer solutions that are cloudy or contain deposits.

The solution should be administered immediately after opening the container. The product should be at room temperature or body temperature before administration.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the container and other information

Composition of Hepatect:

• The active substance in Hepatect is human anti-hepatitis B immunoglobulin for intravenous administration.

Hepatect contains 50 mg/ml of human plasma protein, of which at least 96% is immunoglobulin G (IgG). The anti-hepatitis B antibody content is at least 50 IU/ml. The maximum content of immunoglobulin A (IgA) is 2,000 micrograms/ml. The approximate distribution by IgG subclasses is: 59% IgG1, 35% IgG2, 3% IgG3, and 3% IgG4.

• The other components are glycine and water for injectable preparations.

Appearance of the product and contents of the container

Hepatect is a solution for infusion. The solution is transparent or slightly opalescent (milky, opal-like appearance) and colorless or pale yellow.

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

Marketing Authorization Holder and Manufacturer:

Biotest Pharma GmbH

Landsteinerstrasse 5

63303 Dreieich

Germany

Telephone: +49 6103 801-0

Fax: +49 6103 801-150

e-mail: [email protected]

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

Grifols Movaco, S.A.

Can Guasc, s/n – Parets del Vallès

08150 Barcelona

Spain

Date of the most recent review of this leaflet: 06/2025

Detailed and up-to-date information on this medicinal product is available on the website of the Spanish Agency of Medicines and Health Products (AEMPS): http://www.aemps.gob.es/

This information is intended for healthcare professionals only:

Method of administration

Intravenous route

Hepatect must be administered intravenously at an initial infusion rate of 0.1 ml/kg body weight/hour for 10 minutes. If adverse reactions occur, the infusion rate should be reduced or the infusion interrupted. If well tolerated, the infusion rate may be gradually increased up to a maximum of 1 ml/kg body weight/hour.

Clinical experience in newborns of mothers who are carriers of hepatitis B virus has shown that intravenous infusion of Hepatect at a rate of 2 ml over 5 to 15 minutes is well tolerated.

Special precautions

Monitoring of anti-HBs antibody levels:

Serum levels of anti-HBs antibodies should be monitored periodically in patients. The dose should be adjusted to maintain therapeutic antibody levels and to avoid underdosing (see Dosage section).

Particularly when higher doses are used, administration of intravenous human immunoglobulin requires:

• adequate hydration prior to starting immunoglobulin infusion
• monitoring of urine output
• monitoring of serum creatinine levels
• avoidance of concomitant use of loop diuretics

In case of adverse reaction, the infusion rate should be reduced or the infusion stopped. Treatment depends on the nature and severity of the adverse reaction.

Hypersensitivity

Hypersensitivity reactions are rare. Rarely, human anti-hepatitis B immunoglobulin may induce a drop in blood pressure with anaphylactic reaction, even in patients who have previously tolerated immunoglobulin treatments.

Suspicion of an allergic or anaphylactic-type reaction requires immediate discontinuation of the infusion. In case of shock, standard medical guidelines for shock management should be followed.

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

Thromboembolism

There is clinical evidence linking intravenous immunoglobulin (IVIg) administration to thromboembolic events such as myocardial infarction, cerebrovascular accident (including stroke), pulmonary embolism, and deep vein thrombosis. This is presumed to be related to a relative increase in blood viscosity due to the high immunoglobulin load in at-risk patients. Caution should be exercised when prescribing and administering IVIg in obese patients and in patients with pre-existing risk factors for thrombotic events (such as advanced age, hypertension, diabetes mellitus, history of vascular disease or thrombotic episodes, patients with acquired or hereditary thrombophilic disorders, patients with prolonged immobilization, patients with severe hypovolemia, or patients with conditions increasing blood viscosity).

In patients at risk of thromboembolic adverse reactions, IVIg products should be administered at the lowest feasible infusion rate and dose.

Acute renal failure

Cases of acute renal failure have been reported in patients receiving IVIg therapy. In most cases, risk factors have been identified, such as pre-existing renal insufficiency, diabetes mellitus, hypovolemia, obesity, concomitant use of nephrotoxic drugs, or age over 65.

Renal parameters should be evaluated before IVIg infusion, especially in patients considered at higher potential risk of developing acute renal failure, and again at appropriate intervals. In patients at risk of acute renal failure, IVIg products should be administered at the lowest feasible infusion rate and dose. In case of renal failure, discontinuation of IVIg should be considered.

Although reports of renal dysfunction and acute renal failure have been associated with administration of many authorized IVIg products containing various excipients such as sucrose, glucose, and maltose, those containing sucrose as a stabilizer account for a disproportionate number of cases. In at-risk patients, consideration could be given to using human immunoglobulin products that do not contain these excipients. Hepatect does not contain sucrose, maltose, or glucose.

Aseptic Meningitis Syndrome (AMS)

Aseptic meningitis syndrome has been reported in association with IVIg treatment.

The syndrome typically begins several hours to 2 days after IVIg treatment. Cerebrospinal fluid (CSF) studies are frequently positive, showing pleocytosis of up to several thousand cells/mm³, predominantly granulocytic, and elevated protein levels up to several hundred mg/dl.

AMS may occur more frequently with high-dose IVIg treatments (2 g/kg).

Patients presenting with these signs and symptoms should undergo a thorough neurological examination, including cerebrospinal fluid (CSF) studies, to exclude other causes of meningitis.

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

Hemolytic anemia

IVIg products may contain antibodies against blood groups that could act as hemolysins and induce in vivo coating of red blood cells with immunoglobulin, leading to a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia may develop after IVIg treatment due to increased red blood cell sequestration. Clinical signs and symptoms of hemolysis should be monitored in IVIg recipients.

Neutropenia/Leukopenia

A transient decrease in neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported after IVIg treatment. This usually occurs within hours or days after IVIg administration and resolves spontaneously within 7 to 14 days.

Transfusion-Related Acute Lung Injury (TRALI)

Non-cardiogenic acute lung injury (TRALI) has occasionally been reported in patients receiving IVIg. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever, and hypotension. Symptoms of TRALI generally develop during or within 6 hours after infusion, frequently between the first and second hour. Therefore, recipients of IVIg should be closely monitored, and IVIg infusion should be immediately interrupted in case of pulmonary adverse reactions. TRALI is a potentially life-threatening condition requiring immediate treatment in an intensive care unit.

Interference with serological testing

Following immunoglobulin administration, the transient increase in various passively transferred antibodies in the patient's blood may lead to 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-induced liver failure:

In adults:

10,000 IU on the day of transplantation, during the perioperative period,

followed by 2,000–10,000 IU (40–200 ml)/day for 7 days,

and as needed to maintain antibody levels above 100–150 IU/l in HBV-DNA-negative patients and above 500 IU/l in HBV-DNA-positive patients.

In children:

The dosage should be adjusted according to body surface area based on 10,000 IU/1.73 m².

Hepatitis B immunoprophylaxis:

• Prevention of hepatitis B following accidental exposure in non-immunized individuals:

As soon as possible after exposure, preferably within the first 24–72 hours, a minimum of 500 IU (10 ml) should be administered, depending on the intensity of exposure.

• Hepatitis B immunoprophylaxis in hemodialysis patients:

8–12 IU (0.16–0.24 ml)/kg, up to a maximum of 500 IU (10 ml), every 2 months until seroconversion after vaccination.

• Prevention of hepatitis B in newborns of hepatitis B virus carrier mothers at birth or as soon as possible after birth: 30–100 IU (0.6–2 ml)/kg. Anti-hepatitis B immunoglobulin may be administered repeatedly until seroconversion after vaccination.

In all these situations, vaccination against hepatitis B virus is strongly recommended. The first vaccine dose may be administered on the same day as human anti-hepatitis B immunoglobulin, but at a different injection site.

In individuals who do not show an immune response (non-detectable anti-hepatitis B antibodies) after vaccination and who require ongoing prevention, 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 protective antibody titer is considered to be 10 mIU/ml.