Prospect: information for the user

Hepatect 50 UI/ml solution for perfusion

Human anti-hepatitis B immunoglobulin for intravenous administration

Read this prospect carefully before starting to use this medication, as it contains important information for you.

• Keep this prospect, as you may need to read it again.

• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medication has been prescribed only to you and should not be given to others, even if they have the same symptoms as you, as it may harm them.
• If you experience adverse effects, consult your doctor, pharmacist, or nurse, even if they do not appear in this prospect. See section 4.

1.What is Hepatect and for what it is used

2.What you need to know before starting to use Hepatect

3.How to use Hepatect

4.Possible adverse effects

5.Storage of Hepatect

6.Contents of the package and additional information

Hepatect contains the active ingredient human anti-hepatitis B immunoglobulin, which may protect you from hepatitis B. Hepatitis B is an inflammation of the liver caused by the hepatitis B virus. Hepatect is a perfusion solution (given through a vein) and is available in vials with 2 ml (100 international units [UI]), 10 ml (500 UI), 40 ml (2000 UI), and 100 ml (5000 UI).

Hepatect is used to provide immediate and prolonged immunity (protection) for:

-Preventing hepatitis B in patients who are not vaccinated or not fully vaccinated against hepatitis B and are at risk of hepatitis B infection.

-Preventing liver infection in transplant patients who test positive for hepatitis B.

-Newborns whose mothers are infected with the hepatitis B virus.

-Protecting patients for whom the hepatitis B vaccine has not provided sufficient protection.

No use Hepatect,

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

-if you have a deficiency of immunoglobulin A (IgA), particularly if you have antibodies against IgA in your blood, as this may lead to anaphylaxis.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting to use Hepatect

• if you have not received this medicine before or if it has been a long time (e.g., several weeks) since you last received it (you will require close monitoring during infusion and for at least one hour after it has finished)

• if you have recently received Hepatect (you will need observation during infusion and for at least 20 minutes after infusion)

• if you have an untreated infection or underlying chronic inflammation

• if you have had 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 have received medicines that can damage your kidneys (if kidney function worsens, treatment with Hepatect may need to be suspended)

Your doctor will take special care if you are overweight, elderly, have diabetes or hypertension, have decreased blood volume (hypovolemia), if your blood is thicker than normal (elevated blood viscosity), are bedridden or have been immobile for some time (immobilization), or have vascular problems (vascular diseases) or other risks of thrombotic episodes (blood clots).

Remember: reactions

During the infusion period with Hepatect, you will be closely monitored to ensure that you do not experience any reaction (e.g., anaphylaxis). Your doctor will ensure that the infusion rate of Hepatect is appropriate for your case.

If you notice any of the following signs of a reaction, i.e., headache, palpitations, chills, muscle pain, wheezing, rapid heart rate, lower back pain, nausea, hypotension during Hepatect infusion, inform your doctor immediately. The infusion rate may be reduced or stopped completely.

Information on transmission of infectious agents

When administering medicines derived from human plasma or blood, certain measures must be taken to prevent infections from being passed to patients. Such measures include:

• a careful selection of donors, to exclude those who are at risk of being carriers of infectious diseases,
• analysis of specific infection markers in individual donations and plasma mixtures,
• the inclusion of stages in the manufacturing process to eliminate/inactivate viruses.

Despite this, when administering medicines derived from human blood or plasma, the possibility of transmission of infectious agents cannot be ruled out completely. This also applies to emerging or unknown viruses or other types of infections.

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

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

Immunoglobulins have not been associated with transmission of infections by hepatitis A virus or parvovirus B19, possibly due to the protective effect of the 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 batch number administered be recorded in order to maintain a record of the batches used.

Use of Hepatect with other medicines

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

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

-measles vaccine

-rubella vaccine

-mumps vaccine

-chickenpox vaccine

You may need to wait 3 months before receiving certain vaccines or up to a year for measles vaccination.

Avoid concomitant use of loop diuretics with Hepatect.

Pregnancy, breastfeeding and fertility

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

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

Driving and operating machinery

The influence of Hepatect on your ability to drive and operate machinery is small. If you experience adverse reactions during treatment, you should wait until they resolve before driving or operating machinery.

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. The doctor will know the appropriate amount to administer to you.

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

If you have any other 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, phone 915620420.

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

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

Unknown: the frequency cannot be estimated from the available data

-severe allergic reactions (anaphylactic shock)

-hypersensitivity reactions

-headache

-dizziness

-rapid heart rate (tachycardia)

-low blood pressure (hypotension)

-nausea

-skin reactions (cutaneous), such as rash, itching

-fever

-uncomfortable feeling

Human normal immunoglobulin preparations in general may cause the following side effects (in decreasing frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate back pain
• decrease in the number of red blood cells due to their destruction in blood vessels (reversible hemolytic reactions) 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, unknown frequency)
• (very rarely) thromboembolic reactions such as heart attack (myocardial infarction), stroke, pulmonary embolism, deep vein thrombosis
• cases of acute transient inflammation of the protective membranes that cover the brain and spinal cord (aseptic spinal meningitis)
• cases of abnormal blood test results indicating renal dysfunction and/or sudden kidney failure
• cases of acute lung injury related to transfusion (TRALI). This causes the accumulation of non-cardiogenic fluid in the lung airspaces (pulmonary edema). You may experience significant difficulty breathing (dyspnea), rapid breathing (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and increased body temperature (fever).

If any side effect occurs, the infusion rate will be reduced or discontinued.

Reporting of side effects

Ifyou experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through theSpanish System for Pharmacovigilance of Medicines for Human Use:https://www.notificaram.es.

By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the outer packaging and on the vial label.

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

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

The solution must be transparent or slightly opalescent and colorless to pale yellow. Do not administer solutions that are turbid or have deposits.

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

Medications should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Hepatect:

-The active principle of 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 content of anti-hepatitis B antibodies is 50 IU/ml. The maximum content of immunoglobulin A (IgA) is 2,000 micrograms/ml. The approximate distribution by subclasses of IgG is: 59% of IgG1, 35% of IgG2, 3% of IgG3, and 3% of IgG4.

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

Aspect of the product and content of the package:

Hepatect is a perfusion solution. The solution is transparent or slightly opalescent (opal-like milky color) and colorless or pale yellow.

Package size: 1 vial with 2 ml, 10 ml, 40 ml, or 100 ml of solution.

Holder of the marketing authorization and responsible for manufacturing:

Biotest Pharma GmbH

Landsteinerstrasse 5

63303 Dreieich

Germany

Phone: + 49 6103 801-0

Fax: + 49 6103 801-150

Email: [email protected]

For more information about this medication, please contact the local representative of the marketing authorization holder:

Grifols Movaco, S.A.

Can Guasc, s/n – Parets del Vallès

08150 Barcelona

Spain

Last review date of this leaflet: 11/2019

The detailed and updated information about this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

This information is intended solely for healthcare professionals:

Administration form:

Intravenous

Hepatect should be perfused intravenously at an initial rate of 0.1 ml/kg of body weight/hour for 10 minutes. In case of adverse reactions, the rate of administration will be reduced or the perfusion will be interrupted. If well tolerated, the rate of administration can be gradually increased to a maximum of 1 ml/kg of body weight/hour.

Experience with newborns of mothers carrying the hepatitis B virus has shown that intravenous perfusion of Hepatect at a rate of 2 ml in 5 to 15 minutes is well tolerated.

Special precautions:

Monitoring of anti-HBs antibody levels::

Patients' serum anti-HBs antibody levels should be monitored periodically. The dose should be adjusted to maintain therapeutic levels of antibodies and to avoid underdosing (see the Posology section).

Especially when administered at higher doses, intravenous immunoglobulin administration requires:

• Adequate hydration before starting the perfusion of immunoglobulins

• Monitoring of diuresis

• Monitoring of serum creatinine levels

• Avoiding concomitant use of loop diuretics

In case of adverse reactions, the rate of perfusion will be reduced or the perfusion will be interrupted. Treatment depends on the nature and intensity of the adverse reaction.

Hypersensitivity:

Reactions of hypersensitivity are rare. Rarely, human anti-hepatitis B immunoglobulin may induce a drop in blood pressure with anaphylactic reaction, even in patients who have tolerated previous treatments with immunoglobulin.

Suspicion of an allergic or anaphylactic reaction requires immediate suspension of perfusion. In case of shock, standard medical guidelines for shock treatment should be followed.

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

Thromboembolism:

Clinical evidence suggests an association between IVIg administration and the occurrence of thromboembolic events, such as myocardial infarction, stroke (including cerebral infarction), pulmonary embolism, and deep vein thrombosis, which is believed to be related to an increase in blood viscosity due to the high flow of immunoglobulin 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, 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, IVIg products should be administered at the lowest practicable 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 medications, or age over 65.

Before IVIg perfusion, renal parameters should be evaluated, especially in patients considered to be at higher 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 practicable rate and dose. In case of renal failure, IVIg perfusion should be considered for suspension.

Although reports of renal dysfunction and acute renal failure have been associated with the administration of many IVIg products authorized, which contain various excipients such as saccharose, glucose, and maltose, those containing saccharose as a stabilizer are disproportionately represented within the total number. In at-risk patients, the use of IVIg products that do not contain these excipients may be considered. Hepatect does not contain saccharose, maltose, or glucose.

Asymptomatic aseptic meningitis (AAM):

Aseptic meningitis has been reported in association with IVIg treatment.

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

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

Patients showing these signs and symptoms should undergo an exhaustive neurological examination, including cerebrospinal fluid studies (CSF), to exclude other causes of meningitis.

Suspension of IVIg treatment has resulted in the resolution of AAM 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. Vigilance for clinical signs and symptoms of hemolysis in IVIg recipients is recommended.

Neutropenia/Leucocytopenia:

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

Transfusion-related acute lung injury (TRALI):

In some cases, TRALI has been reported in patients who have received IVIg. TRALI is characterized by severe hypoxia, dyspnea, tachypnea, cyanosis, fever, and hypotension. Symptoms of TRALI usually develop during or within 6 hours of perfusion, often between the first and second hour. Therefore, IVIg recipients should be monitored, and perfusion of IVIg should be interrupted immediately in case of pulmonary adverse reactions. TRALI is a potentially fatal condition that should be treated immediately in the intensive care unit.

Interference with serological tests:

After immunoglobulin administration, the transient increase in various transferred antibodies in the patient's blood may cause false-positive results in serological tests.

Posology:

Unless otherwise prescribed, the following recommendations should be followed:

Prevention of hepatitis B reinfection after liver transplantation due to hepatitis B-induced liver insufficiency:

In adults:

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

Continuing with 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 patients with negative ADN-VHB and above 500 IU/l in those with positive ADN-VHB.

In children:

The dosage will be adjusted based on body surface area, using 10,000 IU/1.73 m².

Immunoprophylaxis of hepatitis B:

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

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

- Immunoprophylaxis of hepatitis B in patients on hemodialysis:

8-12 IU (0.16-0.24 ml)/kg with a maximum of 500 IU (10 ml) every 2 months until seroconversion occurs after vaccination.

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

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

In subjects who did not show an immune response (undetectable anti-hepatitis B antibodies) after vaccination and who require continued 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 mUI/ml.