Hepatect cp

Package leaflet: Information for the user

Hepatect CP 50 IU/ml, solution for infusion
Human hepatitis B immunoglobulin for intravenous administration
Read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this 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 a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any adverse reactions, including any possible adverse reactions not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

1. What Hepatect CP is and what it is used for
2. What you need to know 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 Hepatect CP is and what it is used for

Hepatect CP contains as the active substance human immunoglobulin against hepatitis B, which provides protection against hepatitis B caused by the hepatitis B virus. Hepatect CP is a solution for intravenous infusion 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) of solution.
Hepatect CP is used to provide immediate and long-lasting immunity (protection):

• for prevention of hepatitis B virus infection in patients who have not been vaccinated against hepatitis B or have not completed the full vaccination cycle and who are at risk of such infection.
• for prevention of hepatitis B infection in liver transplant recipients who test positive for hepatitis B virus.
• for newborns whose mothers are infected with hepatitis B virus.
• for patients in whom the hepatitis B vaccine has not provided effective protection.

2. Important information before using Hepatect CP

When not to use Hepatect CP

• if the patient is allergic to human immunoglobulin or to any of the other ingredients of this medicine (listed in section 6).
• if the patient has immunoglobulin A (IgA) deficiency, especially if antibodies against IgA are present in the blood, as this may lead to anaphylaxis.

Warnings and precautions
Before starting Hepatect CP, discuss with the doctor, pharmacist, or nurse if

• the patient has not previously received this medicine or if there has been a long interval (e.g. several weeks) since the last dose (the patient must be closely monitored during and for one hour after the infusion)
• the patient has recently received Hepatect CP (the patient must be observed during and for at least 20 minutes after the infusion)
• the patient has an untreated infection or a coexisting chronic inflammatory condition
• the patient has had a reaction to other antibodies (in rare cases, there is a risk of allergic reactions)
• the patient has or has had kidney disease
• the patient is taking medicines that may damage the kidneys (if kidney function worsens, treatment with Hepatect CP may need to be discontinued)

Special precautions should be taken by the doctor in patients who are overweight, elderly, have diabetes or high blood pressure, have low blood volume (hypovolemia), increased blood viscosity (high blood viscosity), are immobilized, have vascular disorders, or have other risk factors for thrombotic events (blood clots).

Note – Reactions
The patient will be closely observed during administration of Hepatect CP to ensure that no adverse reactions occur (e.g. anaphylaxis). The doctor will check whether the infusion rate is appropriate for the patient.
If any of the following reactions occur during infusion of Hepatect CP—such as headache, sudden feeling of warmth, chills, muscle pain, wheezing, rapid heartbeat, back pain, nausea, or low blood pressure—inform the doctor immediately.
The infusion rate may be reduced or the infusion stopped completely.

Information on transmission of infectious agents
Hepatect CP is manufactured from human plasma (the liquid part of blood).
For medicines produced from human blood or plasma, specific measures are taken to prevent transmission of infections to patients. These include:

• careful selection of blood and plasma donors to exclude those who may be carriers of infections.
• testing of individual blood donations and pooled plasma samples to detect the presence of viruses/infections.
• inclusion of steps in the manufacturing process designed to inactivate or remove viruses.

Despite these measures, it cannot be completely excluded that medicines prepared from human blood or plasma may transmit infection, including unknown or newly emerging viruses or 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 effectiveness of these measures may be limited against non-enveloped viruses, such as hepatitis A virus and parvovirus B19.
No cases of transmission of hepatitis A or parvovirus B19 have been associated with immunoglobulins, probably because the antibodies against these infections contained in this product provide protective effects.
It is strongly recommended that, each time a dose of Hepatect CP is administered, the product name and batch number be recorded to document the batches used.

Hepatect CP and other medicines
Inform the doctor or pharmacist about all medicines currently being taken, recently taken, or planned to be taken.
Hepatect CP may reduce the effectiveness of certain vaccines, such as those against:

• measles,
• rubella,
• mumps,
• varicella (chickenpox).

It may be necessary to wait up to three months before receiving certain vaccines and up to one year before receiving the measles vaccine.

Concomitant use of loop diuretics with Hepatect CP should be avoided.

Pregnancy, breastfeeding, and fertility
During pregnancy, while breastfeeding, or if pregnancy is suspected or planned, consult a doctor or pharmacist before using this medicine.
The doctor will decide whether Hepatect CP can be used during pregnancy and breastfeeding.

Driving and operating machinery
Hepatect CP has minor influence on the ability to drive and operate machinery. If the patient experiences any adverse reactions during treatment, they should wait until these subside before driving or operating machinery.

3. How to use Hepatect CP

Hepatect CP is intended for intravenous administration (intravenous infusion). It is administered to the patient by a doctor or nurse. The recommended dose depends on the patient's health condition and body weight. The doctor will decide the amount to be administered.
Initially, Hepatect CP is given slowly. The doctor may gradually increase the infusion rate.
Please consult your doctor or nurse if you need advice or further information.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions have been reported spontaneously for Hepatect CP:
Frequency unknown: frequency cannot be estimated from the available data

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

Preparations of human normal immunoglobulin may cause the following adverse reactions
(in decreasing order of frequency):

• chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, joint pain, low blood pressure, and moderate lower back pain
• reduction in red blood cells due to their breakdown within blood vessels ((reversible) hemolytic reactions) and (rarely) hemolytic anemia requiring transfusion
• (rarely) sudden drop in blood pressure and, in sporadic cases, anaphylactic shock
• (rarely) transient skin reactions (including cutaneous lupus erythematosus – frequency unknown)
• (very rarely) thromboembolic reactions, such as myocardial infarction, stroke, blood clots in lung vessels (pulmonary embolism), blood clots in veins (deep vein thrombosis)
• cases of transient acute inflammation of the protective membranes covering the brain and spinal cord (reversible aseptic meningitis)
• cases of blood test results indicating kidney function disorders and (or) acute kidney failure
• cases of acute transfusion-related lung injury (TRALI). This leads to non-cardiac accumulation of fluid in the air spaces of the lungs (non-cardiogenic pulmonary edema). The patient will develop severe breathing difficulties (respiratory distress syndrome), rapid breathing (tachypnea), abnormally low oxygen levels in the blood (hypoxia), and elevated body temperature (fever).

If adverse reactions occur, the infusion rate will be reduced or the infusion will be stopped.
Reporting of adverse reactions
If any adverse effects occur, including any adverse effects not listed in this leaflet, inform your doctor, pharmacist, or nurse. Adverse reactions can be reported directly to:
Department of Monitoring of Adverse Drug Reactions
Office for Registration 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
Website: https://smz.ezdrowie.gov.pl
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Hepatect CP

Keep the medicine out of 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 packaging to protect from light.
Store in a refrigerator (2–8 °C). Do not freeze.
The solution should be clear or slightly opalescent, colourless or pale yellow. Do not use solutions that are cloudy or contain particulate matter.
The solution should be administered immediately after opening the packaging. Before administration, warm the product to room temperature or body temperature.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Hepatect CP contains

• The active substance in 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 hepatitis B antibody content is at least 50 IU/ml. The maximum immunoglobulin A (IgA) content is 2000 micrograms/ml. The approximate distribution of IgG subclasses is as follows: 59% IgG1, 35% IgG2, 3% IgG3 and 3% IgG4.
• The other ingredients are glycine and water for injections.

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 opal appearance), colorless to pale yellow.
Pack sizes: 1 vial containing 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
E-mail: [email protected]

Information intended exclusively for healthcare professionals:

Route of administration
Intravenous administration
Hepatect CP must be administered intravenously at an initial rate of 0.1 ml/kg body weight/hour for 10 minutes. If an adverse reaction occurs, the infusion rate should be reduced or the infusion discontinued. If the product is well tolerated, the infusion rate may be gradually increased to a maximum rate of 1 ml/kg body weight/hour.
Clinical experience in newborns whose mothers were hepatitis B virus carriers has shown that Hepatect CP, administered intravenously at a dose of 2 ml over 5 to 15 minutes, is well tolerated.

Special precautions
Monitoring of anti-HBs antibody levels
Patients should be monitored regularly for serum anti-HBs antibody levels. Dosing should be adjusted to maintain therapeutic antibody levels and to avoid underdosing (see Dosage).

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

• adequate hydration prior to the initiation of human immunoglobulin infusions,
• monitoring of urine output,
• monitoring of serum creatinine concentration,
• avoidance of concomitant use of loop diuretics.

If an adverse reaction occurs, the infusion rate should be reduced or the infusion stopped. Required treatment depends on the type and severity of the adverse reaction.

Hypersensitivity
Hypersensitivity reactions are rare. Human hepatitis B immunoglobulin may rarely cause hypotension with anaphylactic reaction, even in patients who previously tolerated immunoglobulin treatment well.
Suspicion of allergic or anaphylactic-type reactions requires immediate discontinuation of the infusion. In case of shock, standard medical management for shock treatment should be initiated.

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

Thromboembolic complications
There is clinical evidence of an association between IVIg administration and thromboembolic events such as myocardial infarction, cerebrovascular incident (including stroke), pulmonary embolism, and deep vein thrombosis, which are believed to be related to relative increase in blood viscosity due to high immunoglobulin load in patients with risk factors. Caution should be exercised when prescribing and administering IVIg infusions to obese patients and to patients with pre-existing risk factors for thromboembolic events (such as advanced age, hypertension, diabetes, vascular disease or history of thromboembolic events, patients with acquired or inherited thrombophilic conditions, long-term immobilized patients, patients with severe hypovolemia, and patients with conditions affecting increased blood viscosity).
In patients with existing risk of thromboembolic adverse events, IVIg products should be administered at the lowest possible infusion rate and at the lowest possible dose.

Acute renal failure
Cases of acute renal failure have been reported in patients receiving IVIg therapy.
In most cases, risk factors were identified, such as pre-existing renal insufficiency, diabetes, hypovolemia, overweight, concomitant use of nephrotoxic medicinal products, or age over 65.
Renal parameters should be assessed before IVIg infusion and subsequently at appropriate intervals, especially in patients with potential increased risk of acute renal failure. In patients with existing risk of acute renal failure, IVIg products should be administered at the lowest possible infusion rate and at the lowest possible dose. If renal function abnormalities occur, discontinuation of intravenous immunoglobulins should be considered.
Cases of renal dysfunction and acute renal failure have been observed after administration of several registered IVIg products containing various excipients such as sucrose, glucose, and maltose, with sucrose-containing products accounting for the majority of such cases.
In patients at risk, use of human immunoglobulin products not containing these excipients may be considered. Hepatect CP does not contain sucrose, maltose, or glucose.

Aseptic Meningitis Syndrome (AMS)
Aseptic meningitis syndrome has been reported in association with IVIg therapy.
The syndrome usually appears within several hours to 2 days after IVIg treatment. Cerebrospinal fluid analysis often reveals pleocytosis up to several thousand cells/mm³, predominantly granulocytes, and elevated protein concentration up to several hundred mg/dl.
AMS may occur more frequently with high-dose IVIg therapy (2 g/kg).
Patients presenting with such objective and subjective symptoms should undergo thorough neurological evaluation, including cerebrospinal fluid examination, to exclude other causes of meningitis.
Discontinuation of IVIg therapy resulted in resolution of AMS within a few days without sequelae.

Hemolytic anemia
IVIg products may contain blood group antibodies that can act as hemolysins and cause in vivo coating of red blood cells with immunoglobulins, leading to a positive direct antiglobulin reaction (Coombs test), and rarely hemolysis. Hemolytic anemia may occur after IVIg therapy due to intense sequestration of red blood cells. Patients receiving IVIg should be monitored for clinical signs and symptoms of hemolysis.

Neutropenia/leukopenia
Transient decreases in neutrophil count and/or episodes of neutropenia, sometimes severe, have been reported after IVIg therapy. These usually occur within hours or days after administration and resolve spontaneously within 7–14 days.

Transfusion-Related Acute Lung Injury (TRALI)
Acute non-cardiogenic pulmonary edema (TRALI) has been reported in patients receiving IVIg. TRALI is characterized by severe hypoxia, dyspnea, rapid breathing, cyanosis, fever, and hypotension. TRALI symptoms typically occur during or within 6 hours of infusion, often within 1–2 hours. Therefore, patients receiving IVIg should be monitored for pulmonary adverse reactions, and infusion should be immediately discontinued if such reactions occur. TRALI is a potentially life-threatening condition requiring immediate treatment in an intensive care setting.

Effect on serological test results
Following immunoglobulin administration, transient increases in various passively transferred antibodies in the patient's blood may occur, which can lead to false-positive serological test results.

Dosage
If not otherwise prescribed, the following recommendations should be followed:

Prevention of hepatitis B virus reinfection after liver transplantation due to liver failure caused by hepatitis B
In adults:
10,000 IU on the day of transplantation, perioperatively,
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-negative patients and above 500 IU/l in HBV-positive patients.

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

Immunoprophylaxis of hepatitis B:

• Prevention of hepatitis B following accidental exposure in non-immunized individuals: At least 500 IU (10 ml), depending on the intensity of exposure, as soon as possible after exposure, preferably within 24–72 hours.
• Immunoprophylaxis of hepatitis B 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 of mothers who are hepatitis B virus carriers: 30–100 IU (0.6–2 ml)/kg at birth or as early as possible thereafter. Administration of hepatitis B immunoglobulin may be repeated until seroconversion after vaccination.

In all these cases, hepatitis B vaccination is recommended.
The first vaccine dose should be administered on the same day as hepatitis B immunoglobulin, but at a different injection site.

In patients who do not show an immune response after vaccination (no detectable hepatitis B antibodies) and in whom ongoing disease prevention is required, administration of 500 IU (10 ml) in adults and 8 IU (0.16 ml)/kg in children every 2 months may be considered; a minimum protective antibody titer is considered to be 10 mIU/ml.