Human hepatitis B Immunoglobulin.
Human hepatitis B immunoglobulin: See Table 1.
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Distribution of IgG subclasses: IgG1
: 63.7%, IgG2
: 31.8%, IgG3
: 3.3%; IgG4
Maximum content of IgA 300 micrograms/ml.
Sodium content: 3.9 mg/ml (0.170 mmol/ml).
The solution is clear or slightly opalescent, colourless or pale-yellow or light-brown; during storage it may show formation of slight turbidity or a small amount of particulate matter.
Glycine, Sodium chloride, Water for injections.
Pharmacotherapeutic Group: Immune sera and immunoglobulins. Human hepatitis B immunoglobulin. ATC Code: J06BB04.
Pharmacology: Pharmacodynamics: Human hepatitis B immunoglobulin contains mainly immunoglobulin G (IgG) with a specifically high content of antibodies against hepatitis B virus surface antigen (HBs).
A study carried out in HBsAg negative subjects liver transplanted after infection of HBV, proved the efficacy of IMMUNOHBs in maintaining the levels of anti HBsAg antibodies above 100 IU/l. In this study IMMUNOHBs was administered with doses of 2000-2160 IU (according to the pack size), every 15 days for a period of six months.
The average of the levels of anti HBsAg antibodies, measured before each of the 12 administrations, were above the considered threshold (403 IU/l for concentration 180 IU/ml with a minimum level of 106 IU/l).
Paediatric population: Published data related to efficacy and safety studies have not revealed major differences between adults and children suffering from the same disorder.
Pharmacokinetics: Human hepatitis B immunoglobulin for intramuscular use is bioavailable in the recipient's circulation after a delay of 2-3 days.
Human hepatitis B immunoglobulin has a half-life of about 3-4 weeks. This half-life may vary from patient to patient.
IgG and IgG-complexes are broken down in the reticuloendothelial system.
Toxicology: Preclinical Safety Data: Immunoglobulins are normal constituents of the human body. Moreover, as administration of immunoglobulins in animal studies may lead to the formation of antibodies, preclinical safety data are limited. However, the limited animal studies did not show special risks for humans, based on acute and sub-acute toxicity studies.
Prevention of hepatitis B virus re-infection after liver transplantation for hepatitis B induced liver failure.
Immunoprophylaxis of hepatitis B: In case of accidental exposure in non-immunised subjects (including persons whose vaccination is incomplete or status unknown).
In haemodialysed patients, until vaccination has become effective.
In the newborn of a hepatitis B virus carrier-mother.
In subjects who did not show an immune response (no measurable hepatitis B antibodies) after vaccination and for whom a continuous prevention is necessary due to the continuous risk of being infected with hepatitis B.
Prevention of hepatitis B virus re-infection after liver transplantation for hepatitis B induced liver failure: Adults: 2000 IU every 15 days.
For the long term treatment the dosage should be aimed to the maintenance of the serum level of anti HBsAg antibodies above 100 IU/l in HBV-DNA negative patients and above 500 IU/l in HBV-DNA positive patients.
Paediatric population: There are no available data regarding the efficacy in paediatric population.
Immunoprophylaxis of hepatitis B: Prevention of hepatitis B in case of accidental exposure in non-immunised subjects: at least 500 IU, depending on the intensity of exposure, as soon as possible after exposure, and preferably within 24-72 hours.
Immunoprophylaxis of hepatitis B in haemodialysed patients: 8-12 IU/kg with a maximum of 500 IU, every 2 months until seroconversion following vaccination.
Prevention of hepatitis B in the newborn, of a hepatitis B virus carrier-mother, at birth or as soon as possible after birth: 30-100 IU/kg. The hepatitis B immunoglobulin administration may need to be repeated until seroconversion following vaccination.
In all these situations, vaccination against hepatitis B virus is highly recommended. The first vaccine dose can be injected the same day as human hepatitis B immunoglobulin, however in different sites.
In subjects who did not show an immune response (no measurable hepatitis B antibodies) after vaccination, and for whom continuous prevention is necessary, administration of 500 IU to adults and 8 IU/kg to children every 2 months can be considered; a minimum protective antibody titre is considered to be 10 mIU/ml.
Method of administration: IMMUNOHBs should be administered via the intramuscular route.
If a large volume (>2 ml for children or >5 ml for adults) is required, it is recommended to administer this in divided doses at different sites.
When simultaneous vaccination is necessary, the immunoglobulin and the vaccine should be administered at two different sites.
Consequences of overdose are not known.
Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to human immunoglobulins.
Ensure that IMMUNOHBs is not administered into a blood vessel, because of the risk of shock.
If the recipient is a carrier of HBsAg, there is no benefit in administering this product.
True hypersensitivity reactions are rare.
IMMUNOHBs contains a small quantity of IgA. Individuals who are deficient in IgA have the potential for developing IgA antibodies and may have anaphylactic reactions after administration of blood components containing IgA. The physician must therefore weigh the benefit of treatment with IMMUNOHBs against the potential risk of hypersensitivity reactions.
Rarely, human hepatitis B immunoglobulin can induce a fall in blood pressure with anaphylactic shock, even in patients who have tolerated previous treatment with immunoglobulins.
Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the injection. In case of shock, standard medical treatment for shock should be implemented.
The product contains 3.9 mg sodium per ml. Depending on the total dose required, this should be taken into consideration in patients on a controlled sodium diet.
Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses.
Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.
The measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV and for the non-enveloped viruses such as HAV.
The measures taken may be of limited value against non-enveloped viruses such as parvovirus B19.
There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.
It is strongly recommended that every time that IMMUNOHBs is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
Interference with serological testing: After injection of immunoglobulin the transitory rise of the various passively transferred antibodies in the patient's blood may result in misleading positive results in serological testing.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies, for example the antiglobulin test (Coombs' test).
Effects on the ability to drive and use machines: IMMUNOHBS does not affect the ability to drive and use machines.
Fertility: Clinical experience with immunoglobulins shows that no harmful effects on fertility are to be expected.
Use in Children: No specific measures or monitoring are required for the paediatric population.
Pregnancy: The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials and therefore it should be used with caution in pregnant women or breast-feeding mothers. Clinical experience with immunoglobulins shows that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.
Lactation: Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.
The table presented as follows is according to the MedDRA system organ classification (SOC and Preferred Term Level).
Frequencies have been evaluated according to the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
There are no robust data on the frequency of undesirable effects from clinical trials. The following undesirable effects have been reported: See Table 2.
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For safety with respect to transmissible agents, see Precautions.
Frequency, type and severity of adverse reactions in children are not expected to be different from those of adult population.
Reporting of suspected adverse reactions:
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Live attenuated virus vaccines: Immunoglobulin administration may interfere with the development of an immune response to live attenuated virus vaccines such as rubella, mumps, measles and varicella for a period of 3 months.
After administration of this product, an interval of at least 3 months should elapse before vaccination with live attenuated virus vaccines.
Human hepatitis B immunoglobulin should be administrated three to four weeks after vaccination with such a live attenuated vaccine; in case administration of human hepatitis B immunoglobulin is essential within three to four weeks after vaccination, then revaccination should be performed three months after the administration of human hepatitis B immunoglobulin.
Instructions for use and handling and disposal: The product should be brought to room or body temperature before use.
Vials: Remove the central protection from the rubber stopper and draw the solution with an injection syringe. Change the needle and inject.
Once the solution is withdrawn from the container into the syringe, the medicinal product must be administered immediately.
Attention: The injection must be carried out after having ensured that a blood vessel has not been penetrated.
The solution is clear or slightly opalescent, colourless or pale-yellow or light-brown. Do not use solutions which are cloudy or have deposits.
Any unused product or waste material should be disposed in accordance with local requirements.
Incompatibilities: IMMUNOHBs must not be mixed with other medicinal products.
Store in a refrigerator at temperature between +2°C and +8°C.
Do not freeze.
Shelf-Life: 3 years.
Once opened the container, the medicinal product should be administered immediately.
J06BB04 - hepatitis B immunoglobulin ; Belongs to the class of specific immunoglobulins. Used in passive immunizations.
Inj (vial) (clear or slightly opalescent, colourless or pale-yellow or light brown) 180 IU x 1 mL. 540 IU x 3 mL.