- 1. Name of the medicinal product
- 2. Qualitative and quantitative composition
- 3. Pharmaceutical form
- 4. Clinical particulars
- 4.1 Therapeutic indications
- 4.2 Posology and method of administration
- 4.3 Contraindications
- 4.4 Special warnings and precautions for use
- 4.5 Interaction with other medicinal products and other forms of interaction
- 4.6 Pregnancy and lactation
- 4.7 Effects on ability to drive and use machines
- 4.8 Undesirable effects
- 4.9 Overdose
- 5. Pharmacological properties
- 5.1 Pharmacodynamic properties
- 5.2 Pharmacokinetic properties
- 5.3 Preclinical safety data
- 6. Pharmaceutical particulars
- 6.1 List of excipients
- 6.2 Incompatibilities
- 6.3 Shelf life
- 6.4 Special precautions for storage
- 6.5 Nature and contents of container
- 6.6 Special precautions for disposal and other handling
- 7. Marketing authorisation holder
- 8. Marketing authorisation number(s)
- 9. Date of first authorisation/renewal of the authorisation
- 10. Date of revision of the text
1. Name of the medicinal product
Human Hepatitis B Immunoglobulin, 100 IU/mL sterile solution
2. Qualitative and quantitative composition
Human Hepatitis B Immunoglobulin contains human protein, 10-100 g/L, of which at least 95% is IgG. The concentration of specific IgG to hepatitis B virus is 100 IU/mL in nominal 200 IU and 500 IU vials. The correct volume to give the stated potency is overprinted on the label.This product is prepared from plasma from screened donors. Donors are selected from the USA. For excipients, see section 6.1.
3. Pharmaceutical form
Solution for injection.
4. Clinical particulars
4.1 Therapeutic indications
Immunoprophylaxis of hepatitis B - In case of accidental exposure e.g. skin pricks, contamination of abrasions, spillage into eye or mouth, bites or scratches, 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 (if birthweight ≤1,500g irrespective of e-antigen status of mother; if >1,500g irrespective of mother's HBeAg status but not necessary if she is known to be anti-HBe positive). - In subjects who did not show an immune response (<10 IU/L of hepatitis B antibodies) after vaccination and for whom a continuous prevention is necessary due to the continuous risk of being infected with hepatitis B. - Sexual contacts of patients with acute hepatitis B within one week of last contact. - Sexual contacts of newly diagnosed chronic hepatitis B if unprotected contact within the last week.
4.2 Posology and method of administration
Posology- Prevention of hepatitis B in case of accidental exposure in non-immunised subjects or in subjects who have had no more than a single dose of vaccine: At least 500 IU, depending on the intensity of exposure, as soon as possible after exposure, and preferably within 24 72 hours, although it should still be considered up to a week after exposure. If it is uncertain whether the source of the exposure is HBsAg positive the prophylactic used of Human Hepatitis B Immunoglobulin is regarded as unnecessary. - Prevention of hepatitis B in case of accidental exposure in subjects or in subjects who have had not responded to a prior, full course of vaccination: At least 500 IU (age 10 years or older), depending on the intensity of exposure, as soon as possible after exposure, and preferably within 24 72 hours, although it should still be considered up to a week after exposure. The dose for children is as follows: 300 IU aged 5 9 years (inclusive); 200 IU aged 0-4 years (inclusive). Irrespective of whether the source of the exposure is known or unknown to be HBsAg positive, a second injection of Human Hepatitis B Immunoglobulin should be given one month later. - 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 carrier-mother, at birth or as soon as possible after birth, preferably within 24 hours of 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 administrationHuman Hepatitis B Immunoglobulin should be administered via the intramuscular route. The usual recommended site for adults is the deltoid; for infants the lateral aspect of the thigh is preferable. 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. If intramuscular administration is contraindicated (bleeding disorders), the injection can be administered subcutaneously if no intravenous product is available. However, it should be noted that there are no clinical efficacy data to support administration by the subcutaneous route.
Hypersensitivity to any of the components. Hypersensitivity to human immunoglobulins.
4.4 Special warnings and precautions for use
Ensure that Human Hepatitis B Immunoglobulin 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 allergic reactions to Human Hepatitis B Immunoglobulin are rare. Human Hepatitis B Immunoglobulin 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 Human Hepatitis B Immunoglobulin against the potential risk of hypersensitivity reactions. Rarely, human hepatitis B immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who have tolerated previous treatment with human immunoglobulin. 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.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. The measures taken may be of limited value against non-enveloped viruses such as HAV and 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 Human Hepatitis B Immunoglobulin 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.
4.5 Interaction with other medicinal products and other forms of interaction
Live attenuated virus vaccinesImmunoglobulin 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 administered three to four weeks after vaccination with such a live attenuated virus vaccine; in case administration of hepatitis B immunoglobulin is essential within three to four weeks after vaccination, then revaccination should be performed three to four months after the administration of Human Hepatitis B Immunoglobulin.
Interference with serological testingAfter 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).
4.6 Pregnancy and lactation
The safety of this medicinal product for use in human pregnancy has not been established in controlled clinical trials. Clinical experience with immunoglobulins suggests that no harmful effects on the course of pregnancy, or on the foetus and the neonate are to be expected.
4.7 Effects on ability to drive and use machines
No effects on ability to drive and use machines have been observed.
4.8 Undesirable effects
There are no robust data on the frequency of undesirable effects from clinical trials. The following undesirable effects have been reported with intramuscular immunoglobulins: chest pain, dyspnoea, tremor, dizziness, facial oedema, glossitis, buccal ulceration and arthralgia. Anaphylactic reactions occur rarely and are more likely in patients who have antibodies to IgA, or who have had an allergic reaction after blood transfusion or treatment with plasma derivatives.As with all intramuscular injections, some short term discomfort can be expected at the injection site and in rare instances local induration, which can be minimised by deep intramuscular injectionFor risk of transmission of virus infections, see Section 4.4.
Consequences of an overdose are not known.
5. Pharmacological properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immune sera and immunoglobulins: Hepatitis B Immunoglobulin ATC code: J06B B04.Human Hepatitis B Immunoglobulin contains mainly immunoglobulin G (IgG) with a high content of antibodies against hepatitis B virus surface antigen (HBs).
5.2 Pharmacokinetic properties
Human Hepatitis B Immunoglobulin for intramuscular use is bioavailable in the recipient's circulation within 2-3 days. Peak serum levels occur by about 5days. 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.
5.3 Preclinical safety data
Human Hepatitis B Immunoglobulin is a preparation of human plasma proteins, so safety testing in animals is not particularly relevant to the safety of use in man. Acute toxicity studies in rat and mouse showed species specific reactions which bore no relevance to administration in humans. Repeated dose toxicity testing and embryofoetal toxicity studies are impracticable due to induction of, and interference with antibodies to human protein. Clinical experience provides no evidence of tumorigenic and mutagenic effects of immunoglobulins.
6. Pharmaceutical particulars
6.1 List of excipients
Sodium chloride, glycine, sodium acetate and a small quantity of sodium hydroxide
This medicinal product must not be mixed with other medicinal products.
6.3 Shelf life
|Stored at 2°C-8°C:||3 years.|
|Stored at 25°C:||1 week.|
6.4 Special precautions for storage
Human Hepatitis B Immunoglobulin should be stored between 2°C and 8°C. Storage for up to one week at ambient temperatures (25°C) is not detrimental. DO NOT FREEZE. Store in the original vial. Keep vial in the outer carton in order to protect from light.
6.5 Nature and contents of container
Neutral borosilicate glass vial (type I Ph.Eur.) with overseal consisting of a halobutyl rubber wad (type I Ph.Eur.), clear lacquered aluminium skirt and flip-off polypropylene cap.
6.6 Special precautions for disposal and other handling
The product should be brought to room or body temperature before use. The colour can vary from colourless to pale-yellow and is either clear or slightly opalescent. Do not use solutions that are cloudy or have deposits. Any used product or waste material should be disposed of in accordance with local requirements.The condition of date expired, or incorrectly stored product cannot be guaranteed. Such product may be unsafe, and should not be used.
7. Marketing authorisation holder
Bio Products Laboratory Limited Dagger LaneElstree HertfordshireWD6 3BXUnited Kingdom.Tel: +44 (0)20 8957 2200Fax: +44 (0)20 8957 2608Email: firstname.lastname@example.org
8. Marketing authorisation number(s)
9. Date of first authorisation/renewal of the authorisation
10. Date of revision of the text
|October 2013||Version Code: GHS12|
Bio Products Laboratory Limited
Dagger Lane, Elstree, Hertfordshire, WD6 3BX
+44 (0)20 8957 2601
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