For treatment of tetanus, the recommended dose is 150 IU/kg body weight in multiple sites. This product is NOT suitable for intravenous administration.
The volume of solution that needs to be administered to give 250 IU is stated on the label.
DO NOT EXCEED THE RECOMMENDED DOSE.
For prevention of tetanus following injury, the recommended dose is 250 iu. If more than 24 hours have elapsed between injury and treatment, or there is a risk of heavy contamination or following burns, the recommended dose is 500 iu. Children and adults must receive the same dose.
For treatment of tetanus, the recommended dose is 150 iu/kg body weight in multiple sites.
4.2.2 Method of administration
Human Tetanus Immunoglobulin should be administered via the intramuscular route .
Human Tetanus Immunoglobulin should be administered by slow injection via the intramuscular route only.
If a large volume (> 2mL 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 large total doses (³ 5 ml) are required, it is advisable to administer them in divided doses at different sites.
Human Tetanus Immunoglobulin and adsorbed vaccine should be administered with separate syringes and into different injection sites with separate lymphatic drainage.
In the case of clotting disorders where intramuscular injections are contra-indicated, Human Tetanus Immunoglobulin may be administered subcutaneously. Careful manual pressure with a compress should be applied to the site after the injection.
Human Tetanus Immunoglobulin is for single injection only; any used materials and unused solution should be discarded by approved means.
For prophylaxis, if intramuscular administration is contra-indicated (bleeding disorders), the injection can be administered subcutaneously. However, it should be noted that there are no clinical efficacy data to support administration by the subcutaneous route.
For acute therapy, if intramuscular administration is not clinically appropriate, an alternative intravenous product may be used if available.
4.3 Contra-indications
Hypersensitivity to any of the components.
Hypersensitivity to human immunoglobulins.
The lethal risk associated with tetanus rules out any potential contra-indication - see the special warnings section, below.
4.4 Special warnings and special precautions for use
Ensure that Human Tetanus Immunoglobulin is not administered into a blood vessel, because of the risk of shock
Human Tetanus Immunoglobulin must not be administered intravenously, because the preparation may cause severe reactions if given by this route.
Injections must be made intramuscularly and care should be taken to draw back the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel.
True allergic reactions to Human Tetanus Immunoglobulin are rare. when administered by the prescribed intramuscular route. In the case of shock, treatment should follow the guidelines for therapy of shock.
Human Tetanus 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 tetanus Immunoglobulin against the potential risk of hypersensitivity reactions.
Rarely, human tetanus 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. the injection be discontinued immediately. In case of shock, standard medical treatment for shock should be implemented.
Patients should be observed for at least twenty minutes after administration.
In the case of clotting disorders where intramuscular injections are normally contra-indicated, the patient should receive the appropriate medication for the disorder or the injection given subcutaneously. Careful manual pressure with a compress should be applied to the site after the injection.
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 Tetanus 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 Interactions with other medicaments and other forms of interactions
Human Tetanus Immunoglobulin may reduce the immune response to adsorbed tetanus vaccine if the two are administered at the same injection site at the same time. Human Tetanus Immunoglobulin and adsorbed tetanus vaccine should be administered with separate syringes and into different injection
Live attenuated virus vaccines
Human Tetanus Immunoglobulin administration may interfere with the development of an immune response to live attenuated virus vaccines, such as measles rubella, mumps, and varicella, for a period at least five weeks and up to of up to 3 months. After administration of this product, Such vaccinations should only be given after an interval of at least 3 months should elapse before vaccination with live attenuated virus vaccines. after administration of Human Tetanus Immunoglobulin. In the case of measles, this impairment may persist for up to 5 months.
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).
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.
There is inadequate evidence of safety in human pregnancy, but intramuscular immunoglobulins, especially Anti-D Immunoglobulin, have been widely used during pregnancy for many years without apparent ill consequence. No animal studies have been carried out. Human Tetanus Immunoglobulin should be administered to a pregnant woman or breast-feeding mother only if clearly needed. The transplacental passage of Human Tetanus Immunoglobulin may be assumed. The transfer of immunoglobulin G into the newborn during breast-feeding may be assumed.
The risk/benefit of Human Tetanus Immunoglobulin administration should be assessed for each individual case.
4.7 Effects on ability to drive and use machines
No effects on ability to drive and use machines have been observed.
There are no indications that Human Tetanus Immunoglobulin may impair the ability to drive or use machines.
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 arthralgia
glossitis buccal ulceration.
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 injection. can reduce the risk. Human Tetanus Immunoglobulin is well tolerated, although very rarely, anaphylactic reactions may occur in patients, usually with primary antibody deficiency, who have antibodies to IgA, or in patients who have had an atypical reaction to blood transfusions or treatment with plasma derivatives.
Other side effects which have been reported with intramuscular immunoglobulin are chest pain, dyspnoea, tremor, dizziness, facial oedema, glossitis, buccal ulceration and arthralgia.
For risk of transmission of virus infections, see Section 4.4.
To reduce the risk of transmission of infective agents, stringent controls are applied to the selection of blood donors and donations. In addition, virus removal and/or inactivation procedures are included in the production process.
All donations have been tested by validated procedures, and found to be non-reactive for recognised markers of virus infection (hepatitis B surface antigen, antibodies to HIV-1, HIV-2 and HCV). Plasma pools are also tested negative for these markers and additionally for HCV-RNA. The organic solvent (Tri-n-butyl Phosphate, TnBP) and detergent (Polysorbate 80) treatment in BPL’s Human Tetanus Immunoglobulin manufacturing process is used for the inactivation of lipid enveloped viruses such as hepatitis B, hepatitis C and HIV. Viral inactivation combined with donor and product screening for hepatitis and human immunodeficiency viruses greatly reduces the likelihood of viral contamination of this product. In virus inactivation studies using a model lipid enveloped virus, the solvent detergent treatment stage of BPL’s Human Tetanus Immunoglobulin manufacturing process reduces virus infectivity to undetectable levels, i.e. a minimum 6 log reduction. When medicinal products prepared from human blood or plasma are administered, the transmission of disease by infective agents of known, and as of yet unknown origin, cannot be totally excluded.
The current procedures applied in the manufacture of medicinal products derived from human blood or plasma are effective against enveloped viruses such as HIV, hepatitis B and hepatitis C viruses, but are of limited value against non-enveloped viruses such as hepatitis A virus.
4.9 Overdose
Consequences of an overdose are not known.
Human Tetanus Immunoglobulin is a concentrate of the gammaglobulin fraction of human immune plasma. Overdosage is unlikely to lead to more frequent or more severe adverse reactions than the recommended dose.
5. Pharmacological Properties
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: immune sera and immunoglobulins: Human Tetanus Immunoglobulin. ATC code: J06B B02.
Human tetanus Immunoglobulin contains mainly immunoglobulin G (IgG) with a specifically high content of antibodies against the toxin produced by the bacteria clostridium tetanus.
Human Tetanus Immunoglobulin contains specific neutralising antibodies (mainly IgG) which recognise and bind to the invading antigen (i.e. tetanus toxin). The complex is removed by the body by either complement activation or phagocytosis. It is prepared from pooled donors’ plasma containing specific antibodies against toxin of Clostridium tetani.
Currently 0.01 iu of tetanus antitoxin per ml of serum is considered to be the minimum level at which tetanus will not occur in the event that tetanus toxin is produced in the human body, as a result of infection.
5.2 Pharmacokinetic properties
Human tetanus immunoglobulin for intramuscular use is bioavailable in the recipient’s circulation after a delay of 2-3 days.
Human tetanus 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.
Measurable levels of antibodies to tetanus are found in serum approximately twenty minutes after intramuscular injection. Peak serum levels are achieved two to three days later.
The biological half-life is 21-22 days, i.e. that time taken for a 50% reduction of peak concentration in the plasma.
6. Pharmaceutical Particulars
6.1 List of excipients
Sodium chloride, Glycine and Sodium acetate
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products.
Pharmaceutical agents should not normally be added to Human Tetanus Immunoglobulin as their effects on the product have not been established.
6.4 Special precautions for storage
Human Tetanus Immunoglobulin should be stored in the original container at 2°C to 8°C. Storage for up to one week at ambient temperatures (25°C) in the original container is not detrimental. DO NOT FREEZE.
Store in the original vial. Keep vial in the outer carton in order to protect from light.
6.6 Instruction for use and handling and disposal
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.
Human Tetanus Immunoglobulin is for single use only; any used materials and unused solution should be discarded by approved means.
The condition of date expired, or incorrectly stored product cannot be guaranteed. Such product may be unsafe, and should not be used.
Solutions which are cloudy or have deposits should not be used.
7. Marketing Authorisation Holder
Bio Products Laboratory
Dagger Lane
Elstree
Hertfordshire
WD6 3BX
United Kingdom.
Tel: +44 (0)20 8258 2200
Fax: +44 (0)20 8258 2608
Email: info@bpl.co.uk
10. Date of (Partial) Revision of the Text
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November 2008
February 2003
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Version Code: GTS10
GTS9
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POM
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