1. Name Of The Medicinal Product
Tetabulin®
Tetanus Immunoglobulin B.P. Immuno
2. Qualitative And Quantitative Composition
Active Ingredient: Tetanus antitoxin
Quantitative Composition
1ml of solution contains Tetanus antitoxin 250 IU
3. Pharmaceutical Form
Solution for intramuscular administration.
4. Clinical Particulars
4.1 Therapeutic Indications
Prophylaxis in persons with recent injuries who have no immunity, incomplete or unknown immunity against tetanus
Therapy of clinically manifest tetanus
4.2 Posology And Method Of Administration
(a) Tetanus Prophylaxis
Passive immunisation against tetanus is recommended in all cases of injury where a risk of tetanus infection is involved and where active protection against tetanus is insufficient, i.e. when immunisation is incomplete, when the immune response is reduced or following severe loss of blood or plasma.
Tetabulin is also indicated when the status of immunisation is unknown or when active immunisation is contraindicated.
To reduce the risk of tetanus infection thorough debridement and cleansing of the wound is recommended along with the injection of Tetabulin and if necessary, administration of antibiotics.
Passive immunisation against tetanus is achieved by intramuscular administration of a single dose of Tetabulin (250 IU tetanus immunoglobulin).
If there is a risk of heavy contamination of the wound with tetanus bacilli or if the wounds are older than 12 hours or in patients weighing more than 90kg, an additional dose of Tetabulin (250 IU tetanus immunoglobulin) should be given.
Patients with antibody deficiency syndrome such as dys-, hypo- or agammaglobulinaemia or with a reduced capacity of antibody formation (after radiotherapy or steroid treatment, burns, etc) should receive another dose of Tetabulin (250 IU tetanus immunoglobulin) 3 to 4 weeks after the first dose as prophylaxis against delayed onset of tetanus.
Passive immunisation against tetanus should be complemented by active immunisation with tetanus vaccine (simultaneous prophylaxis or simultaneous vaccination) except in the case of a given contraindication against the use of tetanus vaccine.
Where simultaneous vaccination is contraindicated a further 250 IU of tetanus immunoglobulin (Tetabulin) should be given 3 to 4 weeks after the first Tetabulin injection as prophylaxis against delayed tetanus.
Simultaneous vaccination is indicated in cases of:
a) Absent, inadequate or insufficiently documented active immunisation; especially in unconscious patients.
b) Risk of antibody deficiency syndrome or reduced capacity of antibody formation.
c) Risk of heavy contamination of the wound with tetanus bacilli.
d) Injuries older than 12 hours.
e) Severe burns.
Simultaneous vaccination is carried out in the following way:
1 dose of Tetabulin (250 IU tetanus immunoglobulin) is given intramuscularly and at the same time but at another site (e.g. in the upper arm) a dose of tetanus vaccine is given using a different syringe. If there is a risk of heavy contamination of the wound by tetanus bacilli, 2 x 250 IU (500 IU) of Tetabulin should be given.
In cases of antibody deficiency syndrome or reduced capacity of antibody formation the procedure described under passive immunisation should be followed. Tetanus immunoglobulin does not impair the development of active immunity if given at the same time as adsorbed tetanus vaccine.
If simultaneous tetanus vaccination has been carried out, it is important to administer another dose of tetanus vaccine after 3 to 6 weeks in order to avoid delayed manifestation of tetanus as a consequence of endogenous tetanus antitoxin production. Active immunisation must be completed after about one year with a third dose of tetanus vaccine.
Immunisation lasts at least 5 years. Thereafter a booster dose of tetanus vaccine should be administered subcutaneously or intramuscularly every 5 to 10 years.
(b) Tetanus Treatment
Doses of tetanus immunoglobulin between 30 and 300 IU per kg bodyweight have been given.
The absence of thiomersal as a preservative theoretically allows intrathecal administration, although efficacy and safety in children and adults have not yet been definitely assessed.
No special precautions need to be observed in the elderly.
Method of Administration
Slow injection by the i.m. route only.
If large doses (
4.3 Contraindications
The lethal risk associated with tetanus rules out any potential contraindication (see Warnings below).
4.4 Special Warnings And Precautions For Use
The warnings and precautions described for human normal immunoglobulin (i.m) may be applied for Tetanus Immunoglobulin BP Immuno and are described below.
Do not give this product intravascularly (possibility of shock). Therefore, it is necessary to verify that the needle has not penetrated a blood vessel.
Give with caution in highly allergic individuals due to the potential risk of hypersensitivity reactions such as anaphylactoid shock.
Measures against allergic and anaphylactoid reactions require immediate discontinuation of the injection. If allergic reactions persist after discontinuation of the injection, then appropriate treatment with, for example, antihistamines and/or corticosteroids is recommended.
In anaphylactoid shock, treatment should follow the guidelines of shock therapy.
When medicinal products prepared from human blood or plasma are administered, infectious disease due to the transmission of infective agents cannot be totally excluded. This applies also to pathogens of hitherto unknown origin. Therefore donors are selected according to strict criteria, plasma donations are screened and selected and plasma pools are tested (IMMUNO Plasma Safety Program). The manufacturing process includes measures for the removal and inactivation of viruses.
Only plasma from healthy donors which has been tested with negative results for antibodies to human immunodeficiency virus (HIV) types 1 and 2 (HIV-1 and -2) and hepatitis C virus (HCV) as well as hepatitis B virus surface antigen (HBsAg) is used for the manufacture of Tetabulin. The liver enzyme value (ALT) must not exceed the accepted threshold value (two times the upper limit of normal). Non-Returning Donor-Applicants are excluded from further donations, and each plasma donation is subjected to Inventory Hold and the Lookback Program.
A sample of the plasma pool is also tested for HIV and HCV antibodies as well as for HBsAg. In addition a test for virus genome sequences of HIV-1, HBV and HCV with the polymerase chain reaction (HIQ-PCR1) is carried out. The polymerase chain reaction (PCR) is a highly sensitive method with which, in contrast to antibody testing, direct identification of virus genomes is possible. Only plasma pools in which no genomes of these viruses are detectable are released for further processing.
Clinical studies and pharmacoepidemiological surveillance of Tetabulin have shown no product-related transmission of infectious agents.
1 HIQ-PCR (HYLAND IMMUNO Quality-Assured Polymerase Chain Reaction) is a quality-assured assay system for the detection of genomic sequences of HIV-1, HBV and HCV. With the highest degree of probability this assay system allows for the detection of 500 genome equivalents of each of the above viruses per ml, its sensitivity being below this limit. Also test results ranging below 500 genome equivalents per ml are considered positive leading to exclusion of the respective donation from further processing.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Live Attenuated Virus Vaccines
If the patient has received live attenuated virus vaccines (measles, rubella, mumps, varicella) within the two previous weeks, control of protective post-vaccinal antibodies may be of value before giving a possible booster.
After injection of immunoglobulin, wait 3 months prior to administering any live attenuated virus vaccines (measles, rubella, mumps).
The efficacy of the virus vaccines may be impaired by the antibodies contained in the immunoglobulin preparation.
4.6 Pregnancy And Lactation
The safety of this medicinal product for use in pregnancy has not been established in controlled clinical trials. Long lasting clinical experience with immunoglobulin, in particular the routine administration of anti-D immunoglobulin, does indicate that no harmful effects on the course of pregnancy, on the foetus and the neonate are to be expected (category A).
Experimental animal studies are inappropriate with respect to the product which is heterologous for animals (immunological incompatibility).
Immunoglobulins are excreted into the milk and may contribute to the transfer of protective antibodies to the neonate.
4.7 Effects On Ability To Drive And Use Machines
There are no known restrictions.
4.8 Undesirable Effects
The undesirable effects described for human normal immunoglobulin (i.m) may be applied for Tetanus Immunoglobulin BP Immuno and are described below.
Occasionally, fever, cutaneous reactions, chills may occur. In rare instances nausea, vomiting, hypotension, tachycardia, allergic reactions have been reported. Serious effects such as anaphylactoid shock have been observed in isolated cases.
4.9 Overdose
Overdosage with Tetanus Immunoglobulin BP Immuno is not known.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
The main effect of tetanus immunoglobulin, which is well established, is the neutralisation of the tetanus toxin by antitoxic antibodies.
5.2 Pharmacokinetic Properties
Following the injection of an intramuscular immunoglobulin a measurable increase in the IG-serum level is not achieved immediately but is delayed to some extent. The value first rises to a maximum and subsequently decreases according to the half-life of the preparation.
Considerable differences have been observed as to the time when a maximum plasma concentration is reached. They range from 24 hours to 2 weeks. Generally, however, values of between 3 and 7 days are found.
According to Du Pan et al 50-70% of the immunoglobulin are present at the injection site 24 hours following administration, 35% after 2 days. It seems that not all of the injection material appears in the blood circulation but that part of it is eliminated by local degradation or other mechanisms.
Measurements have shown that at the time when the serum IG-level is at its maximum only 20-40% of the total dose are detectable.
Only when very small amounts, i.e. below 5ml, are administered, resorption is possible without loss. Apart from the amount injected the extent and speed of IG-resorption depend also on the general state of health of the patient, on the activity of his muscles and on the application site.
Based on numerous investigations the half-life of the native immunoglobulin in the serum ranges between 21-27 days.
5.3 Preclinical Safety Data
Viral Safety
The respective national guidelines on the collection of human plasma in their effective version are observed. In addition, several steps of the manufacturing process contribute to the viral safety of human immunoglobulins. They result in extensive partitioning and/or inactivation of potentially contaminating viruses.
Toxicological Properties
Immunoglobulins are normal constituents of the human body. Repeated dose toxicity testing in animals is impracticable due to interference with developing antibodies.
Tetanus Immunoglobulin BP Immuno has not been reported to be associated with embryo-foetal toxicity, oncogenic or mutagenic potential.
6. Pharmaceutical Particulars
6.1 List Of Excipients
1ml of solution contains:
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6.2 Incompatibilities
Tetanus Immunoglobulin BP Immuno must not be mixed with other pharmaceutical products.
6.3 Shelf Life
3 years when stored between +2°C and +8°C.
Once a container has been opened, its contents should be used immediately.
6.4 Special Precautions For Storage
Store at a temperature of between +2°C and +8°C.
Protect from light.
Do not use after the expiry date indicated on the label.
6.5 Nature And Contents Of Container
Preloaded syringe of neutral glass, hydrolytic type I, each containing 1ml of solution.
6.6 Special Precautions For Disposal And Other Handling
Tetanus Immunoglobulin BP Immuno should be administered immediately following removal of the protective needle cover from the preloaded syringe.
Tetanus Immunoglobulin BP Immuno and syringes are intended for single dose use only.
Do not use solutions which are cloudy or have deposits.
7. Marketing Authorisation Holder
IMMUNO Ltd.,
Caxton Way,
Thetford,
Norfolk,
IP24 3SE,
United Kingdom.
8. Marketing Authorisation Number(S)
0215/0030
9. Date Of First Authorisation/Renewal Of The Authorisation
21st December 1998
10. Date Of Revision Of The Text
October 2000
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