HUMAN TETANUS IMMUNOGLOBULIN 100 IU/ML SOLUTION FOR INJECTION - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Human Tetanus Immunoglobulin, 100 IU/mL solution for injection.

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Human Tetanus Immunoglobulin Ph.Eur. contains human protein, 40–180 g/L of which at least 95% is IgG. The concentration of specific IgG to tetanus toxin is not less than 100 IU/ml in nominal 250 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

4.   CLINICAL PARTICULARS

4.1. Therapeutic indications

Post-exposure prophylaxis:

Immediate prophylaxis after tetanus prone injuries in patients not adequately vaccinated, in patients whose immunisation status is not known with certainty, and in patients with severe deficiency in antibody production or vaccinated patients with high risk wounds.

4.2. Posology and method of administration

4.2.1 Posology

Prophylaxis of tetanus prone wounds:

250 IU, unless the risk is thought to be extremely high

The dose may be increased to 500 IU in:

Infected wounds, where surgically appropriate treatment cannot be achieved within 24 hours

Deep or contaminated wounds with tissue damage and reduced oxygen supply, as well as foreign body injury (e.g. bites, stings or shots)

The volume of solution that needs to be administered to give 250 IU is stated on the label.

DO NOT EXCEED THE RECOMMENDED DOSE.

4.2.2 Method of administration

Human Tetanus Immunoglobulin should be administered via the intramuscular rou­te.

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 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.

4.3 Contra-indications

Hypersensitivity to any of the components.

Hypersensitivity to human immunoglobulins.

4.4 Special warnings and precautions for use

Ensure that Human Tetanus Immunoglobulin is not administered into a blood vessel, because of the risk of shock.

True allergic reactions are rare.

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. 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped hepatitis A and parvovirus B19 viruses

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

Live attenuated virus vaccines

Immunoglobulin administration may interfere with the development of an immune response to live attenuated virus vaccines, such as rubella, mumps, and varicella, for a period of up to 3 months. After administration of this product, an interval of at least 3 months should elapse before vaccination with live attenuated virus vaccines. 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.

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:

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.

For risk of transmission of virus infections, see Section 4.4.

4.9 Overdose

5.    Pharmacological Properties5.1 Pharmacodynamic properties

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.

5.3 Preclinical safety data

Human Tetanus 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 bear no relevance to administration in humans. Repeated dose toxicity testing and embryo-fetal toxicity studies are impracticable due to the induction of, and interference with antibodies to human protein. Clinical experience provides no evidence of tumourigenic and mutagenic effects of immunoglobulins.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Sodium chloride

Glycine

Sodium acetate trihydrate

Sodium hydroxide

6.2 Incompatibilities

This medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

Stored at 2°C-8°C:

2 years.

1 week.

Stored at 25°C:

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.

6.5 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

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.

7. MARKETING AUTHORISATION HOLDER

Bio Products Laboratory Limited

Dagger Lane

Elstree

Hertfordshire

WD6 3BX

United Kingdom.

8 MARKETING AUTHORISATION NUMBER(S)

PL 08801/0011