Drugs List

Therapeutic Indications

Uses

Immediate prophylaxis in persons with recent injuries who have no immunity, incomplete or unknown immunity against tetanus including patients with severe deficiency in antibody production and vaccinated patients with high risk wounds.

Therapy of clinically manifest tetanus in conjunction with tetanus vaccination unless vaccination contraindicated or vaccinated status confirmed.

For comprehensive information or advice on this product, the following website should be accessed.

https://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/index.htm

Administration

For intramuscular injection only.

In patients with bleeding disorders where intramuscular administration is contraindicated, prophylactic doses may be given subcutaneously although there is no clinical efficacy to support subcutaneous administration.

If more than 5ml is required (adults) or 2ml (children), the total dose should be divided and administered at different sites.

If given simultaneously with tetanus vaccine, different sites should be used for the immunoglobulin and the vaccine.

Contraindications

None known.

Precautions and Warnings

For intramuscular administration only.

Although true allergic reaction are rare, the product contains small amounts if IgA. Patients with IgA deficiency have the potential to develop IgA antibodies and suffer anaphylactic reactions after administration of products containing IgA.

Anaphylactic reaction may occur even in patients who have previously received treatment with human immunoglobulin.

Treatment should follow the guidelines of shock therapy including immediate discontinuation of the injection.

When medicinal products prepared from human blood or plasma are administered, infectious disease due to the transmission of infective agents cannot be totally excluded.

Standard measures to prevent transmission of viruses include selection of donors, screening of individual donations and plasma pools for specific markers of infection and inclusion of effective manufacturing steps for inactivation/removal of viruses.
The manufacturer states that these measures are effective for enveloped viruses including HIV, hepatitis C and hepatitis B. They may be of limited value against non-enveloped viruses such as hepatitis A and parvovirus B19.

The name and batch number of product should be recorded on the patient's medical record.

Administration of human immunoglobulin may interfere with the development of antibodies to live, attenuated vaccines such a measles, mumps or rubella. A period of at least 3 months should elapse before vaccination with live vaccines - 5 months for measles vaccine.

Pregnancy and Lactation

Pregnancy

The safety of this product for use during human pregnancy has not been established in controlled clinical trials.

Clinical experience with immunoglobulins suggests that no harmful effects on the course of the pregnancy, or to the foetus or neonate are to be expected.

Human immunoglobulins cross the placenta. The amounts that cross to the foetus vary in the course of the pregnancy, possibly as a function of gestational age, duration of treatment and/or the method of preparation of the immunoglobulins.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It should be noted that immunoglobulins are a natural constituent of breast milk and that treatment may in fact contribute to the transfer of protective antibodies to the neonate. Moreover, it is not known whether therapy with immunoglobulins results in any significant excess levels in milk, even when large intravenous doses are administered to the mother. The contributors to the reference drug and lactation database, LactMed, recently reviewed studies investigating nursing infants whose mothers were treated with intravenous normal immunoglobulins. The authors observe that no serious adverse effects had been reported in the infants, apart from a transient rash that occurred one day after the dose was administered to the mother. No specific reports for the use of tetanus immunoglobulin have been located.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Injection site reactions

Anaphylactic reactions (more likely in patients with antibodies to IgA or who have had a previous allergic reaction after treatment with blood products)

Adverse effects reported with other intramuscular immunoglobulins include:
Chest pain
Dyspnoea
Tremor
Dizziness
Facial oedema
Arthralgia
Glossitis
Buccal ulceration

Presentation

Solution for injection containing not less than 100 i.u./ml of specific IgG to tetanus toxin in nominal 250 i.u. vials.

The corrected volume to give the stated potency is overprinted on the label.

The solution contains 40 to 180g/litre of human protein of which at least 95% is IgG.

Drugs List

Therapeutic Indications

Uses

Immediate prophylaxis in persons with recent injuries who have no immunity, incomplete or unknown immunity against tetanus including patients with severe deficiency in antibody production and vaccinated patients with high risk wounds.

Therapy of clinically manifest tetanus in conjunction with tetanus vaccination unless vaccination contraindicated or vaccinated status confirmed.

For comprehensive information or advice on this product, the following website should be accessed.

https://www.dh.gov.uk/en/Publichealth/Healthprotection/Immunisation/Greenbook/index.htm

Dosage

Tetanus Prophylaxis

A single dose of 250 i.u. given intramuscularly gives passive immunisation against tetanus. See Additional dosage for examples of tetanus-prone injuries.

If there is a risk of heavy contamination with Clostridium tetani, the wound is older than 24 hours, or following burns, then 500 i.u. should be given.

To reduce the risk of infection, thorough cleansing of the wound is essential.

Tetanus vaccine given simultaneously may not boost protection early enough to give additional protection within the incubation period of tetanus, but ensures that the patient is protected against future exposure.
Tetanus immunoglobulin does not impair the development of active immunity if given at the same time as adsorbed tetanus vaccine.

Tetanus Treatment

Doses of tetanus immunoglobulin 150 i.u. per kg of bodyweight intramuscularly divided across several sites.

An alternative product suitable for intravenous infusion is available on a named-patient basis from the Bio Products Laboratory in England and Wales, the Scottish National Blood Transfusion Service in Scotland and the Northern Ireland Blood Transfusion Services in Northern Ireland.

If advised by the Health Protection Agency: Tetanus prophylaxis (intramuscular injection) :

If tetanus immunoglobulin cannot be sourced, human normal immunoglobulin for subcutaneous use (Subgam) may be given intramuscularly as an alternative. The volume of Subgam required to achieve the recommended dose of 250iu is approximately 5ml.

Further information available from the Centre for Infections and other regional Health Protection Agency offices.

Additional Dosage Information

Administration

For intramuscular injection only.

In patients with bleeding disorders where intramuscular administration is contraindicated, prophylactic doses may be given subcutaneously although there is no clinical efficacy to support subcutaneous administration.

If more than 5ml is required (adults) or 2ml (children), the total dose should be divided and administered at different sites.

If given simultaneously with tetanus vaccine, different sites should be used for the immunoglobulin and the vaccine.

Contraindications

None known.

Precautions and Warnings

For intramuscular administration only.

Although true allergic reaction are rare, the product contains small amounts if IgA. Patients with IgA deficiency have the potential to develop IgA antibodies and suffer anaphylactic reactions after administration of products containing IgA.

Anaphylactic reaction may occur even in patients who have previously received treatment with human immunoglobulin.

Treatment should follow the guidelines of shock therapy including immediate discontinuation of the injection.

When medicinal products prepared from human blood or plasma are administered, infectious disease due to the transmission of infective agents cannot be totally excluded.

Standard measures to prevent transmission of viruses include selection of donors, screening of individual donations and plasma pools for specific markers of infection and inclusion of effective manufacturing steps for inactivation/removal of viruses.
The manufacturer states that these measures are effective for enveloped viruses including HIV, hepatitis C and hepatitis B. They may be of limited value against non-enveloped viruses such as hepatitis A and parvovirus B19.

The name and batch number of product should be recorded on the patient's medical record.

Administration of human immunoglobulin may interfere with the development of antibodies to live, attenuated vaccines such a measles, mumps or rubella. A period of at least 3 months should elapse before vaccination with live vaccines - 5 months for measles vaccine.

Pregnancy and Lactation

Pregnancy

The safety of this product for use during human pregnancy has not been established in controlled clinical trials.

Clinical experience with immunoglobulins suggests that no harmful effects on the course of the pregnancy, or to the foetus or neonate are to be expected.

Human immunoglobulins cross the placenta. The amounts that cross to the foetus vary in the course of the pregnancy, possibly as a function of gestational age, duration of treatment and/or the method of preparation of the immunoglobulins.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

It should be noted that immunoglobulins are a natural constituent of breast milk and that treatment may in fact contribute to the transfer of protective antibodies to the neonate. Moreover, it is not known whether therapy with immunoglobulins results in any significant excess levels in milk, even when large intravenous doses are administered to the mother. The contributors to the reference drug and lactation database, LactMed, recently reviewed studies investigating nursing infants whose mothers were treated with intravenous normal immunoglobulins. The authors observe that no serious adverse effects had been reported in the infants, apart from a transient rash that occurred one day after the dose was administered to the mother. No specific reports for the use of tetanus immunoglobulin have been located.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Injection site reactions

Anaphylactic reactions (more likely in patients with antibodies to IgA or who have had a previous allergic reaction after treatment with blood products)

Adverse effects reported with other intramuscular immunoglobulins include:
Chest pain
Dyspnoea
Tremor
Dizziness
Facial oedema
Arthralgia
Glossitis
Buccal ulceration

Effects on Laboratory Tests

After administration 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 (reticulocyte count, haptoglobin and Coombs test).

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store between 2 degrees C and 8 degrees C.

Do not freeze.

Protect from light.

Reference Sources

British National Formulary, 62nd Edition (2011) Pharmaceutical Press, London.

BNF for Children (2011-2012) Pharmaceutical Press, London.

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Immunisation against infectious disease: The Green Book. November 2006.

Summary of Product Characteristics: Human Tetanus Immunoglobulin. Bio Products Laboratory. Revised November 2008

Human normal immunoglobulin. Monograph available from LactMed on ToxNet. Revised October 2011.
https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: January 11, 2012.