Drugs List

Therapeutic Indications

Uses

Hepatitis B -prophylaxis after exposure

Immunoprophylaxis of hepatitis B:

In case of accidental exposure 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 is less than or equal to 1,500g irrespective of e-antigen status of mother).
In subjects who did not show an immune response 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.
In HBV-DNA negative patients at least 1 week after liver transplantation for hepatitis B induced liver failure.

Not all brands are licensed for all indications.

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

https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book

Administration

Zutectra is for subcutaneous administration

Human hepatitis B immunoglobulin (BPL) is for intramuscular administration. However, in patients with bleeding disorders, the injection may be administered subcutaneously if no intravenous product is available. There is no clinical efficacy data to support administration by the subcutaneous route.

When administered intramuscularly, the recommended site for adults is the deltoid, and for infants the lateral aspect of the thigh is preferable. If a large volume (greater than 2 ml for children or greater than 5 ml for adults) is required, it is recommended to administer this in divided doses at different sites.

If hepatitis B vaccine is given the same day as human hepatitis B immunoglobulin, different administration sites should be used.

Not all brands are licensed for all routes of administration.

Contraindications

None known

Precautions and Warnings

Immunoglobulin A antibodies
Breastfeeding
Immunoglobulin A deficiency
Pregnancy

Live virus vaccine should not be given for 3 months after treatment
Inject product slowly at start of treatment to test sensitivity
Not all available brands are licensed for all age groups
Not all available brands are licensed for all routes of administration
Derived from human plasma. Transmission of infective agents possible.
Have adrenaline injection ready for use in case of anaphylaxis
May be administered simultaneously with HB vaccine - at different site
Record name and batch number of administered product
Warm to room temperature prior to use
Monitor patient for at least 20 minutes post injection
Management of cases of shock should follow current medical standards
May affect results of some laboratory tests
May interfere with antibody tests
Discontinue if allergic reaction occurs

If the recipient is a carrier of HBsAg, there is no benefit in administering the product.

Allergic reactions to human hepatitis B immunoglobulin are rare. Human hepatitis B immunoglobulin contains a small quantity of IgA. Individuals 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 weigh up the benefit of treatment against the potential risk of hypersensitivity reactions.

Human hepatitis B immunoglobulin may cause a sudden fall in blood pressure with anaphylactoid reactions, even in patients who have tolerated previous immunoglobulin treatment.

Human hepatitis B immunoglobulin should be administered three to four weeks after vaccination with a live attenuated vaccine. In case human hepatitis B immunoglobulin is required within three to four weeks after vaccination, then revaccination should be performed three months after the administration of human hepatitis B immunoglobulin.

Pregnancy and Lactation

Pregnancy

Use immunoglobulin human hepatitis B with caution in pregnancy.

The safety of this product for use during human pregnancy has not been established in controlled clinical trials. Therefore, human immunoglobulins should only be given with caution in pregnant women. 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.

The American College of Obstetricians and Gynaecologists recommends use of Hepatitis B immune globulin in pregnancy for post-exposure prophylaxis. Hepatitis B immune globulin is used to provide passive immunity following exposure to hepatitis B (Briggs et al, 2011).

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 to 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

Use immunoglobulin human hepatitis B with caution in breastfeeding.

UK licensed product information stresses that the safety of human immunoglobulins in lactation has not been established in controlled clinical trials. It therefore concludes that human immunoglobulins should only be given with caution to breastfeeding mothers.

However, it should be noted that immunoglobulins are a natural constituent of breast milk. 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 immunoglobulins. The authors observe that no serious adverse effects had been reported in the infants, apart for a transient rash that occurred one day after the dose was administered to the mother.

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

Abdominal pain
Arthralgia
Buccal ulceration
Cardiac symptoms
Chest pain
Dizziness
Dyspnoea
Erythema at injection site
Facial oedema
Fatigue
Glossitis
Haematoma (injection site)
Headache
Hypersensitivity reactions including anaphylaxis
Hypertension
Induration (injection site)
Local pain (injection site)
Muscle spasm
Nasopharyngitis
Oropharyngeal pain
Palpitations
Pruritus
Rash
Tiredness
Tremor
Urticaria

Presentation

Injection containing human hepatitis B immunoglobulin

Drugs List

Therapeutic Indications

Uses

Hepatitis B -prophylaxis after exposure

Immunoprophylaxis of hepatitis B:

In case of accidental exposure 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 is less than or equal to 1,500g irrespective of e-antigen status of mother).
In subjects who did not show an immune response 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.
In HBV-DNA negative patients at least 1 week after liver transplantation for hepatitis B induced liver failure.

Not all brands are licensed for all indications.

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

https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book

Dosage

Not all brands are licensed for all age groups.

Adults

Elderly

Children

Neonates

Additional Dosage Information

Administration

Zutectra is for subcutaneous administration

Human hepatitis B immunoglobulin (BPL) is for intramuscular administration. However, in patients with bleeding disorders, the injection may be administered subcutaneously if no intravenous product is available. There is no clinical efficacy data to support administration by the subcutaneous route.

When administered intramuscularly, the recommended site for adults is the deltoid, and for infants the lateral aspect of the thigh is preferable. If a large volume (greater than 2 ml for children or greater than 5 ml for adults) is required, it is recommended to administer this in divided doses at different sites.

If hepatitis B vaccine is given the same day as human hepatitis B immunoglobulin, different administration sites should be used.

Not all brands are licensed for all routes of administration.

Contraindications

None known

Precautions and Warnings

Immunoglobulin A antibodies
Breastfeeding
Immunoglobulin A deficiency
Pregnancy

Live virus vaccine should not be given for 3 months after treatment
Inject product slowly at start of treatment to test sensitivity
Not all available brands are licensed for all age groups
Not all available brands are licensed for all routes of administration
Derived from human plasma. Transmission of infective agents possible.
Have adrenaline injection ready for use in case of anaphylaxis
May be administered simultaneously with HB vaccine - at different site
Record name and batch number of administered product
Warm to room temperature prior to use
Monitor patient for at least 20 minutes post injection
Management of cases of shock should follow current medical standards
May affect results of some laboratory tests
May interfere with antibody tests
Discontinue if allergic reaction occurs

If the recipient is a carrier of HBsAg, there is no benefit in administering the product.

Allergic reactions to human hepatitis B immunoglobulin are rare. Human hepatitis B immunoglobulin contains a small quantity of IgA. Individuals 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 weigh up the benefit of treatment against the potential risk of hypersensitivity reactions.

Human hepatitis B immunoglobulin may cause a sudden fall in blood pressure with anaphylactoid reactions, even in patients who have tolerated previous immunoglobulin treatment.

Human hepatitis B immunoglobulin should be administered three to four weeks after vaccination with a live attenuated vaccine. In case human hepatitis B immunoglobulin is required within three to four weeks after vaccination, then revaccination should be performed three months after the administration of human hepatitis B immunoglobulin.

Pregnancy and Lactation

Pregnancy

Use immunoglobulin human hepatitis B with caution in pregnancy.

The safety of this product for use during human pregnancy has not been established in controlled clinical trials. Therefore, human immunoglobulins should only be given with caution in pregnant women. 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.

The American College of Obstetricians and Gynaecologists recommends use of Hepatitis B immune globulin in pregnancy for post-exposure prophylaxis. Hepatitis B immune globulin is used to provide passive immunity following exposure to hepatitis B (Briggs et al, 2011).

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 to 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

Use immunoglobulin human hepatitis B with caution in breastfeeding.

UK licensed product information stresses that the safety of human immunoglobulins in lactation has not been established in controlled clinical trials. It therefore concludes that human immunoglobulins should only be given with caution to breastfeeding mothers.

However, it should be noted that immunoglobulins are a natural constituent of breast milk. 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 immunoglobulins. The authors observe that no serious adverse effects had been reported in the infants, apart for a transient rash that occurred one day after the dose was administered to the mother.

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

Abdominal pain
Arthralgia
Buccal ulceration
Cardiac symptoms
Chest pain
Dizziness
Dyspnoea
Erythema at injection site
Facial oedema
Fatigue
Glossitis
Haematoma (injection site)
Headache
Hypersensitivity reactions including anaphylaxis
Hypertension
Induration (injection site)
Local pain (injection site)
Muscle spasm
Nasopharyngitis
Oropharyngeal pain
Palpitations
Pruritus
Rash
Tiredness
Tremor
Urticaria

Effects on Laboratory Tests

The transitory rise of passively transferred antibodies in the patients blood may result in misleading positive results in serological testing. Passive transmission of antibodies to erythrocyte antigens may interfere with some serological tests for red cell antibodies, for example the antiglobulin test (Coomb's 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 ).

Further Information

Last Full Review Date: January 2016

Reference Sources

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.

Joint Formulary Committee. British National Formulary. 70th ed. London: BMJ Group and Pharmaceutical Press; 2015.

Paediatric Formulary Committee. BNF for Children 2014-2015. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2014.

Summary of Product Characteristics: Human Hepatitis B Immunoglobulin, 100 IU/ml sterile solution. Bio Products Laboratory Limited. Revised October 2013.

Summary of Product Characteristics: Zutectra 500 IU solution for injection in pre-filled syringe. Biotest (UK) Ltd. Revised December 2015.

Human normal immunoglobulin. Monograph available from LactMed on ToxNet. Revised September 2015.
https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: 13 January 2016