Drugs List

Therapeutic Indications

Uses

Prevention of hepatitis B virus re-infection after liver transplantation for hepatitis B induced liver failure.

Immunoprophylaxis of hepatitis B in those who have not been vaccinated against hepatitis B (including persons whose vaccination certification is incomplete or missing).

Immunoprophylaxis in haemodialysed patients, until vaccination has become effective.

Immunoprophylaxis of hepatitis B in the newborn of a hepatitis B virus carrier-mother.

Immunoprophylaxis in patients who did not show an immune response after vaccination and for whom continuous prevention is necessary due to the continuous risk of being infected.

Administration

Infuse intravenously at an initial rate of 0.1 ml/kg/hr for 10 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum of 1 ml/kg/hr.

Clinical experience in newborns of a hepatitis B virus carrier mother has shown that hepatitis B immunoglobulin infused at a rate of 2 ml for 5 to 15 minutes has been well tolerated.

The first vaccine dose can be injected on the same day as human hepatitis B immunoglobulin, but should be administered at different sites.

Handling

The product should be brought to room temperature before use.

The solution should be clear or slightly opalescent.

Incompatibilities

Precautions and Warnings

Use with caution in patients with thrombotic risk factors since thromboembolic complications have been associated with the use of normal immunoglobulins.

Monitor serum anti-HBs antibody levels regularly.

Certain severe adverse reactions may be related to the rate of the infusion. The infusion rate recommended by the manufacturer must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.

Adverse reactions may occur more frequently in the following cases:
High rate of infusion
Patients with hypogammaglobulinaemia
Patients with agammaglobulinaemia

Hypersensitivity reactions can occur in the very seldom cases of IgA deficiency with anti-IgA antibodies.

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

If allergic or anaphylactic reactions occur, treatment must be discontinued immediately. Cases of shock should be managed according to the current medical standards for shock treatment. Adrenaline should be available in case of any anaphylactic reaction.

Despite all precautions taken by manufacturers, when medicinal products are derived from human blood or plasma, infectious diseases due to transmission of infective agents cannot be totally excluded.

It is advisable to record the name and batch number of the product administered.

After administration of this product, an interval of 3 months should elapse before vaccination with live virus vaccines as immunoglobulin administration may impair the efficacy of live attenuated virus vaccines.

Hepatitis B immunoglobulin should be administered three to four weeks after vaccination with live vaccines. If administration of hepatitis B immunoglobulin is essential within three to four weeks after vaccination, then revaccination should be performed three months after the administration of hepatitis B immunoglobulin.

May affect results of some laboratory tests - see Laboratory Tests .

Pregnancy - see 'Pregnancy' section

Breastfeeding - see 'Lactation' section

Pregnancy and Lactation

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.

Continued treatment of the pregnant women is important to ensure that the neonate is born with appropriate passive immunity.

The American College of Obstetricians and Gynecologists recommends use of hepatitis B immunoglobulin during pregnancy for post exposure prophylaxis (Briggs 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 14-17 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

UK licensed product information stresses that the safety of human immunoglobulins during breastfeeding 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 from 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

Drug excreted in breast milk? - Yes.

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - Yes.

Side Effects

Chills
Headache
Fever
Vomiting
Nausea
Arthralgia
Hypotension
Anaphylactic shock
Aseptic meningitis
Haemolytic anaemia
Haemolysis
Cutaneous reactions
Serum creatinine increased
Acute renal failure
Itching
Pruritus
Hypersensitivity reactions
Tachycardia
Erythema
Malaise
Thromboembolic disorders
Injection site reactions
Buccal ulceration
Glossitis
Abdominal pain
Chest pain
Dyspnoea
Anaphylaxis
Tremor
Dizziness

Presentation

Solution for infusion containing 50mg/ml human plasma protein of which at least 96% are immunoglobulin G.

1ml contains 50 IU of hepatitis B antibody.

Drugs List

Therapeutic Indications

Uses

Prevention of hepatitis B virus re-infection after liver transplantation for hepatitis B induced liver failure.

Immunoprophylaxis of hepatitis B in those who have not been vaccinated against hepatitis B (including persons whose vaccination certification is incomplete or missing).

Immunoprophylaxis in haemodialysed patients, until vaccination has become effective.

Immunoprophylaxis of hepatitis B in the newborn of a hepatitis B virus carrier-mother.

Immunoprophylaxis in patients who did not show an immune response after vaccination and for whom continuous prevention is necessary due to the continuous risk of being infected.

Dosage

Adults

Elderly

Children

Neonates

Administration

Infuse intravenously at an initial rate of 0.1 ml/kg/hr for 10 minutes. If well tolerated, the rate of administration may gradually be increased to a maximum of 1 ml/kg/hr.

Clinical experience in newborns of a hepatitis B virus carrier mother has shown that hepatitis B immunoglobulin infused at a rate of 2 ml for 5 to 15 minutes has been well tolerated.

The first vaccine dose can be injected on the same day as human hepatitis B immunoglobulin, but should be administered at different sites.

Handling

The product should be brought to room temperature before use.

The solution should be clear or slightly opalescent.

Incompatibilities

Precautions and Warnings

Use with caution in patients with thrombotic risk factors since thromboembolic complications have been associated with the use of normal immunoglobulins.

Monitor serum anti-HBs antibody levels regularly.

Certain severe adverse reactions may be related to the rate of the infusion. The infusion rate recommended by the manufacturer must be closely followed. Patients must be closely monitored and carefully observed for any symptoms throughout the infusion period.

Adverse reactions may occur more frequently in the following cases:
High rate of infusion
Patients with hypogammaglobulinaemia
Patients with agammaglobulinaemia

Hypersensitivity reactions can occur in the very seldom cases of IgA deficiency with anti-IgA antibodies.

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

If allergic or anaphylactic reactions occur, treatment must be discontinued immediately. Cases of shock should be managed according to the current medical standards for shock treatment. Adrenaline should be available in case of any anaphylactic reaction.

Despite all precautions taken by manufacturers, when medicinal products are derived from human blood or plasma, infectious diseases due to transmission of infective agents cannot be totally excluded.

It is advisable to record the name and batch number of the product administered.

After administration of this product, an interval of 3 months should elapse before vaccination with live virus vaccines as immunoglobulin administration may impair the efficacy of live attenuated virus vaccines.

Hepatitis B immunoglobulin should be administered three to four weeks after vaccination with live vaccines. If administration of hepatitis B immunoglobulin is essential within three to four weeks after vaccination, then revaccination should be performed three months after the administration of hepatitis B immunoglobulin.

May affect results of some laboratory tests - see Laboratory Tests .

Pregnancy - see 'Pregnancy' section

Breastfeeding - see 'Lactation' section

Pregnancy and Lactation

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.

Continued treatment of the pregnant women is important to ensure that the neonate is born with appropriate passive immunity.

The American College of Obstetricians and Gynecologists recommends use of hepatitis B immunoglobulin during pregnancy for post exposure prophylaxis (Briggs 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 14-17 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

UK licensed product information stresses that the safety of human immunoglobulins during breastfeeding 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 from 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

Drug excreted in breast milk? - Yes.

Considered suitable or recommended by manufacturer? - No.

Drug substance licensed in infants? - Yes.

Side Effects

Chills
Headache
Fever
Vomiting
Nausea
Arthralgia
Hypotension
Anaphylactic shock
Aseptic meningitis
Haemolytic anaemia
Haemolysis
Cutaneous reactions
Serum creatinine increased
Acute renal failure
Itching
Pruritus
Hypersensitivity reactions
Tachycardia
Erythema
Malaise
Thromboembolic disorders
Injection site reactions
Buccal ulceration
Glossitis
Abdominal pain
Chest pain
Dyspnoea
Anaphylaxis
Tremor
Dizziness

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 (e.g. 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 at 2 to 8 degrees C.

Do not freeze.

Reference Sources

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

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

Human normal immunoglobulin. Monograph available from LactMed on ToxNet. Revised October 2011.
https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Last accessed: 8 March 2012

Summary of Product Characteristics: Hepatect CP 50 IU/ml solution for infusion. Biotest UK Ltd. Revised March 2011.