Drugs List

Therapeutic Indications

Uses

Hypogammaglobulinaemia pre/post stem cell transplant: Replacement therapy
Primary immunodeficiency syndromes with impaired antibody production
Secondary hypogammaglobulinaemia in CLL or Myeloma with recurrent infection

Replacement therapy in primary immunodeficiency syndromes such as:
Primary immunodeficiency syndrome with impaired antibody production.
Replacement therapy in myeloma or chronic lymphatic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.
Treatment of hypogammaglobulinaemia in patients pre and post-allogeneic haematopoietic stem cell transplantation.

Administration

For subcutaneous infusion only.

Infusion rates may vary between brands (consult specific product literature).

It may be suitable or it may be required to use more than one pump simultaneously, more than one injection site can be used.

Contraindications

Severe Immunoglobulin A deficiency

Precautions and Warnings

Antibodies to immunoglobulin A
Predisposition to thromboembolic disease
Prolonged immobilisation
Restricted sodium intake
Breastfeeding
Diabetes mellitus
History of thrombosis
Hyperprolinaemia
Hypertension
Immunoglobulin A deficiency
Pregnancy
Severe hypovolaemia

Live virus vaccine should not be given for 3 months after treatment
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Inject product slowly at start of treatment to test sensitivity
Treatment to be initiated and supervised by a specialist
May contain polysorbate
Some formulations contain proline
Derived from human proteins - transmission of infective agents possible
Different brands of this product are not interchangeable
Do not dilute
Do not use if any signs of precipitate or particulate matter apparent
Monitor throughout infusion and for 1 hour post first infusion
Record name and batch number of administered product
The rate of infusion is dose dependant follow administration instructions
Vary infusion site
Ensure adequate hydration prior to infusion
Monitor for hypersensitivity reactions during infusion
Monitor IgG trough levels to adjust dose and/or dose interval
Monitor patient for at least 20 minutes post injection
Advise patient to contact a doctor if symptoms of thromboembolism develop
Increased frequency of ADRs if first human normal immunoglobulin given
Increased frequency of ADRs when treatment is stopped for more than 8 weeks
Increased frequency of adverse reactions if product is switched
Management of cases of shock should follow current medical standards
May affect immune response to live vaccines
May induce hypotension with anaphylaxis, even if prior treatment tolerated
May affect results of some laboratory tests
Discontinue if anaphylactoid reaction occurs
Discontinue if Aseptic Meningitis Syndrome occurs
Measles vaccine may not be effective for up to 1 year after treatment
Advise patient on the symptoms of Aseptic Meningitis Syndrome

Use with caution in patients deficient in IgA. These patients may produce anti-IgA antibodies, which could lead to anaphylactic reactions.

Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency, and in the guidance of patients for home treatment if applicable. The patient will be instructed in the use of a syringe driver, infusion techniques, the keeping of a treatment diary, and measures to be taken in case of severe adverse events. Once the patient is familiar with the method and no unacceptable side effects have been observed during the training phase, the treatment may be continued at home by the patient or carer.

Intravenous administration is contraindicated and if accidental administration into a blood vessel occurs the patient could develop shock.

Pregnancy and Lactation

Pregnancy

Use normal human immunoglobulin with caution in pregnancy.

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

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 (Briggs 2015, Schaefer 2015).

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 normal human immunoglobulin with caution in breastfeeding.

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.

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.

LactMed (2018), state that no serious adverse effects have been reported in infants whose mothers were treated with immunoglobulins, 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

Side Effects

Abdominal pain
Allergic reaction
Anaphylactic shock
Anti-GAD antibody positive
Anxiety
Arthralgia
Aseptic meningitis
Back pain
Blood pressure changes
Bruising at injection site
Burning sensation
Chest tightness
Chills
Diarrhoea
Dizziness
Fatigue
Fever
Flushing
Haemolytic anaemia
Headache
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Influenza-like syndrome
Infusion related reaction
Itching (injection site)
Local pain (injection site)
Migraine
Mouth ulcers
Muscle spasm
Muscle weakness
Musculoskeletal pain
Myalgia
Nausea
Oedema (injection site)
Pain
Paraesthesia
Positive Coombs test
Pruritus
Pyrexia
Rash at injection site
Sensation of cold
Somnolence
Stiffness
Swelling (injection site)
Tachycardia
Tremor
Urticaria
Vomiting

Presentation

Solution for injection containing human normal immunoglobulin for subcutaneous use only.

Drugs List

Therapeutic Indications

Uses

Hypogammaglobulinaemia pre/post stem cell transplant: Replacement therapy
Primary immunodeficiency syndromes with impaired antibody production
Secondary hypogammaglobulinaemia in CLL or Myeloma with recurrent infection

Replacement therapy in primary immunodeficiency syndromes such as:
Primary immunodeficiency syndrome with impaired antibody production.
Replacement therapy in myeloma or chronic lymphatic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections.
Treatment of hypogammaglobulinaemia in patients pre and post-allogeneic haematopoietic stem cell transplantation.

Dosage

Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency, and in the guidance of patients for home treatment if applicable.

The dose and dosage regimen is dependent on the indication, and may need to be individualised for each patient depending on the pharmacokinetic and clinical response.

IgG trough levels should be measured in order to adjust the dose and dosage interval.

The following dosage regimens are given as a guideline.

Adults

Children

Additional Dosage Information

Administration

For subcutaneous infusion only.

Infusion rates may vary between brands (consult specific product literature).

It may be suitable or it may be required to use more than one pump simultaneously, more than one injection site can be used.

Contraindications

Severe Immunoglobulin A deficiency

Precautions and Warnings

Antibodies to immunoglobulin A
Predisposition to thromboembolic disease
Prolonged immobilisation
Restricted sodium intake
Breastfeeding
Diabetes mellitus
History of thrombosis
Hyperprolinaemia
Hypertension
Immunoglobulin A deficiency
Pregnancy
Severe hypovolaemia

Live virus vaccine should not be given for 3 months after treatment
Sodium content of formulation may be significant
Advise ability to drive/operate machinery may be affected by side effects
Inject product slowly at start of treatment to test sensitivity
Treatment to be initiated and supervised by a specialist
May contain polysorbate
Some formulations contain proline
Derived from human proteins - transmission of infective agents possible
Different brands of this product are not interchangeable
Do not dilute
Do not use if any signs of precipitate or particulate matter apparent
Monitor throughout infusion and for 1 hour post first infusion
Record name and batch number of administered product
The rate of infusion is dose dependant follow administration instructions
Vary infusion site
Ensure adequate hydration prior to infusion
Monitor for hypersensitivity reactions during infusion
Monitor IgG trough levels to adjust dose and/or dose interval
Monitor patient for at least 20 minutes post injection
Advise patient to contact a doctor if symptoms of thromboembolism develop
Increased frequency of ADRs if first human normal immunoglobulin given
Increased frequency of ADRs when treatment is stopped for more than 8 weeks
Increased frequency of adverse reactions if product is switched
Management of cases of shock should follow current medical standards
May affect immune response to live vaccines
May induce hypotension with anaphylaxis, even if prior treatment tolerated
May affect results of some laboratory tests
Discontinue if anaphylactoid reaction occurs
Discontinue if Aseptic Meningitis Syndrome occurs
Measles vaccine may not be effective for up to 1 year after treatment
Advise patient on the symptoms of Aseptic Meningitis Syndrome

Use with caution in patients deficient in IgA. These patients may produce anti-IgA antibodies, which could lead to anaphylactic reactions.

Treatment should be initiated and monitored under the supervision of a physician experienced in the treatment of immunodeficiency, and in the guidance of patients for home treatment if applicable. The patient will be instructed in the use of a syringe driver, infusion techniques, the keeping of a treatment diary, and measures to be taken in case of severe adverse events. Once the patient is familiar with the method and no unacceptable side effects have been observed during the training phase, the treatment may be continued at home by the patient or carer.

Intravenous administration is contraindicated and if accidental administration into a blood vessel occurs the patient could develop shock.

Pregnancy and Lactation

Pregnancy

Use normal human immunoglobulin with caution in pregnancy.

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

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 (Briggs 2015, Schaefer 2015).

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 normal human immunoglobulin with caution in breastfeeding.

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.

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.

LactMed (2018), state that no serious adverse effects have been reported in infants whose mothers were treated with immunoglobulins, 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

Counselling

The patient should be instructed in the use of a syringe driver, infusion techniques, the keeping of a treatment diary, and measures to be taken in case of severe adverse events.

Advise patient to record the name and batch number of each administered product.

Some formulations contain high amounts of sodium.

Side Effects

Abdominal pain
Allergic reaction
Anaphylactic shock
Anti-GAD antibody positive
Anxiety
Arthralgia
Aseptic meningitis
Back pain
Blood pressure changes
Bruising at injection site
Burning sensation
Chest tightness
Chills
Diarrhoea
Dizziness
Fatigue
Fever
Flushing
Haemolytic anaemia
Headache
Hyperhidrosis
Hypersensitivity reactions
Hypertension
Hypotension
Influenza-like syndrome
Infusion related reaction
Itching (injection site)
Local pain (injection site)
Migraine
Mouth ulcers
Muscle spasm
Muscle weakness
Musculoskeletal pain
Myalgia
Nausea
Oedema (injection site)
Pain
Paraesthesia
Positive Coombs test
Pruritus
Pyrexia
Rash at injection site
Sensation of cold
Somnolence
Stiffness
Swelling (injection site)
Tachycardia
Tremor
Urticaria
Vomiting

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 for red cell antibodies for example the direct anti-globulin test (DAT, direct 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 ).

Further Information

Last Full Review Date: April 2016

Reference Sources

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 3rd edition (2015) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.

Summary of Product Characteristics: Cuvitru 200mg/ml solution for subcutaneous injection. Baxalta UK Ltd. Revised March 2021.

Summary of Product Characteristics: Hizentra 200mg/ml solution for subcutaneous injection. CSL Behring UK Ltd. Revised February 2020.

NICE Evidence Services Available at: www.nice.org.uk
Last accessed: 08 November 2018

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Globulin, Immune. Last revised: 31 October 2018
Last accessed: 08 November 2018

Immunisation against infectious disease - The Green Book.
Available at: https://www.gov.uk/government/collections/immunisation-against-infectious-disease-the-green-book
Last accessed: 08 November 2018