Immunoglobulin human normal intravenous
- Drugs List
- Therapeutic Indications
- Dosage
- Administration
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Infusions containing human normal immunoglobulin.
Drugs List
Therapeutic Indications
Uses
Chronic inflammatory demyelinating polyneuropathy (CIDP)
Common variable immunodeficiency (replacement therapy)
Congenital agammaglobulinaemia - replacement therapy
Congenital HIV with recurrent bacterial infections: Replacement therapy
Congenital hypogammaglobulinaemia - replacement therapy
Dermatomyositis
Idiopathic thrombocytopenic purpura
Immunomodulatory effect in bone marrow transplantation
Infection prophylaxis after bone marrow transplantation
Kawasaki syndrome
Multifocal motor neuropathy (MMN)
Myasthenia gravis
Primary immunodeficiency syndromes with impaired antibody production
Prophylactic use in children with HIV + recurrent bacterial infections
Secondary hypogammaglobulinaemia in CLL or Myeloma with recurrent infection
Secondary immunodeficiencies with severe or recurrent infections
Severe combined immunodeficiencies (replacement therapy)
Treatment of Guillain Barre Syndrome
Treatment of hypogammaglobulinaemia after stem cell transplant
Wiskott Aldrich syndrome
Dosage
Antibody titres for some common antigens and pathogens can vary widely not only between products from different manufacturers, but also from lot to lot. Formulations of intravenous immunoglobulins should not therefore be regarded as equivalent.
The dose and dosage regime is dependent on the indication and on the in vivo half life in individual patients.
Not all brands are licensed for all indications, refer to specific product literature.
In replacement therapy the dosage may need to be individualised for each patient depending on response. The following dosage regimes are given as a guideline.
Adults
Replacement therapy in immunodeficiencies
The regimen should achieve a trough level of immunoglobulin G (IgG), measured before the next infusion, of at least 4 to 6g/litre. Treatment period to equilibrium may be 3 to 6 months.
A starting dose of 0.4 to 0.8g/kg followed by at least 0.2g/kg every three to four weeks is recommended.
The dose required to achieve a trough level of 5 to 6g/litre is usually within the range 0.2 to 0.8g/kg every three to four weeks.
When a steady state has been reached the frequency of injections varies between 2 to 4 weeks.
Trough levels should be measured in order to adjust the dose and dosage interval.
Secondary immunodeficiencies in patients with severe or recurrent infections, ineffective antimicrobial treatment and either proven specific antibody failure or serum level of less than 4g/litre
0.2g/kg to 0.4g/kg every three to four weeks.
Trough levels should be measured in conjunction with incidence of infection.
Dose to be adjusted as necessary to achieve optimal protection against infection.
Replacement therapy in myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections and congenital HIV infection with recurrent bacterial infections
0.2 to 0.4g/kg every 3 to 4 weeks.
Hypogammaglobulinaemia after allogeneic haematopoietic stem cell transplantation
0.2 to 0.4g/kg every three to four weeks. Trough levels should be maintained above 5g/litre.
Idiopathic Thrombocytopenic Purpura
For the treatment of an acute episode give 0.8 to 1g/kg on day one, which may be repeated once within 3 days, or 0.4g/kg daily for 2 to 5 days.
The treatment can be repeated if relapse occurs.
The mean duration of platelet response is 6 days in chronic ITP patients. Monitoring of platelet counts from day 7 onwards is recommended for patients with clinical symptoms, especially active bleedings.
Kawasaki Disease
1.6 to 2g/kg in divided doses over 2 to 5 days, or 2g/kg as a single dose.
Patients should receive concurrent aspirin.
Allogeneic Bone Marrow Transplantation
Human normal immunoglobulin may be used as part of the conditioning regimen and after the transplant.
For the treatment of infections and prophylaxis of graft versus host disease, dose is individually tailored.
The starting dose is normally 0.5g/kg/week starting 7 days before transplantation and for up to 3 months after transplantation.
In case of persistent lack of antibody production, a dosage of 0.5g/kg/month is recommended until the antibody level returns to normal.
Guillain Barre Syndrome
0.4g/kg/day for 5 days. Repeated at 4 week intervals if necessary.
Multifocal Motor Neuropathy (MMN)
Starting dose: 2g/kg for 2 to 5 days
Maintenance dose: 1g/kg every 2 to 4 weeks, or 2g/kg every 4 to 8 weeks.
Chronic Inflammatory Demyelinating Polyneuropathy (CIPD)
Loading dose: 2g/kg (20ml/kg) in divided doses over up to 5 consecutive days.
Maintenance dose: 1g/kg administered over 1 day (10ml/kg) or divided into two doses of 0.5g/kg (5ml/kg) given on two consecutive days, every 3 weeks.
Severe acute exacerbation of myasthenia gravis
2g/kg over 2 consecutive days (dose of 1g/kg per day).
Dermatomyositis (DM)
2g/kg every 4 weeks, divided in equal doses given over 2 to 5 consecutive days.
Some manufacturers advise adapting the dose according to individual clinical response.
Children
See specialist literature
Not all formulations are licensed in all age groups. The dosage in children is not different from that of adults as the dosage for each indication is given by body weight and adjusted to the clinical outcome of the condition.
Myasthenia Gravis
Contraindicated in children under 18 years.
Guillain Barre Syndrome
Experience in children is limited.
Chronic Inflammatory Demyelinating Polyneuropathy (CIPD)
Experience in children is limited.
Patients with Renal Impairment
Acute renal failure has occurred following immunoglobulin treatment and is more likely in patients with pre-existing renal impairment. Ensure the product is administered at the minimum rate of infusion and dose practicable.
Administration
For administration by intravenous infusion only.
Contraindications
Immunoglobulin A antibodies
Immunoglobulin A deficiency
Immunoglobulin A deficiency with IgA antibodies
Precautions and Warnings
Children under 18 years
Elderly
Obesity
Predisposition to developing neutropenia
Predisposition to thromboembolic disease
Prolonged immobilisation
Restricted sodium intake
Untreated infection or underlying chronic inflammation
Breastfeeding
Diabetes mellitus
Glucose-galactose malabsorption syndrome
Hereditary fructose intolerance
History of thrombosis
Hypertension
Hypovolaemia
Neutropenia
Pregnancy
Renal impairment
Thrombophilia
Vascular disorder
IVIG limits immune response to live virus vaccine given in previous 3 weeks
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
Not all available brands are licensed for all indications
Treatment to be initiated and supervised by a specialist
Derived from human plasma. Transmission of infective agents possible.
Presentations with sorbitol unsuitable in hereditary fructose intolerance
Some formulations contain glucose
Different brands of this product are not interchangeable
Do not mix with other drugs or substances
Have adrenaline injection ready for use in case of anaphylaxis
If adverse reactions occur, reduce rate or temporarily stop infusion
Monitor throughout infusion and for 1 hour post first infusion
Record name and batch number of administered product
Warm to room temperature prior to use
Ensure adequate hydration prior to infusion
Monitor for signs and symptoms of thrombosis
Monitor IgG trough levels to adjust dose and/or dose interval
Monitor patient closely for haemolysis
Monitor serum creatinine
Monitor urine output
Discontinue if signs of pulmonary distress
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
May interfere with antibody tests
Discontinue if Aseptic Meningitis Syndrome occurs
Discontinue or reduce dose if renal impairment worsens
Not licensed for all indications in all age groups
Measles vaccine may not be effective for up to 1 year after treatment
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 and for at least 20 minutes after the infusion. If this is the first infusion, or when switching product, or when there has been a long interval since the last infusion, patients should be monitored for 1 hour post infusion.
Adverse reactions may occur more frequently during high rate of infusion.
In patients at risk of thromboembolic adverse reactions, administer at the minimum rate of infusion and dose.
Aseptic meningitis has been reported to occur in association with immunoglobulin treatment. Discontinuation of treatment has resulted in remission of aseptic meningitis within several days without sequelae. The syndrome usually begins within several hours to 2 days following immunoglobulin treatment. Patients exhibiting signs and symptoms should receive a thorough neurological examination.
Some products contain L-proline and should not be used in patients with hyperprolinaemia.
Some products contain glucose. Caution is advised when administering these products, or those diluted with a 5% glucose solution, as they may interfere with determination of blood glucose levels.
Some formulations contain maltose. Some types of blood glucose testing systems may falsely interpret the maltose as glucose. This may falsely elevate glucose readings during an infusion and for 15 hours afterwards.
Acute renal failure has been reported following immunoglobulin treatment and are more likely in elderly patients. These reports have been associated with the use of products containing excipients such as glucose, maltose and particularly sucrose. Patients at high risk of acute renal failure should avoid those formulations.
Pregnancy and Lactation
Pregnancy
Use normal human immunoglobulins 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 2007).
Lactation
Use normal human immunoglobulins 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. 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.
LactMed (2018), state that no serious adverse effects had been reported in the infants breast fed by mothers treated with immunoglobulin, apart from a transient rash that occurred one day after the dose was administered to the mother.
Side Effects
Abdominal pain
Acute renal failure
Agitation
Allergic reaction
Anaemia
Anaphylactic reaction
Anaphylactic shock
Angioedema
Anisocytosis
Anorexia
Anxiety
Arthralgia
Aseptic meningitis
Asthenia
Cardiac disorders
Cerebrovascular accident
Changes in erythrocyte sedimentation rate
Chest discomfort
Chills
Circulatory failure
Convulsions
Cyanosis
Decrease in creatinine clearance
Decrease in haematocrit
Decreased appetite
Deep vein thrombosis (DVT)
Dehydration
Dizziness
Dysaesthesia
Dysgeusia
Epistaxis
Eye disorder
False positive reaction to glucose with reducing substances
Fatigue
Fever
Fluid overload
Flushing
Gastrointestinal disorder
Haemoglobin decrease
Haemolysis
Haemolytic anaemia
Headache
Hepatitis
Hypertension
Hypotension
Increase in aminotransferase level
Increase in blood urea or creatinine
Increase in lactate dehydrogenase
Infections
Influenza-like symptoms
Influenza-like syndrome
Injection site reactions
Insomnia
Leukopenia
Lymphadenopathy
Lymphopenia
Malaise
Migraine
Monocytopenia
Muscle spasm
Myalgia
Myocardial infarction
Nausea
Neutropenia
Oedema
Oropharyngeal swelling
Pain
Pallor
Palpitations
Paraesthesia
Peripheral vascular disorders
Phlebitis
Positive Coombs test
Proteinuria
Pulmonary embolism
Rash
Reduction in blood count
Respiratory disorders
Restlessness
Rigors
Rise in body temperature
Serum bilirubin increased
Sinusitis
Skin reactions
Somnolence
Stiffness
Stomatitis
Stroke
Sweating
Syncope
Tachycardia
Thrombosis
Transfusion related acute lung injury (TRALI)
Transient ischaemic attack
Tremor
Urticaria
Vertigo
Visual disturbances
Vomiting
Effects on Laboratory Tests
After infusion 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 alloantibodies (reticulocyte count, haptoglobin and Coombs test).
Some formulations contain maltose. Some types of blood glucose testing systems may falsely interpret the maltose as glucose. This may falsely elevate glucose readings during an infusion and for 15 hours afterwards.
Administration can lead to false positive readings in assays that depend on detection of beta-D-glucans for diagnosis of fungal infections. This may persist during the weeks following infusion of the product.
The erythrocyte sedimentation rate (ESR) may falsely be increased (non-inflammatory rise).
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: May 2018
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, 10th edition (2015) ed. Briggs, G., Freeman, R. Wolters Kluwer Health, Philadelphia.
Summary of Product Characteristics: Aragam 50mg/ml. Oxbridge Pharma Ltd. Revised October 2012
Summary of Product Characteristics: Flebogamma DIF 50 mg/ml. Grifols UK Ltd. Revised July 2014
Summary of Product Characteristics: Flebogamma DIF 100 mg/ml. Grifols UK Ltd. Revised December 2015
Summary of Product Characteristics: Gammagard SD 5 g powder and solvent for solution for infusion. Baxter Healthcare Ltd. Revised August 2015
Summary of Product Characteristics: Gammagard SD 10 g powder and solvent for solution for infusion. Baxter Healthcare Ltd. Revised August 2015
Summary of Product Characteristics: Gammaplex 10% 100mg/ml solution for infusion. Bio Products Laboratory Limited. Revised August 2018.
Summary of Product Characteristics: Gammaplex, a sterile liquid of 5% w/v normal immunoglobulin. Bio Products Laboratory Limited. Revised January 2015
Summary of Product Characteristics: Gamunex 10%. Grifols UK Ltd. Revised February 2020.
Summary of Product Characteristics: Intratect. Biotest (UK) Ltd. Revised February 2016
Summary of Product Characteristics: Intratect 100g/l. Biotest (UK) Ltd. Revised February 2016
Summary of Product Characteristics: IQYMUNE 100 mg/mL, solution for infusion. LFB Biopharmaceuticals Limited. Revised August 2019.
Summary of Product Characteristics: Kiovig 100 mg/ml solution for infusion. Baxalta UK Ltd. Revised September 2015
Summary of Product Characteristics: Octagam 5% solution for infusion. Octapharma Limited. Revised August 2020
Summary of Product Characteristics: Octagam 10% solution for infusion. Octapharma Limited. Revised April 2021
Summary of Product Characteristics: Panzyga 100mg/ml solution for infusion. Octapharma Limited. Revised July 2018
Summary of Product Characteristics: Privigen 100mg/ml solution for infusion. CSL Behring UK Limited. Revised January 2019.
Summary of Product Characteristics: Vigam Liquid. Bio Products Laboratory Limited. Revised October 2015
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 04 October 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: 03 June 2019
Last accessed: 22 July 2019
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