Side-effects of immunoglobulins include malaise, chills, Immunoglobulins
14.5 Side-effects of immunoglobulins include malaise, chills, Immunoglobulins
fever, and rarely anaphylaxis. Human immunoglobulins have replaced immunoglobu-
Uses Normal immunoglobulin is administered by lins of animal origin (antisera) which were frequently
intramuscular injection for the protection of susceptible associated with hypersensitivity. Injection of immuno-
contacts against hepatitis A virus (infectious hepatitis), globulins produces immediate protection lasting for
measles and, to a lesser extent, rubella. several weeks.
Special formulations of immunoglobulins for intra- Immunoglobulins are produced from pooled human
venous administration are available for replacement ther- plasma or serum, and are tested and found non-reactive
apy for patients with congenital agammaglobulinaemia for hepatitis B surface antigen and for antibodies against
and hypogammaglobulinaemia, for the treatment of hepatitis C virus and human immunodeficiency virus
idiopathic thrombocytopenic purpura and Kawasaki (types 1 and 2)
syndrome, and for the prophylaxis of infection following The two types of human immunoglobulin preparation
bone-marrow transplantation and in children with are normal immunoglobulin and specific immunoglo-
symptomatic HIV infection who have recurrent bacter- bulins.
ial infections. Normal immunoglobulin may also be given intramuscularly or subcutaneously for replace-
Further information about immunoglobulins is included ment therapy, but intravenous formulations are nor- in Immunisation against Infectious Disease (see section
mally preferred.
14.1), in the Health Protection Agency’s Immunoglobulin Handbook www.hpa.org.uk , and in the Department of
Intravenous immunoglobulin is also used in the treat- Health’s Clinical Guidelines for Immunoglobulin use
ment of Guillain-Barre´ syndrome in preference to www.dh.gov.uk .
plasma exchange.
Hepatitis A Hepatitis A vaccine is preferred for Availability Normal immunoglobulin is available individuals at risk of infection (see p. 668) including from Health Protection and microbiology laboratories
those visiting areas where the disease is highly endemic only for contacts and the control of outbreaks. It is
(all countries excluding Northern and Western Europe, available commercially for other purposes.
North America, Japan, Australia, and New Zealand). In Specific immunoglobulins are available from Health
unimmunised individuals, transmission of hepatitis A is Protection and microbiology laboratories with the
reduced by good hygiene. Intramuscular normal exception of tetanus immunoglobulin which is distrib-
immunoglobulin is no longer recommended for routine uted through BPL to hospital pharmacies or blood
prophylaxis in travellers but it may be indicated for transfusion departments and is also available to general
immunocompromised patients if their antibody medical practitioners. Rabies immunoglobulin is avail-
response to vaccine is unlikely to be adequate. able from the Specialist and Reference Microbiology
Intramuscular normal immunoglobulin is of value in the Division, Health Protection Agency. The large amounts
prevention of infection in close contacts of confirmed of hepatitis B immunoglobulin required by transplant
cases of hepatitis A where there has been a delay of centres should be obtained commercially.
more than 7 days in identifying contacts, or for close In Scotland all immunoglobulins are available from the
contacts at high risk of severe disease. Blood Transfusion Service . Tetanus immunoglobulin is
distributed by the Blood Transfusion Service to hospitals Measles Intramuscular normal immunoglobulin may and general medical practitioners on demand.
be given to prevent or attenuate an attack of measles in individuals who do not have adequate immunity. Chil- dren and adults with compromised immunity who have
Normal immunoglobulin come into contact with measles should receive intra-
muscular normal immunoglobulin as soon as possible Human normal immunoglobulin (‘HNIG’) is prepared from pools of at least 1000 donations of human plasma; it contains
after exposure. It is most effective if given within 72
antibody to measles, mumps, varicella, hepatitis A, and other hours but can be effective if given within 6 days. For viruses that are currently prevalent in the general population.
individuals receiving intravenous immunoglobulin, 100 mg/kg given within 3 weeks before measles expo-
Immunologic
Cautions and side-effects Normal immunoglobulin sure should prevent measles. Intramuscular normal is contra-indicated in patients with known class-speci-
immunoglobulin should also be considered for the fol- fic antibody to immunoglobulin A (IgA).
lowing individuals if they have been in contact with a confirmed case of measles or with a person associated
CHM advice with a local outbreak:
al
Intravenous normal immunoglobulin may very
non-immune pregnant women;
prod
rarely induce thromboembolic events and should
infants under 9 months.
be used with caution in those with risk factors for Further advice should be sought from the Centre for
ucts
arterial or venous thrombotic events and in obese Infections, Health Protection Agency (tel. (020) 8200 individuals.
and
Individuals with normal immunity who are not in the Normal immunoglobulin may interfere with the
above categories and who have not been fully immu-
vac
immune response to live virus vaccines which should nised against measles, can be given MMR vaccine
cines
therefore only be given at least 3 weeks before or 3 (section 14.4) for prophylaxis following exposure to months after an injection of normal immunoglobulin
measles.
(this does not apply to yellow fever vaccine since normal immunoglobulin does not contain antibody to
Rubella Intramuscular immunoglobulin after exposure this virus).
to rubella does not prevent infection in non-immune
14.5 Immunoglobulins BNF 57 contacts and is not recommended for protection of
virus in pregnancy or who are high-risk carriers (see pregnant women exposed to rubella. It may, however,
Hepatitis B Vaccine, p. 669). reduce the likelihood of a clinical attack which may
Following exposure of an unimmunised individual to an possibly reduce the risk to the fetus. It should be used
animal in or from a high-risk country, the site of the bite only if termination of pregnancy would be unacceptable
should be washed with soapy water and specific rabies to the pregnant woman, when it should be given as soon
immunoglobulin of human origin administered; as as possible after exposure. Serological follow-up of
much of the dose as possible should be injected in recipients is essential to determine if the woman has
and around the cleansed wound. Rabies vaccine should become infected despite receiving immunoglobulin. For
also be given (for details see Rabies Vaccine, p. 677). routine prophylaxis, see MMR vaccine (p. 672).
For the management of tetanus-prone wounds, tetanus For intramuscular use
immunoglobulin of human origin (‘HTIG’) should be Normal Immunoglobulin A used in addition to wound cleansing and, where appro-
Normal immunoglobulin injection. 250-mg vial; 750- priate, antibacterial prophylaxis and a tetanus-contain- mg vial
ing vaccine (section 14.4). Tetanus immunoglobulin, Dose by deep intramuscular injection , to control outbreaks of
together with metronidazole (section 5.1.11) and hepatitis A (see notes above), 500 mg; CHILD under 10 years
wound cleansing, should also be used for the treatment 250 mg
of established cases of tetanus. Measles prophylaxis, CHILD under 1 year 250 mg, 1–2 years 500 mg, 3 years and over 750 mg
Varicella–zoster immunoglobulin (VZIG) is recom- Rubella in pregnancy, prevention of clinical attack, 750 mg
mended for individuals who are at increased risk of Available from the Centre for Infections and other regional Health
severe varicella and who have no antibodies to vari- Protection Agency offices (for contacts and control of outbreaks
cella–zoster virus and who have significant exposure to only, see above)
chickenpox or herpes zoster. Those at increased risk For subcutaneous use
include: Subcuvia c (Baxter) A .
neonates whose mothers develop chickenpox in the Normal immunoglobulin injection, net price 5-mL vial
period 7 days before to 7 days after delivery; = £32.56, 10-mL vial = £65.12
susceptible neonates exposed in the first 7 days of Dose by subcutaneous injection , antibody deficiency syn-
life;
dromes, consult product literature Note May be administered by intramuscular injection (if subcu-
susceptible neonates or infants exposed whilst taneous route not possible) but not for patients with thrombocy-
requiring intensive or prolonged special care nur- topenia or other bleeding disorders
sing; cines Subgam c (BPL) A . susceptible women exposed at any stage of
vac
Normal immunoglobulin injection, net price 250-mg pregnancy (but when supplies of VZIG are short, vial = £11.20, 750-mg vial = £28.50, 1.5-g vial =
may only be issued to those exposed in the first 20
and
£57.00 weeks’ gestation or to those near term) providing Dose by subcutaneous injection , antibody deficiency syn-
VZIG is given within 10 days of contact; dromes, consult product literature
immunosuppressed individuals including those who
oducts
Note May be administered by intramuscular injection (if subcu- have received corticosteroids in the previous 3
pr
taneous route not possible) but not for patients with thrombocy- topenia or other bleeding disorders
months at the following dose equivalents of pred-
al
nisolone; children 2 mg/kg daily for at least 1 week Vivaglobin c (CSL Behring) A or 1 mg/kg daily for 1 month; adults about 40 mg
Normal immunoglobulin injection, net price 3-mL vial daily for more than 1 week. = £17.76, 10-mL vial = £59.20, 20-mL vial = £118.40
Important: for full details consult Immunisation against
unologic
Dose by subcutaneous injection , antibody deficiency syn- Infectious Disease . Varicella–zoster vaccine is avail- dromes, consult product literature
able—see section 14.4.
Imm
14 Normal Immunoglobulin for Intravenous Use
For intravenous use
Hepatitis B
A See notes above Gammagard S/D (0.5 g, 2.5 g, 5 g, 10 g); Octagam T (5%—2.5 g,
Hepatitis B Immunoglobulin A Brands include Flebogamma
5% (0.5 g, 2.5 g, 5 g, 10 g);
Dose by intramuscular injection (as soon as possible after 5 g, 10 g; 10%—5 g, 10 g); Privigen T (5 g, 10 g, 20 g);
exposure; ideally within 12 hours, but no later than 7 days after Sandoglobulin
NF Liquid (6 g, 12 g); Vigam S (2.5 g, 5 g); exposure), ADULT and CHILD over 10 years 500 units; CHILD under Vigam Liquid (2.5 g, 5 g, 10 g)
5 years 200 units, 5–9 years 300 units; NEONATE 200 units as soon Dose consult product literature
as possible after birth; for full details consult Immunisation against Infectious Disease Available from selected Health Protection Agency and NHS laboratories (except for Transplant Centres, see p. 681), also available from BPL
Specific immunoglobulins
Note Hepatitis B immunoglobulin for intravenous use is available from BPL on a named-patient basis
Specific immunoglobulins are prepared by pooling the plasma of selected donors with high levels of the spe-
Rabies
cific antibody required. Rabies Immunoglobulin A Although a hepatitis B vaccine is now available for those
(Antirabies Immunoglobulin Injection) at high risk of infection, specific hepatitis B immuno-
See notes above globulin (‘HBIG’) is available for use in association with
20 units/kg by infiltration in and around the cleansed hepatitis B vaccine for the prevention of infection in
Dose
wound; if wound not visible or healed or if infiltration of whole laboratory and other personnel who have been acciden-
volume not possible, give remainder by intramuscular injection tally inoculated with hepatitis B virus, and in infants into anterolateral thigh (remote from vaccination site)
born to mothers who have become infected with this Available from Specialist and Reference Microbiology Division, Health Protection Agency (also from BPL)
BNF 57
14.5 Immunoglobulins 683
Tetanus Anti-D (Rh ) Immunoglobulin A Tetanus Immunoglobulin A Injection , anti-D (Rh ) immunoglobulin, net price (Antitetanus Immunoglobulin Injection)
250-unit vial = £19.00, 500-unit vial = £27.00, 1500- See notes above
unit vial = £58.00, 2500-unit vial = £94.40 Dose by intramuscular injection , prophylactic 250 units,
Dose by deep intramuscular injection , to rhesus-negative increased to 500 units if more than 24 hours have elapsed or there
woman for prevention of Rh (D) sensitisation: is risk of heavy contamination or following burns
Following birth of rhesus-positive infant, 500 units immediately or Therapeutic, 150 units/kg (multiple sites)
within 72 hours; for transplacental bleed of over 4 mL fetal red Available from BPL
cells, extra 100–125 units per mL fetal red cells Note May be difficult to obtain
Following any potentially sensitising episode (e.g. stillbirth, abor- Varicella–zoster
tion, amniocentesis) up to 20 weeks’ gestation 250 units per Varicella–Zoster Immunoglobulin episode (after 20 weeks, 500 units) immediately or within 72 hours A Antenatal prophylaxis, 500 units given at weeks 28 and 34 of (Antivaricella–zoster Immunoglobulin)
pregnancy; if infant rhesus-positive, a further dose is still needed See notes above
immediately or within 72 hours of delivery Dose by deep intramuscular injection , prophylaxis (as soon as
Following Rh (D) incompatible blood transfusion, 100–125 units possible—not later than 10 days after exposure), NEONATE ,
per mL transfused rhesus-positive red cells INFANT and CHILD up to 5 years 250 mg, 6–10 years 500 mg, 11–14
Note Subcutaneous route used for patients with bleeding disorders years 750 mg, over 15 years 1 g; give second dose if further
Available from Blood Centres and from BPL (D-Gam ) exposure occurs more than 3 weeks after first dose Note No evidence that effective in treatment of severe disease.
Partobulin SDF c (Baxter) A Normal immunoglobulin for intravenous use may be used in those
Injection , anti-D (Rh ) immunoglobulin 1250 units/ unable to receive intramuscular injections Available from selected Health Protection Agency and NHS
mL (250 micrograms/mL), net price 1-mL prefilled laboratories (also from BPL)
syringe = £35.00 Dose by intramuscular injection , to rhesus-negative woman for
Anti-D (Rh prevention of Rh (D) sensitisation:
Following birth of rhesus-positive infant, 1000–1650 units imme- Anti-D (Rh ) immunoglobulin is available to prevent a
0 ) immunoglobulin
diately or within 72 hours; for large transplacental blood loss, 50– 125 units per mL of fetal red cells
rhesus-negative mother from forming antibodies to fetal Antenatal prophylaxis, 1000–1650 units given at weeks 28 and 34 rhesus-positive cells which may pass into the maternal
of pregnancy; if infant rhesus-positive, further dose is needed circulation. The objective is to protect any subsequent
immediately or within 72 hours of delivery child from the hazard of haemolytic disease of the new-
Following abortion, ectopic pregnancy or hydatidiform mole up to born.
12 weeks’ gestation, 600–750 units (after 12 weeks, 1250–1650 units) immediately or within 72 hours
Anti-D immunoglobulin should be administered follow- Following amniocentesis or chorionic villous sampling, 1250– ing any sensitising episode (e.g. abortion, miscarriage
1650 units immediately or within 72 hours and birth); it should be injected within 72 hours of the
Following Rh (D) incompatible blood or red cell transfusion, episode but even if a longer period has elapsed it may
1250 units per 10 mL of transfused rhesus-positive red cells immediately or within 72 hours
still give protection and should be administered. The Note Subcutaneous route used for patients with bleeding disorders. dose of anti-D immunoglobulin is determined according to the level of exposure to rhesus-positive blood.
Rhophylac c (CSL Behring) A For routine antenatal prophylaxis (see also NICE gui-
Injection , anti-D (Rh ) immunoglobulin 750 units/mL dance below), two doses of at least 500 units of anti-D
(150 micrograms/mL), net price 2-mL (1500-unit) immunoglobulin should be given, the first at 28 weeks’
prefilled syringe = £46.50. gestation and the second at 34 weeks; alternatively a
Dose by intramuscular or intravenous injection , to rhesus- single dose of 1500 units given between 28 and 30 negative woman for prevention of Rh (D) sensitisation: Following birth of rhesus-positive infant, 1000–1500 units imme- weeks gestation can be used.
diately or within 72 hours; for large transplacental bleed, extra 100 units per mL fetal red cells (preferably by intravenous injec-
NICE guidance
tion)
Following any potentially sensitising episode (e.g. abortion,
rhesus-negative women (August 2008) amniocentesis, chorionic villous sampling) up to 12 weeks’
Routine antenatal anti-D prophylaxis for
gestation 1000 units per episode (after 12 weeks, higher doses
Routine antenatal anti-D prophylaxis should be may be required) immediately or within 72 hours offered to all non-sensitised pregnant women who
Antenatal prophylaxis, 1500 units given between weeks 28–30 of
Immunologic
are rhesus negative. pregnancy; if infant rhesus-positive, a further dose is still needed Use of routine antenatal anti-D prophylaxis should immediately or within 72 hours of delivery Following Rh (D) incompatible blood transfusion, by intravenous not be affected by previous anti-D prophylaxis for a
injection , 50 units per mL transfused rhesus-positive blood (or sensitising event early in the same pregnancy. Simi-
100 units per mL of erythrocyte concentrate) larly, postpartum anti-D prophylaxis should not be
Note Intravenous route used for patients with bleeding disorders. affected by previous routine antenatal anti-D
c al
WinRho SDF (Baxter) A prod
prophylaxis or by antenatal anti-D prophylaxis for
a sensitising event. Injection , anti-D (Rh ) immunoglobulin, powder for reconstitution, net price 1500-unit (300-microgram)
ucts
vial (with diluent) = £313.50, 5000-unit (1-mg) vial (with diluent) = £1045.00
and
Note
Dose to rhesus-negative woman for prevention of Rh (D) sensi-
MMR vaccine may be given in the postpartum
tisation: Following birth of rhesus-positive infant, by intramuscular injec-
vac
period with anti-D (Rh ) immunoglobulin injection provided that separate syringes are used and the
tion , 1500 units or by intravenous injection , 600 units immediately
cines
products are administered into different limbs. If or within 72 hours; for transplacental bleed of over 25 mL fetal
blood, by intramuscular or intravenous injection blood is transfused, the antibody response to the , extra 50 units
per mL fetal blood (further doses required for large bleed) vaccine may be inhibited—measure rubella anti-
Following any potentially sensitising episode (e.g. abortion, bodies after 6–8 weeks and revaccinate if necessary.
amniocentesis, chorionic villous sampling) up to 12 weeks’ gestation, by intramuscular or intravenous injection , 600 units per
14.6 International travel BNF 57
episode (after 12 weeks, 1500 units) immediately or within 72 hours
in non-European areas surrounding the Mediterranean, Antenatal prophylaxis, by intramuscular or intravenous injection ,
in Africa, the Middle East, Asia, and South America. 1500 units given at week 28 of pregnancy; if infant rhesus positive;
Travellers to areas that have a high incidence of polio- a further dose is still needed immediately or within 72 hours of delivery
myelitis or tuberculosis should be immunised with the Following Rh (D) incompatible blood transfusion, by intravenous
appropriate vaccine; in the case of poliomyelitis pre- injection , 50 units per mL transfused rhesus-positive blood (or
viously immunised adults may be given a booster dose 100 units per mL of erythrocyte concentrate); if intramuscular
of a preparation containing inactivated poliomyelitis route used give in divided doses over several days
vaccine (see p. 676). BCG immunisation (see p. 664) is Following Rh (D) incompatible thrombocyte transfusion in
recommended for travellers aged under 35 years 1 pro- rhesus-negative female child or woman of child-bearing age, by intravenous injection , 600 units
posing to stay for longer than 3 months (or in close Autoimmune (idiopathic) thrombocytopenic purpura, consult
contact with the local population) in countries with an product literature
incidence of tuberculosis greater than 40 per 100 000 2 ; it Note Intravenous route used for patients with bleeding disorders
should preferably be given three months or more before departure.
Yellow fever immunisation (see p. 680) is recommended
Interferons
for travel to the endemic zones of Africa and South Interferon gamma-1b is licensed to reduce the fre-
America. Many countries require an International Certi- quency of serious infection in chronic granulomatous
ficate of Vaccination from individuals arriving from, or disease and in severe malignant osteopetrosis.
who have been travelling through, endemic areas, whilst other countries require a certificate from all entering travellers (consult the Department of Health handbook,
INTERFERON GAMMA-1b
Health Information for Overseas Travel , www.dh.gov.uk ). (Immune interferon)
Immunisation against meningococcal meningitis is Indications see notes above
recommended for a number of areas of the world (for Cautions severe hepatic impairment (Appendix 2),
details, see p. 673). renal impairment (Appendix 3); seizure disorders
Protection against hepatitis A is recommended for (including seizures associated with fever); cardiac
travellers to high-risk areas outside Northern and Wes- disease (including ischaemia, congestive heart failure,
tern Europe, North America, Japan, Australia and New and arrhythmias); monitor before and during treat-
Zealand. Hepatitis A vaccine (see p. 668) is preferred ment: haematological tests (including full blood count,
and it is likely to be effective even if given shortly before
cines
differential white cell count, and platelet count), blood departure; normal immunoglobulin is no longer given chemistry tests (including renal and liver function
vac routinely but may be indicated in the immunocompro-
tests) and urinalysis; avoid simultaneous administra- mised (see p. 681). Special care must also be taken with tion of foreign proteins including immunological
and food hygiene (see below).
products (risk of exaggerated immune response); Hepatitis B vaccine (see p. 669) is recommended for pregnancy (Appendix 4); breast-feeding (Appendix 5);
those travelling to areas of high or intermediate pre-
oducts interactions: Appendix 1 (interferons)
Driving valence who intend to seek employment as healthcare
pr May impair ability to drive or operate machinery;
effects may be enhanced by alcohol workers or who plan to remain there for lengthy periods al Side-effects nausea, vomiting; headache, fatigue,
and who may therefore be at increased risk of acquiring fever; myalgia, arthralgia; rash, injection-site reac-
infection as the result of medical or dental procedures tions; rarely confusion and systemic lupus erythe-
carried out in those countries. Short-term tourists or matosus; also reported, neutropenia, thrombocyto-
business travellers are not generally at increased risk of
unologic
penia, and raised liver enzymes infection but may place themselves at risk by their Dose
sexual behaviour when abroad.
Imm
. See under Preparations Prophylactic immunisation against rabies (see p. 677) is
14 recommended for travellers to enzootic areas on long
Immukin c (Boehringer Ingelheim) A journeys or to areas out of reach of immediate medical Injection , recombinant human interferon gamma-1b
attention.
200 micrograms/mL, net price 0.5-mL vial = £88.00 Dose by subcutaneous injection , 50 micrograms/m 3 times a
Travellers who have not had a tetanus booster in the week; patients with body surface area of 0.5 m or less, 1.5 micr-
last 10 years and are visiting areas where medical ograms/kg 3 times a week; not yet recommended for children
attention may not be accessible should receive a boos- under 6 months with chronic granulomatous disease
ter dose of adsorbed diphtheria [low dose], tetanus and inactivated poliomyelitis vaccine (see p. 665), even if they have received 5 doses of a tetanus-containing vaccine previously.