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.