D-GAM ^®, Human Anti-D Immunoglobulin, 1,500 and 2,500 IU, solution for injection.

Human Anti-D Immunoglobulin Ph.Eur.*

Each vial contains: 5 - 50 mg/L protein (250 and 500 IU vials) or 20 - 180 mg/L protein (1,500 and 2,500 IU vials) of which at least 95% is gammaglobulin (IgG). The product contains less than 0.02% w/w of IgA. For excipients see 6.1. The product is prepared from plasma from RhD-negative screened donors who have been immunised against RhD antigen and contains specific antibodies against erythrocyte RhD antigen. Donors are selected from the USA.

* The product is presented in three different concentrations but the highest concentration is filled in different volumes to achieve two dose presentations. The product is therefore available in four nominal doses, namely 250 IU per vial, 500 IU per vial, 1,500 IU per vial and 2,500 IU per vial.

A solution for injection.

Prevention of RhD immunisation in RhD negative women:

i. Pregnancy/delivery of a RhD positive baby.

ii. Abortion/threatened abortion, ectopic pregnancy or hydatidiform mole.

iii. After ante-partum haemorrhage (APH), amniocentesis, chorionic biopsy or obstetric manipulative procedure e.g. external version, or abdominal trauma, which may cause transplacental haemorrhage (TPH).

Treatment of RhD negative patients after transfusions of RhD positive blood or other products containing RhD positive red blood cells (e.g. platelets).

Posology

a) Post-Natal Dosage:

The recommended dose is 500 IU.

For postnatal use, the product should be administered as soon as possible within 72 hours of delivery.

If a large fetomaternal haemorrhage is suspected, its extent should be determined by a suitable method and additional doses of anti-D should be administered as indicated.

b) Ante-Natal Prophylaxis:

500 IU given at both 28 and 34 weeks of gestation or a single dose of 1,500 IU at 28 weeks of gestation.

c) Following a Potentially Sensitising Event During Pregnancy:

D-GAM ^® should be administered as soon as possible and no later than 72 hours after the event.

Up to 20 weeks gestation: recommended dose is 250 IU per incident.

After 20 weeks gestation: recommended dose is 500 IU per incident. A test for the size of the FMH should be performed when anti-D is given after 20 weeks and additional doses of anti-D should be administered as indicated.

d) Prevention of Immunisation in RhD Negative Patients Given Blood Components Containing RhD Positive Cells:

Recommended doses: 125 IU per mL of transfused RhD positive red cells; 250 IU per three adult doses of platelets.

Method of administration

For intramuscular use (preferably into the deltoid muscle).

D-GAM ^® vials are for single use only.

In the case of haemorrhagic disorders, where intramuscular injections are contra-indicated, Anti-D immunoglobulin may be administered subcutaneously. Careful manual pressure with a compress should be applied to the site after injection.

If large total doses (>5 mL) are required, it is advisable to administer them in divided doses at different sites.

Hypersensitivity to any of the components.

Do not administer this product intravenously (risk of shock).

In the case of post-partum use, the product is intended for maternal administration. It should not be given to the newborn infant.

The product is not intended for use in RhD positive individuals.

Patients should be observed for at least 20 minutes after administration.

If symptoms of allergic or anaphylactic type reactions occur, immediate discontinuation of the administration is required.

True hypersensitivity reactions are rare but allergic type responses to Anti-D immunoglobulin may occur. Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, wheezing, hypotension and anaphylaxis. The treatment required depends on the nature and severity of the side effect. In case of shock, the current medical standards for shock treatment should be observed.

D-GAM ^® contains a small quantity of IgA. Although anti-D immunoglobulin has been used successfully to treat selected IgA deficient individuals, the attending physician must weigh the benefit against the potential risks of hypersensitivity reactions. Individuals deficient in IgA have a potential for development of IgA antibodies and anaphylactic reactions after administration of blood components containing IgA.

Standard measures to prevent infections resulting from the use of medicinal products prepared from human blood or plasma include selection of donors, screening of individual donations and plasma pools for specific markers of infection and the inclusion of effective manufacturing steps for the inactivation/removal of viruses. Despite this, when medicinal products prepared from human blood or plasma are administered, the possibility of transmitting infective agents cannot be totally excluded. This also applies to unknown or emerging viruses and other pathogens.

The viral removal/inactivation procedures may be of limited value against non-enveloped viruses such as hepatitis A virus or parvovirus B19.

In the interest of patients, it is recommended that, whenever possible, every time that D-GAM ^® is administered to them, the name and batch number of the product is registered.

Active immunisation with live virus vaccines (e.g. measles, mumps or rubella) should be postponed until 3 months after the administration of Anti-D immunoglobulin, as the efficacy of the live virus vaccine may be impaired. If Anti-D immunoglobulin needs to be administered within 2-4 weeks of a live virus vaccination, then the efficacy of such a vaccination may be impaired.

After injection 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.

The results of blood typing and antibody testing, including the Coombs' or antiglobulin test, are significantly affected by the administration of anti-D immunoglobulin.

This medicinal product is used in pregnancy.

No effects on ability to drive and use machines have been observed.

Local pain and tenderness can be observed at the injection site; this can be prevented by dividing larger doses over several injection sites.

The following side effects are known to be associated with Anti-D (the incidence has not been quantified): Occasionally fever, malaise, headache, cutaneous reactions and chills occur. In rare cases: nausea, vomiting, hypotension, tachycardia and allergic or anaphylactic type reactions, including dyspnoea and shock, are reported, even when the patient has shown no hypersensitivity to previous administration.

For information on viral safety see 4.4.

No data are available on overdosage. RhD negative patients who are given RhD positive blood or other products containing RhD positive red blood cells and receive anti-D immunoglobulin should be monitored clinically and by biological parameters, because of the risk of haemolytic reaction.

In other RhD negative individuals, overdosage should not lead to more frequent or more severe undesirable effects than the normal dose.

Pharmacotherapeutic group: immune sera and immunoglobulins: Anti-D (Rh) immunoglobulin. ATC code: J06B B01.

Anti-D immunoglobulin contains specific antibodies (IgG) against the RhD antigen of human erythrocytes.

Measurable levels of antibodies are obtained approximately 8 hours after intramuscular injection. Peak serum levels are usually achieved 2 to 4 days later.

The half-life in the circulation of individuals with normal IgG levels is 3 to 5 weeks.

IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.

D-GAM ^® is a preparation of human plasma proteins, so safety testing in animals is not particularly relevant to the safety of use in man. Acute toxicity studies in rat and mouse showed species specific reactions, which bear no relevance to administration in humans.

Repeated dose safety testing is impracticable due to the induction of and interference with antibodies to human protein. Clinical experience provides no sign of tumourigenic and mutagenic effects.

Sodium chloride

Glycine

Sodium acetate trihydrate

Sodium hydroxide

This medicinal product must not be mixed with other medicinal products.

D-GAM ^® should be stored in the original container at 2°C to 8°C. Storage for up to one week at ambient temperatures (25°C) in the original container is not detrimental. DO NOT FREEZE.

The condition of date-expired, or incorrectly stored product cannot be guaranteed. Such product may be unsafe, and should not be used.

Neutral borosilicate glass vial (Type I Ph.Eur.) with overseal consisting of a halobutyl rubber wad (Type I Ph.Eur.), clear lacquered aluminium skirt and flip-off polypropylene cap.

The product should be brought to room or body temperature before use.

The solution should be clear or slightly opalescent. Do not use solutions which are cloudy or have deposits.

Any unused product or waste material should be disposed of in accordance with local requirements.

Bio Products Laboratory

Dagger Lane

Elstree

Hertfordshire

WD6 3BX

United Kingdom.

PL 08801/0049 - 1,500 IU and 2,500 IU dose sizes.

31 July 2000