SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
GAMMA anty-D 50, 50 micrograms/ml
Solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of the solution consists of:
Human anti-D immunoglobulin 50 micrograms (250 IU)
Human protein content not less than 30 mg
Each ampoule contains 50 micrograms (250 IU) human anti-D immunoglobulin
The IgA content is not more than 50 micrograms/ml
The product is produced from the plasma of human donors.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL FORM
Solution for injection
Transparent or slightly opalescent solution.
4. CLINICAL PARTICULARS
4.1 Therapeutic indications
Prevention of immunisation with the Rh(D) agent in Rh(D) negative women
Miscarriage / risk of miscarriage, ectopic pregnancy
To be administered after labour, during pregnancy and after foetus removal over the 12th week of pregnancy, in risk of immature delivery or preterm delivery, after diagnostic amniocentesis over the 12th week of pregnancy is intended product GAMMA anty-D 150.
4.2 Posology and method of administration
The dose of anti-D immunoglobulin should be determined according to the level of exposure to Rh(D) positive red blood cells (RBCs) and based on the knowledge that 0.5 ml of packed Rh(D) positive RBCs or 1 ml of Rh(D) positive blood is neutralised by approximately 10 micrograms (50 IU) of anti-D immunoglobulin.
You should follow the instructions on usage of anti-D immunoglobulin in force in a given EU member country.
1 ampoule of the product is administered intramuscularly to 12 weeks of pregnancy within 48 hours, no later than 72 hours:
after a miscarriage,
after the termination of pregnancy,
after the removal of ectopic pregnancy (ectopic).
Method of administration
The GAMMA anty-D 50 should be administered via the intramuscular route.
In the case of coagulation disorders, when intramuscular administration is contraindicated, GAMMA anty-D 50 may be administered subcutaneously. The place of injection should be protected with tampon compression.
If a large dose of the product is required to be administered intramuscularly (over 5 ml), it is possible to be administered in doses divided for various sites.
Hypersensitivity to active substance or to any of the excipients listed in section 6.1.
Hypersensitivity to human immunoglobulins especially if the patient has anti-IgA antibodies.
4.4 Special warnings and precautions for use
Must not be administered intravenously. Ensure that GAMMA anty-D 50 is not administered into a blood vessel, because of the risk of shock.
Must not be administered in newborn babies.
Must not be administered in Rh positive (D+) women.
True hypersensitivity reactions are rare but allergic type responses to anti-D immunoglobulin may occur.
The patient should be observed for at least 20 minutes after administration.
GAMMA anty-D 50 contains a small quantity of IgA. Although anti-D immunoglobulin has been used successfully in selected IgA deficient individuals, individuals who are deficient in IgA have the potential for developing IgA antibodies and may have anaphylactic reactions after administration of plasma derived medicinal products containing IgA. The physician must therefore weigh the benefit of treatment with GAMMA anty-D 50 against the potential risk of hypersensitivity reactions.
Rarely, human anti-D immunoglobulin can induce a fall in blood pressure with anaphylactic reaction, even in patients who have tolerated previous treatment with human immunoglobulin.
Patients should be informed of the early signs of hypersensitivity reactions including hives, generalised urticaria, tightness of the chest, hypotension, wheezing and anaphylaxis. The treatment required depends on the nature and severity of the adverse reaction. Suspicion of allergic or anaphylactic type reactions requires immediate discontinuation of the injection. In case of shock, standard medical treatment for shock should be implemented.
Patients in receipt of incompatible transfusion, who receive very large doses of anti-D immunoglobulin, should be monitored clinically and by biological parameters.
GAMMA anty-D 50 is made from human plasma in persons of high anti-D antibody titre. 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 measures taken are considered effective for enveloped viruses such as HIV, HBV and HCV. The measures taken may be of limited value against non-enveloped viruses such as HAV and/or parvovirus B19. There is reassuring clinical experience regarding the lack of hepatitis A or parvovirus B19 transmission with immunoglobulins and it is also assumed that the antibody content makes an important contribution to the viral safety.
It is strongly recommended that every time that GAMMA anty-D 50 is administered to a patient, the name and batch number of the product are recorded in order to maintain a link between the patient and the batch of the product.
4.5 Interactions with other medicinal products and other forms of interaction
Interactions of the GAMMA anty-D 50 product with other drugs were not studied. The information included in this point were obtained on the basis of written sources and current guidelines.
Active immunization with live virus vaccines (e.g. measles, mumps, rubella, varicella) should be postponed for 3 months after the administration of anti-D immunoglobulin, because anti-D immunoglobulin may weaken the efficacy of live virus vaccines. 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 the use of anti-D immunoglobulin a temporary increase in passively transmitted antibodies may occur, leading to false-positive results of serologic tests for the presence of antibodies, e.g. Coombs’ test in newborn babies.
4.6 Fertility, pregnancy and lactation
The product GAMMA anty-D 50 is used during pregnancy.
The product GAMMA anty-D 50 is used during breastfeeding.
No animal fertility studies have been conducted with GAMMA anty-D 50. Clinical experience with human anti-D immunoglobulin suggests that no harmful effects on fertility are to be expected.
4.7 Effects on ability to drive and use machines
GAMMA anty-D 50 has no influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and low back pain may occur occasionally.
Rarely human immunoglobulins may cause a sudden fall in blood pressure and, in isolated cases, anaphylactic shock, even when the patient has shown no hypersensitivity to previous administration.
Injection site reaction: swelling, erythema, induration, warmth, pruritus, bruising, rash
Tabulated list of adverse reactions
The table below was prepared in accordance with the MedDRA System Organ Classes classification (System Organ Classes and recommended terminology).
The frequency has been determined according to the following criteria: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to 1/1,000), very rare (<1/10,000), not known (cannot be estimated from the available data)
|MedDRA System Organ Classes||Adverse reaction||Frequency|
|Immune system disorders||Hypersensitivity, anaphylactic shock|
(shortness of breath, symptoms of shock)
|very rare (including single cases)|
|Nervous system disorders||Headache||rare|
|Cardiac disorders||Tachycardia||very rare (including single cases)|
|Gastrointestinal disorders||Nausea, vomiting|
|Skin and subcutaneous tissue disorders||Skin reaction||rare|
|Erythema, pruritus||not known|
|Musculoskeletal and connective tissue disorders||Arthralgia||not known|
|General disorders and administration site conditions||Fever, malaise, chills||not known|
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Pharmacovigilance Department of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products: Al. Jerozolimskie 181C, 02-222 Warsaw, phone number: + 48 22 49-21-301, fax: + 48 22 49-21-309, e-mail: firstname.lastname@example.org.
Adverse reactions can also be reported to the Marketing Authorisation Holder.
See section 4.4 for safety information with reference to infectious agents.
There is no data concerning overdosage of the product GAMMA anty-D 50.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunity serums and immunoglobulins,
ATC code: J06BB01
GAMMA anty-D 50 includes specific antibodies (IgG) against antigen D (Rh) of human erythrocytes. During pregnancy, and especially at the time of childbirth, fetal red blood cells may enter the maternal circulation. When the woman is Rh(D)-negative and the fetus Rh(D)-positive, the woman may become immunised to the Rh(D) antigen and produce anti-Rh(D) antibodies which cross the placenta and may cause haemolytic disease of the newborn.
Passive immunisation with anti-D immunoglobulin prevents Rh(D) immunisation in more than 99% of cases provided that a sufficient dose of anti-D immunoglobulin is administered soon enough after exposure to Rh(D)-positive fetal red blood cells.
The product’s dose protects about 2,5 ml of positive blood cells from the immunising effect. The product administered intramuscularly in a woman up to 72 hours after miscarriage prevents her from the creation of anti-D antibodies, thus preventing from haemolytic disease of newborns in her next pregnancy.
The mechanism by which anti-D immunoglobulin suppresses immunisation to Rh(D)- positive red cells is not known. Suppression may be related to the clearance of the red cells from the circulation before they reach immunocompetent sites or, it may be due to more complex mechanisms involving recognition of foreign antigen and antigen presentation by the appropriate cells at the appropriate sites in the presence or absence of antibody.
5.2 Pharmacokinetic properties
After intramuscular administration, the detectable titre of antibodies can be observed after about 4 hours.
The titre usually occurs after up to 5 days.
The half-life period in the recipient’s circulation with a normal IgG level is 2 weeks. This half-life may vary from patient to patient.
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
5.3 Preclinical safety data
Laboratory animal tests (on guinea pigs and white mice) showed that GAMMA anty-D 50 is not toxic.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Water for injections
The product must not be mixed with other medicinal products.
6.3 Shelf life
6.4 Special precautions for storage
Storage in a refrigerator (2°C – 8°C).
Ampoules should be stored in the outer packaging in order to be protected from light.
6.5 Nature and contents of container
1 ml of the solution in a type I glass ampoule – 1 per package
6.6 Special precautions for disposal and other handling
The product should be administered intramuscularly by a physician or nurse. The product should be brought to room or body temperature before use. You should make sure that the solution in the ampoule is transparent or slightly opalising. Do not use solutions that are cloudy or have deposits. Any unused product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
„BIOMED-LUBLIN” Wytwórnia Surowic i Szczepionek Spółka Akcyjna
20-029 Lublin, ul. Uniwersytecka 10
Phone 81 533 82 21
fax 81 533 80 60
8. MARKETING AUTHORISATION NUMBER(S)
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 10 January 1989
Date of latest renewal: 21 August 2014
10. DATE OF REVISION OF THE TEXT