SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
GAMMA anty-D 150, 150 micrograms/ml
Solution for injection
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 ml of the solution consists of:
Human anti-D immunoglobulin 150 micrograms (750 IU)
Human protein content not less than 90 mg
Each ampoule contains 150 micrograms (750 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
Pregnancy / birth of an Rh(D)-positive child
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.
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.
The product is administered intramuscularly within 48 hours, up to 72 hours at the latest in the following conditions:
– 1 dose (150 μg) is used after physiological delivery, 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,
– 2 doses (300 μg) are used after pathological delivery, e.g.: caesarean section, manual extraction of the placenta, after delivery of stillborn foetus,
– 2-3 doses (300-450 μg) are used after fetomaternal haemorrhage (it is recommended to establish the extent of transplacental leakage and choose appropriate dosing),
– after multiple delivery the number of doses equals the number of babies.
II. The product is administered intramuscularly in the 28th week of pregnancy:
– 2 one-time doses (300 μg) in Rh negative women in the 28th week of pregnancy, who have no anti-D antibodies detected with the papain and antiglobulin tests.
Method of administration
The GAMMA anty-D 150 should be administered via the intramuscular route.
In the case of coagulation disorders, when intramuscular administration is contraindicated, GAMMA anty-D 150 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 150 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 150 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 150 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 150 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 150 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 150 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 150 is used during pregnancy.
The product GAMMA anty-D 150 is used during breastfeeding.
No animal fertility studies have been conducted with GAMMA anty-D 150. Clinical experience with human anti-D immunoglobulin suggest that no harmful effects on fertility are to be expected.
4.7 Effects on ability to drive and use machines
GAMMA anty-D 150 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 reactions||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|
|At injection site: swelling, pain, tenderness, erythema, induration, warmth, pruritus, rash|
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 email@example.com. 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 150.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Immunity serums and immunoglobulins,
ATC code: J06BB01
GAMMA anty-D 150 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. If the mother’s blood group is Rh- minus and the foetus’ is Rh- positive, the mother may become allergic to the Rh(D) antigen and produce anti-Rh(D) antibodies, which in turn permeate the placenta and may cause haemolytic disease in newborn babies.
Passive immunity to anti-D immunoglobulins prevents immunisation of Rh(D) in over 99% of cases, on condition that a sufficient dose of anti-D immunoglobulin is administered early enough after the exposition to Rh(D)- positive erythrocytes of the foetus.
The product’s dose protects about 7 ml of positive blood cells from the immunising effect. The product administered intramuscularly in a woman up to 72 hours after delivery or miscarriage prevents her from the creation of anti-D antibodies, thus preventing from haemolytic disease of newborns in her next pregnancy.
The mechanism of anti-D immunoglobulin by stopping the immunisation of Rh(D)- positive erythrocytes is unknown. The stopping effect may be connected with release of erythrocytes from the circulation before they reach an immunocompetent position or it can be connected with the mechanism of immunologic complex creation pertaining to the recognition of an alien antigen and its presentation by appropriate cells in a proper place with or without the presence of an 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. A given half-life period may differ in each patient.
IgG antibodies and complexes of IgG antibodies are destroyed in the cells of the reticular-endothelial system.
5.3 Preclinical safety data
Laboratory animal tests (on guinea pigs and white mice) showed that GAMMA anty-D 150 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. Before use the product should be brought to room or body temperature. 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
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 19 November 1986
Date of latest renewal: 21 August 2014
10. DATE OF REVISION OF THE TEXT