Immunorho

The solution is clear and colourless or pale-yellow or light brown. During storage it may present a slight opalescence or a small amount of particles in suspension.
Each 2 ml pre-filled syringe contains 1500* IU human anti-D immunoglobulin.
*100 micrograms of human anti-D immunoglobulin correspond to 500 International Units (IU).
1 ml of solution for injection in pre-filled syringe contain: See Table 1.

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The potency is determined using the European Pharmacopoeia assay. The equivalence in International Units of the International Reference Preparation is stated by the World Health Organization.
Distribution of IgG subclasses (approximate values): IgG₁ 66.0%; IgG₂ 30.0%; IgG₃ 2.5%; IgG₄ 1.5%.
The maximum content of IgA is 300 micrograms/ml.
Produced from the plasma of human donors.
Excipient with known effect: This product contains up to a maximum of 7.8 mg sodium per 2 ml pre-filled syringe.
Excipients/Inactive Ingredients: Solution for injection in pre-filled syringe: Glycine, Sodium chloride, Water for injections.

Pharmacotherapeutic group: Immune sera and immunoglobulins, immunoglobulins, specific immunoglobulins: Anti-D (Rh) immunoglobulin. ATC code: J06BB01.
Pharmacology: Pharmacodynamics: Anti-D immunoglobulin contains specific antibodies (IgG) against the D (Rh) antigen 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 mechanism by which anti-D immunoglobulin suppresses immunisation to Rh(D) positive red cell 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.
Paediatric population: No specific studies of efficacy and safety are available on paediatric population.
Pharmacokinetics: Human anti-D immunoglobulins for intramuscular administration is slowly absorbed into the recipient's circulation and reaches a maximum after a delay of 2-3 days.
Human anti-D immunoglobulin has a half-life of about 3-4 weeks. This half-life may vary from patient to patient.
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
Paediatric population: No specific studies of efficacy and safety are available on paediatric population.
Toxicology: Preclinical safety data: Immunoglobulins are normal constituents of the human body.
In animals single dose toxicity testing is of no relevance since higher doses result in overloading. Repeated dose toxicity testing and embryo-fetal toxicity studies are not practicable due to the induction of and interference with antibodies. Effects of the product on the immune system of the newborn have not been studied.
Since clinical experience provides no hint for carcinogenic and mutagenic effects of immunoglobulins, experimental studies, particularly in heterologous species, are not considered necessary.

Prevention of Rhesus sensitization, Rhesus induced morbus haemolyticus neonatorum in Rh(-) pregnancy which pregnant with Rh(+) husband.

Posology: The dose of anti-D immunoglobulin should be determined according to the level of exposure to Rh(D) positive red blood cells and considering that 0.5 ml of packed Rh(D) positive red blood cells or 1 ml of Rh(D) positive blood is neutralised by approximately 10 micrograms (50 IU) of anti-D immunoglobulin.
Consideration should also be given to dose and dose schedule for human anti-D immunoglobulin for intramuscular use recommended in other official or Member States guidance.
Prevention of Rhesus sensitization, Rhesus induced morbus haemolyticus neonatorum in Rh(-) pregnancy which pregnant with Rh(+) husband: Antenatal prophylaxis: According to general recommendations, currently administered doses range from 50-330 micrograms or 250-1650 IU.
Planned antenatal prophylaxis: A single dose at 28-30 weeks of gestation or two doses at 28 and 34 weeks.
Antenatal prophylaxis following complications of pregnancy: A single dose should be administered as soon as possible and within 72 hours and if necessary repeated at 6-12 week intervals throughout the pregnancy.
Postnatal prophylaxis: According to general recommendations, currently administered doses range from 100 to 300 micrograms or 500 to 1500 IU. If the lower dose (100 micrograms or 500 IU) is administered, a test should be performed to determine the extent of fetal-maternal haemorrhage.
For postnatal use, the product should be administered to the mother as soon as possible within 72 hours of delivery of an Rh positive (D, D^weak, D^partial) infant. If more than 72 hours have elapsed, the product should not be withheld but administered as soon as possible.
The postnatal dose must still be given even when antenatal prophylaxis has been administered and even if residual activity from antenatal prophylaxis can be demonstrated in maternal serum.
If a large feto-maternal haemorrhage [>4 mL (0.7%-0.8% of women)] is suspected, e.g. in the event of fetal/neonatal anaemia or intrauterine fetal death, its extent should be determined by a suitable method e.g. Kleihauer-Betke acid elution test to detect fetal HbF (fetal hemoglobin) or flow cytometry which specifically identifies Rh(D) positive cells. Additional doses of anti-D immunoglobulin should be administered accordingly (10 micrograms or 50 IU per 0.5 ml fetal red blood cells).
The use of an alternative intravenous product is recommended as it allows to achieve adequate plasma levels immediately. If no intravenous product is available, a very high dose should be administered intramuscularly for a period of several days (see Precautions).
Paediatric population: The safety and efficacy of IMMUNORHO in children have not been established. The appropriate dosage should be calculated with the advice of a specialist in transfusion medicine.
Method of administration: Intramuscular use: If a large volume (>2 ml for children or >5 ml for adults) is required, it is recommended to administer the medicine in divided doses at different sites.
If intramuscular administration is contraindicated (bleeding disorders), an alternative intravenous product should be used.
Overweight patients: In case of overweight/obese patients the use of an intravenous anti-D product must be considered (see Precautions).
For instruction before administration, see Special precautions for disposal and handling under Cautions for Usage.

Consequences of an overdose are not known.

Hypersensitivity to the active substance or to any of the excipients listed in Description.
Hypersensitivity to human immunoglobulins, especially in patients with antibodies against IgA.

Ensure that IMMUNORHO is not administered into a blood vessel, because of the risk of shock.
In case of postnatal use, the product is intended for maternal administration. It should not be given to the new-born infant.
Traceability: In order to improve the traceability of biological medicinal products, the name and batch number of the administered product should be clearly recorded.
Hypersensitivity: True hypersensitivity reactions are rare, but allergic type responses to anti-D immunoglobulin may occur.
IMMUNORHO 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 anti-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 IMMUNORHO against the potential risks 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.
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.
Haemolytic reactions: Patients receiving very high doses of anti-D immunoglobulin due to incompatible transfusion, should be monitored clinically and by biological parameters because of the risk of haemolytic reaction.
Thromboembolism: Arterial and venous thromboembolic events including myocardial infarction, stroke, deep venous thrombosis and pulmonary embolism have been associated with the use of immunoglobulins. Although thromboembolic events have not been observed in patients receiving IMMUNORHO, those patients should be sufficiently hydrated before use of immunoglobulins.
Caution should be exercised in patients with preexisting risk factors for thrombotic events (such as hypertension, diabetes mellitus and a history of vascular disease or thrombotic episodes, patients with acquired or inherited thrombophilic disorders, patients with prolonged periods of immobilization, severely hypovolemic patients, patients with diseases which increase blood viscosity), especially when high doses of IMMUNORHO are prescribed.
Patients should be informed about first symptoms of thromboembolic events including dyspnea, pain and swelling of a limb, focal neurological deficits and chest pain, and should be advised to contact the physician immediately upon onset of symptoms.
Interference with serological testing: 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.
Passive transmission of antibodies to erythrocyte antigens, e.g. A, B, D may interfere with some serological tests for red cell antibodies (e.g. Coombs' test) particularly in Rh(D) positive neonates whose mothers have received antenatal prophylaxis.
Overweight/obese patients: In overweight/obese patients, due to the possible lack of efficacy in case of intramuscular administration, an intravenous anti-D product is recommended.
Information on safety with respect to transmissible agents: 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 human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) and for the non-enveloped hepatitis A virus (HAV).
The measures taken may be of limited value against non-enveloped viruses such as 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 IMMUNORHO 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.
Warnings on excipients: This medicinal product contains up to 7.8 mg sodium per 2 ml prefilled syringe, equivalent to 0.38% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
Effects on ability to drive and use machines: IMMUNORHO has no influence on the ability to drive and use machines.
Use in Children: No specific measures or monitoring are required for the paediatric population.

Pregnancy: This medicinal product is intended for use in pregnancy.
Breast-feeding: This medicinal product can be used during breast-feeding. Immunoglobulins are excreted in human milk.
Fertility: No studies have been conducted on fertility with IMMUNORHO. Clinical experience with human anti-D immunoglobulin suggests that no harmful effects on fertility are to be expected.

Summary of the safety profile: Adverse reactions such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, low blood pressure and moderate 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 administrations.
Local reactions at infusion site: swelling, soreness, redness, induration, local heat, itching, bruising and rash.
Tabulated list of adverse reactions: The table as follows has been drawn up according to the MedDRA system organ classification (SOC and Preferred Term Level). The table reports undesirable effects associated with the use of human anti-D immunoglobulin for intramuscular use.
There are no robust data on the frequency of adverse reactions derived from clinical trials.
Frequencies have been evaluated according to the following convention: 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). (See Table 2.)

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Paediatric population: No specific data are available on paediatric population.
For safety with respect to transmissible agents, see Precautions.
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation 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 national reporting system.

Live attenuated virus vaccines: Active immunisation with live virus vaccines (e.g. measles, mumps or rubella) should be postponed for 3 months after the last 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, the efficacy of such a vaccination may be impaired.
Paediatric population: Although specific interaction studies have not been performed in the paediatric population, no difference between adults and children is to be expected.

Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Special precautions for disposal and handling: Solution for injection: The product should be brought to room or body temperature before use.
The solution is clear and colourless or pale-yellow or light brown. Do not use solutions that are cloudy or have deposits.
Screw in the plunger shaft of the pre-filled syringe and inject.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

Solution for injection: Store in a refrigerator (2°C-8°C). Do not freeze.
Keep in the original container and in the outer carton in order to protect from light.
Shelf life: 3 years.

Vaccines, Antisera & Immunologicals

J06BB01 - anti-D (rh) immunoglobulin ; Belongs to the class of specific immunoglobulins. Used in passive immunizations.

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