RHESONATIV Solution for injection Ref.[49912] Active ingredients: Anti-D (rh) immunoglobulin

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administrated product should be clearly recorded.

Ensure that Rhesonativ is not administered into a blood vessel, because of the risk of shock. Injections have to be given intramuscularly, and care should be taken to draw back on the plunger of the syringe before injection in order to be certain that the needle is not in a blood vessel. In the case of postnatal use, the product is intended for maternal administration. It should not be given to the new-born infant. The product is neither intended for use in Rh(D) positive individuals nor for individuals already immunised to Rh(D) antigen. Patients should be observed for at least 20 minutes after administration and for at least 1 hour after an accidental intravenous injection.

Hypersensitivity

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.

Rhesonativ 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 Rhesonativ 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 in receipt of incompatible transfusion, who receive very large doses of anti-D immunoglobulin, 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 for Rhesonativ, 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 higher doses of Rhesonativ are prescribed.

Patients should be informed about first symptoms of thromboembolic events including shortness of breath, pain and swelling of a limb, focal neurological deficits and chest pain and should be advised to contact their 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, for example the antiglobulin test (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.

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 virus 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 Rhesonativ 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.

Important information about some of the ingredients of Rhesonativ

This medicine contains less than 1 mmol sodium (23 mg) per 1 mL (625 IU), that is to say essentially ‘sodium-free’.

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, then the efficacy of such a vaccination may be impaired.

Pregnancy

This medicinal product is intended for use in pregnancy.

Breastfeeding

This medicinal product can be used during breastfeeding. Immunoglobulins are excreted in human milk. No study drug-related adverse events were reported in children delivered of more than 450 women who received postpartum administration of Rhesonativ.

Fertility

No animal fertility studies have been conducted with Rhesonativ. Clinical experience with human anti-D immunoglobulin suggests that no harmful effects on fertility are to be expected.

Rhesonativ has no influence on the ability to drive and use machines.

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 administration.

Local reactions at injection sites: swelling, soreness, redness, induration, local heat, itching, bruising, local pain, tenderness and rash, some of these reactions can be prevented by dividing larger doses over several injection sites.

For safety with respect to transmissible agents, see 4.4.

There are no robust data on the frequency of adverse reactions from clinical trials. The following adverse reactions have been reported:

The table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level). 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).

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 listed in Appendix V.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.