RHOPHYLAC Solution for injection Ref.[6195] Active ingredients: Anti-D (rh) immunoglobulin

In the case of postpartum use, anti-D immunoglobulin 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.

Hypersensitivity

Allergic reactions to anti-D immunoglobulin may occur even in patients who have tolerated previous administrations. 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 treatment of shock should be observed. If symptoms of allergic or anaphylactic type reactions occur, immediate discontinuation of the administration is required.

The concentration of IgA in Rhophylac was found to be below the detection limit of 5 micrograms/ml. Nevertheless, the product may contain trace amounts of IgA. Although anti-D immunoglobulin has been used successfully to treat selected IgA-deficient patients, individuals who are deficient in IgA have the potential for developing IgA antibodies and may have anaphylactic reactions after administration of blood components containing IgA. The physician must therefore weigh the benefit of treatment with Rhophylac against the potential risks of hypersensitivity reactions.

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.

Obesity

There have been reports that the intramuscular administration of Rhophylac in patients with a body mass index (BMI) ≥ 30 is associated with an increased risk of lack of efficacy. Therefore, in patients with a BMI ≥30, intravenous administration should be considered.

Excipients

Rhophylac contains less than 1 mmol sodium (23 mg) per syringe, that is to say essentially “sodium-free”.

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). They may be of limited value against non-enveloped viruses such as hepatitis A (HAV) and 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 Rhophylac 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.

Live attenuated virus vaccines

Active immunisation with live virus vaccines (e.g. measles, mumps, rubella or varicella) should be postponed until 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 to 4 weeks of a live virus vaccination, then the efficacy of such a vaccination may be impaired.

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. blood group A or B, Rh (C), Rh (D) may interfere with some serological tests for RBC antibodies, for example the antiglobulin test (Coombs' test) particularly in Rh(D) positive neonates whose mothers have received antepartum prophylaxis.

Fertility

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

Pregnancy

This medicinal product is intended for use in pregnancy.

No study drug-related adverse events were reported in children delivered of 432 women who received antepartum administration of Rhophylac 300 micrograms.

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 256 women who received postpartum administration of Rhophylac 300 micrograms, nor in children delivered of 139 women who received postpartum administration of Rhophylac 200 micrograms.

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

Summary of the safety profile

The most serious adverse reactions observed during the treatment are hypersensitivity or allergic reactions which may in rare cases progress to a sudden fall in blood pressure and anaphylactic shock even when the patient has shown no hypersensitivity to previous administration. When anti-D immunoglobulins are administered by the intramuscular route, local pain and tenderness may be observed at the injection site.

Tabulated list of adverse reactions

The following adverse reactions have been reported from 592 patients in clinical studies and from post-marketing experience. The summary table presented below is according to the MedDRA system organ classification (SOC and Preferred Term Level).

Frequency has been evaluated using the following criteria: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000).

There have been spontaneous reports of severe intravascular haemolysis when anti-D has been administered intravenously to Rh(D) positive patients with primary immune thrombocytopenia (ITP). Haemolysis resulting in death has been reported. The exact frequency of this adverse event is not known.

For safety information with respect to transmissible agents, see section 4.4.

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 UK Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App store.

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