Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: CSL Behring GmbH, Emil-von-Behring-Strasse 76, 35041, Marburg, Germany
Pharmacotherapeutic group: immune sera and immunoglobulins: Anti-D (Rh) immunoglobulin
ATC Code: J06BB01
Rhophylac contains specific antibodies (IgG) against the Rh(D) antigen of human erythrocytes. It can also contain antibodies to other Rh antigens, e.g. anti-Rh C antibodies.
During pregnancy, and especially at the time of childbirth, foetal RBCs may enter the maternal circulation. When the woman is Rh(D) negative and the foetus 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 new-born.
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 foetal RBCs.
The mechanism by which anti-D immunoglobulin suppresses immunisation to Rh(D) positive RBCs is not known. Suppression may be related to the clearance of the RBCs 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.
In Rh(D) negative healthy male volunteers, both the intravenous and intramuscular administration of 200 micrograms (1000 IU) of Rhophylac at 48 hours after injection of 5 ml of Rh(D) positive RBCs resulted in an almost complete clearance of Rh(D) positive RBCs within 24 hours.
While the intravenous administration of Rhophylac caused an instant onset of Rh(D) positive RBC disappearance, the onset of elimination of Rh(D) positive RBCs following intramuscular administration was delayed as anti-D IgG had to be first absorbed from the injection site.
On an average, 70% of injected Rh(D) positive RBCs were cleared 2 hours after intravenous administration of Rhophylac.
After intramuscular administration, a similar degree of Rh(D) positive RBC clearance was measured after 12 hours.
Furthermore, the efficacy, safety and pharmacokinetics of Rhophylac are supported by the results of three clinical studies in pregnant women.
In one clinical study, Rhophylac 200 micrograms (1000 IU) was administered postpartum in 139 per protocol subjects.
In the other two clinical studies, Rhophylac 300 micrograms (1500 IU) was administered antepartum in 408 per protocol subjects and in addition postpartum in 256 subjects who gave birth to a Rh(D) positive baby.
None of the pregnant women included in these studies developed antibodies against the Rh(D) antigen.
In the clinical studies with Rhophylac 300, 207 per protocol subjects were given the antepartum dose of Rhophylac 300 intravenously and 201 per protocol subjects were given it intramuscularly. In more than 99 % of cases, the method of post- and antepartum administration was the same.
Clinical studies with Rhophylac at doses below 200 micrograms (1000 IU) have not been conducted.
The safety and efficacy of Rhophylac have not been established in clinical studies in paediatric subjects after incompatible transfusion of Rh(D) positive blood or other products containing Rh(D) positive RBCs.
The bioavailability of human anti-D immunoglobulin for intravenous use is complete and immediate. IgG is quickly distributed between plasma and extravascular fluid.
Human anti-D immunoglobulin for intramuscular administration is slowly absorbed into the recipient’s circulation and reaches a maximum after a delay of 2 to 3 days.
Human anti-D immunoglobulin has a half-life of about 3 to 4 weeks. This half-life may vary individually from patient to patient.
IgG and IgG-complexes are broken down in cells of the reticuloendothelial system.
Due to induction of and interference with antibodies, there are limited preclinical data of relevance for anti-D immunoglobulin.
Repeated dose testing and embryo-foetal toxicity studies have not been conducted and are impracticable to conduct.
The potential for mutagenic effects of immunoglobulins have not been studied.
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