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

Pharmacotherapeutic group: immune sera and immunoglobulins, immunoglobulins, specific immunoglobulins: - anti-D (Rh) immunoglobulin
ATC code: J06BB01

Anti-D immunoglobulin contains specific antibodies (IgG) against the D (Rh) antigen of human erythrocytes.

During pregnancy, and especially at the time of childbirth, foetal 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 cells 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.

Studies in Patients with Postpartum Prophylaxis (Study 1-6) and in Patients with Antenatal Prophylaxis (Study 7)

Clinical trials with Rhesonativ were initiated with the aim to evaluate the efficacy and safety of the product. The following table provides an overview on the most important findings in terms of efficacy:

PPP: postpartum prophylaxis; ANP: antenatal prophylaxis; n.r.: not reported
^* 6-8 weeks before expected date of delivery.
From these studies it can be reasonably concluded that treatment with Rhesonativ provides effective anti–D prophylaxis.

Study in Transfusion of Rh–incompatible blood components

Study 8 assessed the efficacy of Rhesonativ in 21 Rh–negative volunteers who were injected with Rh–positive, ABO-compatible fetal red cells in amounts corresponding to 10 mL cord blood (1 case), 25 mL (10 cases) and 50 mL (10 cases). Two to 3 days later 260 micrograms of Rhesonativ were given intramuscularly. Six months (in 1 case 9 months) after the start of the experiment no serologic evidence for Rh–immunization was found in any individual. Six months to 2.5 years later, 8 subjects of the 25 mL group and all 10 subjects of the 50 mL group received 5 mL Rh–positive, ABO-compatible cord blood. After 2 to 3 days, 260 respectively 333 micrograms Rhesonativ were injected. After another 6 months (in 1 case after 8 months) no Rh–antibodies were detected in any subject.

From these experimental findings it was concluded that Rh–prophylaxis is achieved with 10 micrograms of anti–D immunoglobulin per mL of fetal blood. It was concluded that, as far as Rh–immunization due to fetomaternal haemorrhage at the end of the pregnancy is concerned, a dose of 260 micrograms Rhesonativ prevents serologically detectable Rh–immunisation in at least 998 Rh–negative mothers out of a thousand.

Pharmacokinetic Study with Rhesonativ

The basic pharmacokinetics and turnover of Rhesonativ were investigated in fifteen Rh– negative pregnant women who were given Rhesonativ intramuscularly at 28 weeks' gestation. The doses were 125 micrograms in 8 and 250 micrograms in 7 of the women. In addition three non-pregnant Rh–negative women were given the smaller dose. The biological half life of anti-D IgG after an intramuscular injection of 125 microgram in these women was in line with what could be expected from the literature (see section 5.2).