Resogam H, 1500 me (300 mcg)/2ml 2 ml syringes with needle

Pharmacotherapeutic group

MIBP-globulin

ATC code

J06BB01

Pharmacodynamics:

Rezogam® H contains IgG class specific antibodies against the Rho(D) rhesus antigen of human red blood cells. During pregnancy and especially during childbirth fetal red blood cells can enter the mother’s bloodstream. If the woman is Rh-negative and the fetus is Rh-positive the woman may be immunized with the Rh antigen resulting in the production of anti-Rh antibodies that pass through the placenta and can cause hemolytic disease in the newborn. Passive immunization with human anti-Rhesus immunoglobulin prevents Rh immunization in more than 99% of cases if a sufficient dose of anti-Rhesus immunoglobulin is administered in advance of exposure to Rh-positive fetal red blood cells.

The mechanism by which human anti-Rhesus immunoglobulin suppresses immunization to Rhesus-positive red blood cells is unknown. The suppression may be due to the removal of red blood cells from the bloodstream before they reach immunocompetent sites or there may be more complex mechanisms involving recognition of foreign antigens and presentation of antigens by appropriate cells on appropriate structures in the presence or absence of the antibody.

Pharmacokinetics:

A measurable antibody content can be obtained approximately 4 hours after intramuscular administration. Maximum serum concentrations are usually reached after 5 days. After intravenous injection, measurable antibody values are determined immediately after injection.

The elimination half-life of human anti-Rhesus immunoglobulin is 3-4 weeks. The half-life can vary from patient to patient. The average half-life from the circulation in pregnant women with normal IgG levels was 17 days.

IgG and complexes with IgG are degraded in cells of the reticuloendothelial system.

Indications

Prevention of rhesus-positive immunization of rhesus-negative women who are not sensitized to the Rho(D) antigen:

Prenatal prophylaxis;

Prenatal prevention of pregnancy complications: abortion or threatened abortion ectopic pregnancy or bubblegum; intrauterine fetal death transplacental transfusion due to prenatal bleeding amniocentesis chorionic biopsy obstetric manipulation such as external obstetric rotation invasive cordocentesis abdominal trauma or therapeutic intrauterine intervention;

Postnatal prevention.

The treatment of Rh-negative patients after transfusions of Rh-positive incompatible blood or other drugs containing red blood cells.

Active ingredient

Composition

in 1 ml

in 2 ml

(in a filled syringe)

The active ingredient:

Human anti-Rhesus immunoglobulin

750 ME

1500 ME

Rho(D)

(150 µg)

(300 µg)

Excipients:

Human albumin

10 mg

20 mg

Glycine

20.6 mg

41.2 mg

Sodium chloride

≤0.250 mmol

≤0.500 mmol

Acetic acid

qs. to pH=5.2

q.s. To pH=5.2

Water for injection

qs. up to 1 ml

q.s. up to 2 ml

Resogam® H contains no more than 30 mg/ml human plasma proteins, of which 10 mg/ml human albumin (stabilizer), at least 95% of other proteins are IgG immunoglobulins; IgA content no more than 5 µg/ml.

How to take, the dosage

Doses of Human Anti-Rhesus Immunoglobulin are based on the exposure rate of Rh-positive red blood cells and the position that approximately 10 mcg (50 ME) of Human Anti-Rhesus Immunoglobulin is neutralized by 05 ml of Rh-positive red blood cells or 1 ml of Rh-positive blood. Based on the clinical trials of Rezogam® H, the following dosing schedules are recommended; however, for the use of this drug in any given country, local guidelines for medical professionals on the use of intravenous and intramuscular human anti-Rhesus immunoglobulin should be consulted.

Prenatal prophylaxis of rhesus-positive immunization in rhesus-negative women who are not sensitized to the Rho(D) antigen

Prenatal prophylaxis: a single dose of 300 mcg (1500 ME) intravenously or intramuscularly between the 28th and 30th weeks of pregnancy is recommended;

– prevention of pregnancy complications: a single dose of 300 mcg should be administered as soon as possible and no later than 72 hours after a complication is identified. If necessary, subsequent administration of Resogam® H at 12-week intervals during the whole period of pregnancy is allowed;

Postpartum prophylaxis: for intravenous administration a dose of 200 mcg (1000 ME) is sufficient. If the drug is administered intramuscularly, a dose of 200 mcg (1000 ME) to 300 mcg (1500 ME) is recommended;

In postpartum prophylaxis, Resogam® H should be administered as soon as possible within the first 72 hours after delivery. If the drug cannot be administered within the first 72 hours after delivery, the drug should still be administered as soon as possible after delivery. Postpartum prophylaxis with administration should be given even if prenatal prophylaxis has been given and even if there is residual activity of the drug from prenatal prophylaxis in the mother’s serum.

. If there is suspicion of a significant blood volume from the fetus to the mother (greater than 4 ml (occurs in 07-08% of women)), e.g. in case of fetal anemia or fetal death, the volume should be determined by the most appropriate method e.g. Kleihauer-Betke test or by flow cytometry for specific identification of Rho(D) positive red blood cells and additional doses of human antiresus immune globulin should be administered as follows: 20 µg (100 ME) per 1 ml of fetal erythrocytes.

Transfusion of incompatible blood or blood products

The recommended dose is 20 mcg (100 ME) of human antiresus immunoglobulin per 2 mL of rhesus-positive blood transfused or per mL of red blood cell mass. The required dose must be determined by the transfusion specialist. Control tests for Rho(D) positive red blood cells should be performed every 48 hours with further administration of human anti-Rhesus immunoglobulin until complete elimination of Rho(D) positive red blood cells from the circulation. The intravenous route of administration is recommended because it allows immediate attainment of the desired plasma concentration of human anti-Rhesus immunoglobulin. When administered intramuscularly, large doses should be given over several days. If the volume of incompatible blood in a transfusion is greater than 300 ml, a maximum dose of anti-Rhesus Human Immunoglobulin of 3000 mcg (15000 ME) is sufficient.

How to use

Heated to room temperature or body temperature before using Rezogam® H. The solution should be clear or slightly opalescent. Do not use if the solution is cloudy or has precipitated.

Resogam® H may be administered slowly intravenously or intramuscularly. In case of hemorrhagic disorders when intramuscular injection is contraindicated, Rezogam® H should be administered intravenously. If large doses (> 5 ml) are required intramuscularly, it is recommended to administer them fractionally and in different locations.

Interaction

Interaction with other drugs has not been studied. The information presented in this section is derived from the literature and current guidelines.

Live attenuated viral vaccines

Active immunization with live viral vaccines (e.g., measles-mumps-mumps or varicella vaccines) should be delayed for three months after the last administration of human antiresus immunoglobulin because the effectiveness of live viral vaccines may decrease. If it becomes necessary to administer human anti-Rhesus immunoglobulin 2 to 4 weeks after administration of the live virus vaccine, the effectiveness of this vaccination may not be sufficient.

After immunoglobulin injection, a transient increase of passively transferred antibodies in the blood of patients may lead to false-positive results in serological tests for antibodies against red blood cells, such as the Coombs test in newborns.

Resogam® H may contain antibodies to other Rh antigens such as anti-Rh(C) which may be detected by sensitive serological methods after infusion.

Special Instructions

In the case of postnatal use, human anti-Rhesus immunoglobulin is intended to be administered to the mother.

The present product is not intended to be administered to rhesus-positive patients or patients already immunized against the Rho(D) antigen.

Patients must be observed for a minimum of 20 minutes after administration.

If an allergic or anaphylactic reaction develops, the drug administration must be stopped immediately.

An allergic reaction to administration of human anti-Rhesus immunoglobulin may occur. Patients should be made aware of the early signs of hypersensitivity reactions including urticaria generalized urticaria difficulty breathing wheezing arterial hypotension and anaphylaxis. The necessary therapeutic measures depend on the nature and severity of the side effect. If shock develops, standard drug antishock therapy should be given.

The concentration of IgA in Rezogam® H has been found to be below the detectable value of 5 µg/ml. Nevertheless, this product may contain trace amounts of IgA. Although Human Anti-Rhesus Immunoglobulin has been successfully used to treat patients with selective IgA deficiency, IgA-deficient individuals may develop antibodies to IgA and have anaphylactic reactions when given blood components containing IgA. Therefore a physician should evaluate the benefit of administration of Rezogam® H and the risk of possible hypersensitivity reactions.

Safety Information Regarding Infectious Agents

Standard measures to prevent transmission of infections due to the use of human blood or plasma products include donor selection testing individual donations and plasma pools for specific markers of infection and incorporating effective manufacturing steps to inactivate and/or remove viruses. Nevertheless, when using preparations derived from human blood or plasma, the possibility of transmission of infectious agents cannot be completely excluded. This also applies to unknown or new viruses and other infectious agents. The measures taken are considered effective against coated viruses such as HIV, hepatitis B and C viruses. They may be partially effective against viruses without coatings, such as hepatitis A and parvovirus B 19.

There is encouraging clinical experience showing no transmissions of hepatitis A or parvovirus B 19 with immunoglobulins and the antibodies in the product are thought to make an important contribution to antiviral safety.

It is highly recommended that each time Rezogam® H is administered to a patient, the name and series number of the drug be recorded in order to maintain the link between the patient and the series of drugs.

Resogam® H should not be mixed with other medications because interactions with other medications have not been studied.

The drug is intended for single use (one syringe, one patient). Unused drug or its residues must be disposed of in accordance with applicable requirements.

Do not use the product after the expiration date listed on the syringe label and carton packet.

There is no known effect of Rezogam® N on the ability to drive or operate moving machinery.

Synopsis

Contraindications

– hypersensitivity to the active ingredient or any other component of the drug;

– hypersensitivity to human immunoglobulins;

– The intramuscular route of administration is contraindicated in persons with severe thrombocytopenia or other disorders of hemostasis;

– Rh-negative women who have sensitized to the Rho(D) antigen in the serum of whom Rh antibodies are found;

– Newborns.

Side effects

The adverse reactions presented below are listed according to organ and system damage (MedDRA classification) and frequency of occurrence. The frequency is defined as follows: very common (≥1/10) common (≥1/100 and <1/10) infrequent (≥1/1000 and <1/100) rare (≥1/10 000 and <1/1 000) very rare (<1/10 000 including individual cases). Frequency categories were formed based on clinical studies of the drug and post-registration follow-up.

Frequency of adverse reactions

Classification of adverse reactions according to organ and organ system involvement (MedDRA)

Clinical manifestations

Category

frequency

occurrence

Immune system disorders

Hypersensitivity anaphylactic shock

Overdose

Pregnancy use

Pregnancy

Resogam® N can be used in pregnancy.

There have been no reported adverse effects associated with the use of the drug in children born to mothers who received Rezogam® N during the antenatal period.

Breast-feeding period

Resogam® H can be used during breast-feeding. The immunoglobulins are excreted with milk. No adverse effects have been reported in infants born to mothers who received Rezogam® H during the postpartum period.