Rhesogam^® N (Solution) Instructions for Use

Marketing Authorization Holder

CSL Behring, AG (Switzerland)

ATC Code

J06BB01 (Human anti-Rho(D) immunoglobulin)

Active Substance

Human anti-D immunoglobulin (Ph.Eur. European Pharmacopoeia)

Dosage Form

Rhesogam® N

Solution for intravenous and intramuscular administration 750 IU/1 ml: syringe 2 ml with needle included

Dosage Form, Packaging, and Composition

Solution for intravenous and intramuscular administration colorless or with a yellowish tint, transparent or slightly opalescent.

Excipients: human albumin, glycine, sodium acetate, sodium chloride, acetic acid, water for injections.

The drug contains no more than 30 mg/1 ml of human plasma proteins, of which 10 mg/1 ml is human albumin (stabilizer), not less than 95% of other proteins are IgG immunoglobulins; IgA content not more than 5 mcg/ml.

2 ml – syringes of colorless glass (1) in a set with a needle (1 pc.) – blisters (1) – cardboard packs.

Clinical-Pharmacological Group

Drug for the prevention of Rh-conflict. Specific immunoglobulin

Pharmacotherapeutic Group

Immunoglobulin

Pharmacological Action

It contains specific antibodies of the IgG class against the Rhesus antigens Rh₀(D) of human erythrocytes. During pregnancy and, especially, during childbirth, fetal erythrocytes can enter the mother’s bloodstream.

If the woman is Rh-negative and the fetus is Rh-positive, the woman can be immunized with the Rhesus antigen, resulting in the production of anti-Rhesus antibodies, which pass through the placental barrier and can cause hemolytic disease of the newborn.

Passive immunization with human anti-Rhesus immunoglobulin prevents Rhesus immunization in more than 99% of cases, provided that a sufficient dose of anti-Rhesus immunoglobulin is administered in a timely manner, before exposure to Rh-positive fetal erythrocytes begins.

The mechanism by which human anti-Rhesus immunoglobulin suppresses immunization to Rh-positive erythrocytes is unknown.

Suppression may be associated with the removal of erythrocytes from the bloodstream before they reach immunocompetent sites, or more complex mechanisms may exist involving the recognition of foreign antigens and antigen presentation by appropriate cells on appropriate structures in the presence or absence of antibody.

Pharmacokinetics

Measurable antibody levels can be obtained approximately 4 hours after intramuscular administration.

C_max in serum is usually reached after 5 days.

After intravenous administration, measurable antibody levels are determined immediately after injection.

The T_1/2 of human anti-Rhesus immunoglobulin is 3-4 weeks.

T_1/2 is characterized by interindividual variability.

The average T_1/2 from the bloodstream in pregnant women with normal IgG levels was 17 days.

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

Indications

Prevention of Rh-positive immunization of Rh-negative women not sensitized to the Rho(D) antigen: antenatal prophylaxis; antenatal prophylaxis of pregnancy complications: abortion or threatened abortion, ectopic pregnancy or hydatidiform mole; intrauterine fetal death, transplacental transfusion as a result of antenatal bleeding, amniocentesis, chorionic villus sampling, obstetric manipulations, for example, external cephalic version, invasive intervention, cordocentesis, abdominal trauma or therapeutic intrauterine intervention; postpartum prophylaxis.

Treatment of Rh-negative patients after transfusion of incompatible Rh-positive blood or other drugs containing erythrocytes.

ICD codes

Dosage Regimen

Administer intravenously slowly or intramuscularly. In case of hemorrhagic disorders, when intramuscular injections are contraindicated, this agent should be administered intravenously. A single dose is 200-300 mcg (1000-1500 IU). The regimen and frequency of administration depend on the indications and clinical situation.

When treating Rh-negative patients after transfusion of incompatible Rh-positive blood or other drugs containing erythrocytes, the required dose should be determined by a transfusion specialist.

Adverse Reactions

Immune system disorders rarely – hypersensitivity, anaphylactic shock.

Nervous system disorders infrequently – headache.

Cardiac and vascular disorders rarely – tachycardia, arterial hypotension.

Respiratory, thoracic and mediastinal disorders rarely – dyspnea.

Gastrointestinal disorders rarely – nausea, vomiting.

Skin and subcutaneous tissue disorders infrequently – skin reactions, erythema, pruritus.

Musculoskeletal and connective tissue disorders rarely – arthralgia.

General disorders: rarely – edema, pain, erythema, induration.

Local reactions rarely – feeling of heat, itching, rash.

Contraindications

Hypersensitivity to the active substance; hypersensitivity to human immunoglobulins; intramuscular route of administration is contraindicated in persons with severe thrombocytopenia or other coagulation disorders; Rh-negative postpartum women sensitized to the Rh₀(D) antigen, in whose serum Rh antibodies are detected; newborns.

Use in Pregnancy and Lactation

Used during pregnancy and breastfeeding according to indications.
Immunoglobulins are excreted in milk.

Pediatric Use

Contraindicated for use in newborns.

Special Precautions

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

Necessary therapeutic measures depend on the nature and severity of the adverse effect.

In case of shock development, standard medical anti-shock therapy should be carried out.

In case of postpartum use, human anti-Rhesus immunoglobulin is intended for administration to the mother.

Human anti-Rhesus Rh₀(D) immunoglobulin is not intended for administration to Rh-positive patients or patients already immunized to the Rh₀(D) antigen.

Patients should be observed for at least 20 minutes after administration of this immunoglobulin.

The concentration of IgA in the Rhesogam* N preparation was found to be below the detectable value of 5 mcg/ml.

Nevertheless, this preparation may contain trace amounts of IgA.

Although human anti-Rhesus immunoglobulin has been successfully used in the treatment of patients with selective IgA deficiency, individuals with IgA deficiency may produce antibodies to IgA and experience anaphylactic reactions to the administration of blood components containing IgA.

Therefore, the physician should assess the benefit of prescribing Rhesogam^® N and the risk of possible hypersensitivity reactions.

Since Rhesogam^® N contains 11.5 mg (0.5 mmol) of sodium chloride in each syringe, this information should be taken into account for patients on a controlled sodium diet.

Safety information regarding infectious agents

When using drugs obtained from human blood or plasma, the possibility of transmission of infectious agents cannot be completely excluded.

Drug Interactions

Should not be mixed with other drugs, as interaction with other drugs has not been studied.

Active immunization with live virus vaccines (e.g., measles, rubella, mumps, or varicella vaccines) should be postponed for 3 months after the last administration of human anti-Rhesus immunoglobulin, as the effectiveness of live virus vaccines may be reduced.

If it is necessary to administer human anti-Rhesus immunoglobulin within 2-4 weeks after administration of a live virus vaccine, the effectiveness of such vaccination may be insufficient.

After an immunoglobulin injection, a transient increase in passively transferred antibodies in the patients’ blood may lead to false-positive results in serological testing for antibodies against erythrocytes, for example, in the Coombs test in newborns.

This immunoglobulin may contain antibodies to other Rhesus antigens, for example, anti-Rh(C), which may be detected by sensitive serological methods after administration of the drug.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.