Immunoro Kedrion (Lyophilisate) Instructions for Use

Marketing Authorization Holder

Kedrion S.p.A. (Italy)

Contact Information

KEDRION S.p.A. (Italy)

ATC Code

J06BB01 (Human anti-Rho(D) immunoglobulin)

Active Substance

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

Dosage Form

Immunoro Kedrion

Lyophilisate for preparation of solution for intramuscular injection 300 mcg (1500 IU): fl. 1 pc. incl. with solvent

Dosage Form, Packaging, and Composition

Lyophilisate for preparation of solution for intramuscular injection white or light yellow in color; solvent – transparent colorless liquid; prepared solution is opalescent colorless or light yellow in color.

Excipients: glycine, sodium chloride.

Solvent: water for injections (up to 1 ml).

Glass vials (1) in a set with solvent (amp. 2 ml 1 pc.) – cardboard packs.

Clinical-Pharmacological Group

Drug for the prevention of Rh-conflict. Specific immunoglobulin

Pharmacotherapeutic Group

Immunoglobulin

Pharmacological Action

Immunoglobulin. The active component of the drug is specific antibodies against the Rh₀(D) antigen of human erythrocytes. The drug prevents isoimmunization in the Rh-negative body of a woman, resulting from the entry of fetal blood into the mother’s bloodstream during the birth of an Rh-positive child, during spontaneous and artificial abortions, in the case of amniocentesis, or in the event of trauma to the abdominal organs during pregnancy.

Anti-D immunoglobulins are polyclonal immunoglobulins, the mechanism of action of which is to neutralize Rh₀(D) antigens present in the Rh-positive blood of the embryo. The period of effective action of the drug averages from 48 to 144 hours, with the maximum concentration of human anti-Rhesus Rh₀(D) immunoglobulin reached on average 56 hours after administration of the drug.

The drug is an immunologically active protein fraction isolated from virus-inactivated human plasma, tested for the absence of antibodies to human immunodeficiency viruses (HIV-1, HIV-2), hepatitis C virus, and hepatitis B surface antigen.

Pharmacokinetics

A detectable concentration of antibodies is achieved in the blood approximately 20 minutes after intramuscular injection of the drug. C_max of antibodies in blood plasma is usually reached 2-3 days after injection.

T_1/2 of human anti-Rhesus Rh₀(D) immunoglobulin is individual, equal to that of normal human immunoglobulin, and is 3-4 weeks. Immunoglobulin and its complexes are destroyed in the cells of the reticuloendothelial system.

Indications

• Prevention of anti-D (Rh₀) immunization in Rh-negative women (Rh₀(D)), not sensitized to the Rh₀(D) antigen, and in women with weakly positive Rhesus blood (Du), during pregnancy and the birth of an Rh-positive child. The drug is used for artificial and spontaneous termination of pregnancy in Rh-negative women, not sensitized to the Rh₀(D) antigen, in the case of Rh-positive blood of the father, as well as during amniocentesis, external cephalic version, trauma to the abdominal organs, antenatal bleeding, ectopic pregnancy, and chorionic villus sampling;
• Prevention of anti-D (Rh₀) immunization in Rh-negative patients after incompatible transfusion of Rh-positive blood or erythrocyte concentrates.

ICD codes

Dosage Regimen

The drug solution is administered intramuscularly.

Postpartum prophylaxis. 1000-1500 IU (200-300 mcg) is recommended as the optimal standard dose without prior testing for fetal hemoglobin (HbF) infiltration into the maternal bloodstream using the Kleihauer-Betke method. The drug is administered to the mother as soon as possible after delivery, but no later than 72 hours.

Antenatal and postpartum prophylaxis. First dose of 1000-1500 IU (200-300 mcg) at the 28th week of pregnancy. The next dose of 1000-1500 IU (200 – 300 mcg) is administered within 72 hours after delivery, if the child is born Rh-positive.

After termination of pregnancy, ectopic pregnancy, or hydatidiform mole. Within the first 72 hours after the intervention, the drug is administered at a dose of 600-750 IU (120-150 mcg) up to the 12th week of pregnancy; 1250-1500 IU (250-300 mcg) after 12 weeks of pregnancy; 1250-1500 IU (250-300 mcg) after amniocentesis or chorionic villus sampling.

After incompatible transfusion of Rh-positive blood. 500 IU-1250 IU (100-250 mcg) for every 10 ml of transfused blood over several days.

In case of coagulation system pathology, when intramuscular administration of drugs is contraindicated, human anti-Rhesus Rh₀(D) immunoglobulin can be administered subcutaneously. After the injection, a compress is carefully applied to the injection site.

If a larger total dose (more than 5 ml) is required, it is recommended to divide it into smaller doses and administer injections at different sites.

Preparation and administration of the drug solution

The vial with the drug lyophilisate and the ampoule with the solvent should be warmed to room temperature or body temperature. Draw the contents of the ampoule with the solvent into an injection syringe, remove the protective cap from the rubber stopper of the vial with the lyophilisate and slowly introduce the solvent into the vial; gently shake the vial with the solution or let it stand until the lyophilisate is completely dissolved; draw the solution into the syringe; change the needle and perform the injection.

Incomplete dissolution of the lyophilisate leads to loss of drug activity. Do not use if the solution is cloudy or contains sediment. The lyophilisate from the opened vial must be reconstituted and used immediately. Remains of the drug must be destroyed.

Adverse Reactions

Local reactions: pain at the injection site. This can be avoided by administering a large volume of solution in several doses of less than 5 ml at several different sites.

Systemic reactions: infrequently – fever, skin reactions, chills; rarely – dyspeptic phenomena (nausea and vomiting), decreased blood pressure, tachycardia, allergic or anaphylactic reactions.

Contraindications

• Hypersensitivity to the components of the drug;
• Rh-positive and Rh-negative women sensitized to the Rh₀(D) antigen, in whose blood serum Rh antibodies are detected;
• Newborns.

Use in Pregnancy and Lactation

This medicinal product is used during pregnancy and within 72 hours after delivery. No harmful effects on the course of pregnancy, the fetus or the newborn have been noted.

Special Precautions

The drug must not be administered intravenously due to the possibility of shock development. Administration must be intramuscular. To avoid the drug entering blood vessels, before starting the administration, pull back the syringe plunger and check if there is blood in the syringe. True allergic reactions to intramuscularly administered human anti-Rhesus Rh₀(D) immunoglobulin are rare. At the first signs of anaphylactoid reactions, anti-shock therapy with antihistamines, alpha-adrenergic agonists, and corticosteroids is carried out.

Intolerance to immunoglobulins develops in very rare cases of immunoglobulin A (IgA) deficiency, when the patient has antibodies against IgA.

Observation of the patient continues for 30-60 minutes after the injection. Administration of the drug is immediately stopped if an allergic or anaphylactic reaction is suspected. In case of shock development, anti-shock therapy is applied.

After immunoglobulin administration, a passive increase in the antibody content in the patient’s blood may be observed, which may lead to erroneous false-positive interpretation of serological test results. The administration of human anti-Rhesus Rh₀(D) immunoglobulin significantly affects the results of such studies as antibody determination and blood grouping, including the Coombs test and the antiglobulin test.

Viral safety. In the manufacture of medicinal products from human blood or plasma, a set of measures is applied to prevent possible transmission of infection to patients. These measures include careful selection of healthy donors, guaranteeing the exclusion of the risk of infectious contamination of donors, as well as control of each donor’s blood and the total plasma pool for the absence of viruses and infections. Each unit of plasma used for the manufacture of the drug is tested for the absence of hepatitis B surface antigen and antibodies to human immunodeficiency viruses (HIV-1, 2), and to hepatitis C virus. Each plasma pool is also controlled for the absence of hepatitis C virus RNA by polymerase chain reaction. Only plasma that gives negative results for all the above tests is used for the manufacture of the drug. The production of human blood products also includes stages of production processing of human blood or plasma that allow for the inactivation or removal of viruses. Despite this, when using medicinal products made from human blood or plasma, the possibility of transmitting infection, including unknown or new viruses and other infectious agents, cannot be completely excluded.

Overdose

No cases of overdose have been reported.

Drug Interactions

Human anti-Rhesus Rh₀(D) immunoglobulin must not be mixed with other drugs.

It reduces the activity of attenuated live vaccines against measles, rubella, mumps, and varicella for a period of up to 3 months.

Storage Conditions

The drug should be stored out of the reach of children and protected from light at a temperature not exceeding 25°C (77°F). Do not freeze.

Shelf Life

Shelf life – 3 years.

Dispensing Status

The drug is dispensed by prescription.

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.