Rezogam H - instructions for use, dose, side effects, contraindications

	in 1 ml	in 2 ml (in a filled syringe)
Active substance:
Human immunoglobulin antiresus	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	q.s. to pH = 5.2	q.s. to pH = 5.2
Water for injections	q.s. up to 1 ml	q.s. up to 2 ml

Rezogam ® H contains no more than 30 mg / ml of human plasma proteins, of which 10 mg / ml human albumin (stabilizer), at least 95% of other proteins are immunoglobulins IgG; content IgA not more than 5 μg / ml.

Description:

Colorless or with a yellowish tinge, a clear or slightly opalescent solution.

Pharmacotherapeutic group:MIBP - globulin

ATX: & nbsp

J.06.B.B.01 Immunoglobulin human antiresus Rho (D)

Pharmacodynamics:

Rezogam ® H contains specific antibodies of class IgG against Rhesus antigens Rho(D) of human erythrocytes.During pregnancy and, especially during childbirth, the red blood cells of the fetus can enter the bloodstream of the mother. If the woman is Rh-negative, and the fetus is Rh-positive, a woman can be immunized with Rh-antigen, as a result of which antirezus antibodies are produced that pass through the placenta and can cause a hemolytic disease of the newborn. Passive immunization with human immunoglobulin antiresus prevented Rh-immunization in more than 99% of cases provided that a sufficient dose of immunoglobulin antiresus is administered in advance before the onset of Rh-positive fetal red blood cells.

The mechanism by which an immunoglobulin antiresus inhibits immunization to Rh-positive red blood cells is unknown. Suppression can be associated with excretion of erythrocytes 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 an antibody.

Pharmacokinetics:

Measurable antibody levels can be obtained approximately 4 hours after intramuscular administration. The maximum concentration in serum is usually achieved after 5 days. After intravenous administration, measurable antibody levels are determined immediately after injection.

The half-life of human immunoglobulin antiresus is 3-4 weeks. The half-life may vary from patient to patient. Mean half-life of the bloodstream in pregnant women with normal levels IgG was 17 days.

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

Indications:

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

- prenatal prophylaxis;

- prenatal prophylaxis of complications of pregnancy: abortion or threatening abortion, ectopic pregnancy or bladder arthritis; intrauterine fetal death, transplacental transfusion as a result of prenatal bleeding, amniocentesis, chorion biopsy, obstetric manipulations, for example, external obstetric turn, invasive intervention,Cordocentesis, abdominal trauma or therapeutic intrauterine intervention;

- postpartum prophylaxis.

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

Contraindications:

- Hypersensitivity to the active substance or any other component included in the preparation;

- increased sensitivity to human immunoglobulins;

- intramuscular route of administration is contraindicated in individuals with severe thrombocytopenia or other hemostatic disorders;

- Rh-negative puerperas sensitized to the antigen Rho(D), in the serum of which Rh-antibody was detected;

- newborns.

Pregnancy and lactation:

Pregnancy

Rezogam® H can be used in pregnancy.

There were no reported side effects associated with the use of the drug in children born to mothers who received Rezogam ® H in the prenatal period.

Breastfeeding period

Rezogam ® H can be used during breastfeeding. Immunoglobulins are excreted with milk.There were no reported side effects associated with the use of the drug in children born to mothers who received Rezogam® H in the postpartum period.

Dosing and Administration:

Doses of human immunoglobulin antiresus determined on the basis of the degree of action of Rh-positive red blood cells and the position that 0.5 ml of Rh-positive red blood cells or 1 ml of Rh-positive blood are neutralized approximately 10 μg (50 ME) human immunoglobulin antiresus. Based on clinical studies of Rezogam® H, the following dosing regimens are recommended, however, when using this drug in each individual country, local guidelines for medical personnel on the use of an immunoglobulin antiresus for intravenous and intramuscular injection should be used.

Prevention of Rh-positive immunization of Rh-negative women not sensitized to the antigen Rho(D)

- antenatal prevention: It is recommended that a single dose of 300 μg (1500 ME) intravenously or intramuscularly at the end of the 28th to the 30th week of pregnancy;

- Preventing complications of pregnancy: a single dose of 300 mcg is necessary as soon as possible and no later than 72 hours after the complication is detected. If necessary, subsequent administration of Rezogam® H at intervals of 12 weeks is allowed throughout the gestation period;

- postpartum prevention: for intravenous administration, a dose of 200 μg (1000 ME). If the drug is administered intramuscularly, it is recommended to administer it at a dose of 200 mcg (1000 ME) to 300 μg (1500 ME);

For postnatal prophylaxis, Rezogam® H should be administered as early as possible within the first 72 hours after delivery. In case the drug failed to be administered within the first 72 hours after delivery, the drug should still be administered after childbirth as soon as possible. Postnatal prophylaxis with the introduction of the drug should be carried out even if prenatal prophylaxis has been done and even if the residual serum levels of the drug are present from prenatal prophylaxis.

In case of suspected large amounts of blood from the fetus to the mother (more than 4 ml (found in 0.7-0.8% of women)), for example, in cases of fetal anemia or intrauterine fetal death, the volume should be determined by the most appropriate method, for example, using the Kleichauer-Betke test (Kleihauer- Betke) or by the method of flow cytometry, which allows to determine specifically Rho(D) positive erythrocytes, and additional doses of human immunoglobulin antiresus should be administered from the following calculation: 20 mcg (100 IU) per 1 ml of fetal erythrocytes.

Transfusion of incompatible blood or blood products

The recommended dose is 20 μg (100 ME) human immunoglobulin antiresus on 2 ml of transfused rhesus-positive blood or 1 ml of erythrocyte mass. The required dose should be determined by a blood transfusion specialist. Benchmarks for Rho(D) positive erythrocytes should be performed every 48 hours with further introduction of human immunoglobulin antiresus until complete elimination Rho(D) positive erythrocytes from the circulation. An intravenous route of administration is recommended, since it allows immediate attainment of the required concentration of human immunoglobulin concentration by anti-insus in the blood plasma. When intramuscular injection should be administered large doses of the drug for several days. If the volume of incompatible blood during transfusion was more than 300 ml, it is sufficient to introduce a maximum dose of human immunoglobulin antiresus equal to 3000 μg (15,000 ME).

Mode of application

Before use, Rezogam® H should be heated to room temperature or to body temperature. The solution should be clear or slightly opalescent. Do not use the solution in case of turbidity or precipitation.

Rezogam ® H can be administered intravenously slowly or intramuscularly. In the case of hemorrhagic disorders, when intramuscular injections are contraindicated, Rezogam® H should be administered intravenously. If intramuscularly large doses (> 5 mL) are required, it is recommended that they be administered in divided doses and at different locations.

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems (classification MedDRA) and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10,000 and <1/1 000), rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable reactions

Classification of undesirable reactions in accordance with the damage to organs and organ systems (MedDRA)	Clinical manifestations	Category frequencies occurrence
Impaired immune system disorders	Hypersensitivity, anaphylactic shock	Rarely
Disturbances from the nervous system	Headache	Infrequently
Heart Disease	Tachycardia	Rarely
Vascular disorders	Arterial hypotension	Rarely
Disturbances from the respiratory system, chest and mediastinal organs	Dyspnea	Rarely
Disorders from the gastrointestinal tract	Nausea, vomiting	Rarely
Disturbances from the skin and subcutaneous tissues	Skin reactions, erythema, pruritus	Infrequently
Disturbances from the musculoskeletal and connective tissues	Arthralgia	Rarely
General disorders and disorders at the site of administration	Fever, discomfort, chills	Infrequently
	In the place of administration: edema, pain, erythema, denseness, sensation of heat, itching, rash	Rarely

Overdose:

Data on drug overdose are absent. Patients who received very high doses of human immunoglobulin antiresus after transfusion of incompatible blood components should be observed by clinical and biochemical indicators due to the risk of developing a hemolytic reaction. In other cases, an overdose in Rhesus negative patients should not lead to more frequent or more severe side effects than those observed with conventional doses.

Interaction:

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

Live attenuated viral vaccines

It should postpone active immunization with live viral vaccines (eg, measles, rubella, mumps, or chickenpox vaccines) for three months after the last injection of human immunoglobulin, since the effectiveness of live viral vaccines is possible. If there is a need for the administration of human immunoglobulin antiresus in a period of 2 to 4 weeks after the introduction of live viral vaccine, the effectiveness of such vaccination may not be sufficient.

After the injection of an immunoglobulin, a transient increase in passively transferred antibodies in the blood of patients can lead to false positive results when serological testing of antibodies against erythrocytes is carried out, for example, when the Coombs sample is placed in neonates.

Rezogam ® H may contain antibodies to other Rh antigens, for example, anti-Rh(C), which can be determined by sensitive serological methods after administration of the drug.

Special instructions:

In the case of postpartum use, the human immunoglobulin antiresus is intended for the administration of the mother.

This preparation is not intended for administration to Rh-positive patients or patients already immunized with Rho(D) antigen.

Patients should be monitored for at least 20 minutes after drug administration.

When developing an allergic or anaphylactic reaction, it is necessary to stop the drug immediately.

There may be allergic reactions to the introduction of human immunoglobulin antiresus. Patients should be informed of early signs of hypersensitivity reactions, including urticaria, generalized urticaria, shortness of breath, wheezing, arterial hypotension and anaphylaxis. The necessary treatment depends on the nature and severity of the side effect. In the case of shock, standard medical anti-shock therapy should be used.

It was found that the concentration IgA in the preparation Rezogam ® H is below the determined value of 5 μg / ml. However, this preparation may contain trace amounts IgA. Although human immunoglobulin antiresus is successfully used in the treatment of patients with selective IgA deficiency, IgA-deficient individuals can develop antibodies to IgA and cause anaphylactic reactions to the administration of blood components containing IgA. Therefore, the physician should evaluate the benefits of prescribing Rezogam® H and the risk of possible hypersensitivity reactions.

Safety information for infectious agents

Standard measures to prevent the transmission of infections due to the use of drugs derived from human blood or plasma include selection of donors, screening of individual donations and plasma pools for the presence of specific infection markers, and the inclusion of effective production steps aimed at inactivating and / or removing viruses. Despite this, with the use of drugs derived from human blood or plasma, the possibility of transmitting infectious agents can not be completely ruled out. This provision also applies to unknown or new viruses and other infectious agents. The measures taken are considered effective against enveloped viruses, such as HIV, hepatitis B and C viruses.They can be partially effective against non-enveloped viruses, such as the hepatitis A virus and parvovirus B 19.

There is an encouraging clinical experience showing the absence of cases of transmission of hepatitis A viruses or parvovirus B 19 with immunoglobulins, it is also assumed that the antibodies contained in the preparation make an important contribution to improving antiviral safety.

It is strongly recommended that each time the Rezogam® H preparation is administered to the patient, write down the name and serial number of the drug in order to maintain the connection between the patient and the drug series.

Rezogam ® H can not be mixed with other medicinal products, since interaction with other drugs has not been studied.

The drug is intended for single use (one syringe - one patient). The unused product or its residues should be disposed of in accordance with the requirements in force.

Do not use the drug after the expiry date indicated on the syringe label and the cardboard pack.

Effect on the ability to drive transp. cf. and fur:

The effects of the preparation Rezogam ® H on the ability to drive a vehicle or moving mechanisms have not been noted.

Form release / dosage:

Solution for intravenous and intramuscular administration, 750 ME (150 μg) / ml.

Packaging:

2 ml each (1500 ME human immunoglobulin antiresus Rho(D)) in a transparent colorless glass syringe (Type I, Hebrew F.), sealed with a stopper and a plastic cap with control of the first autopsy.

1 syringe and a needle in a PVC blister / paper.

For 1 blister with instructions for use in a cardboard bundle.

Storage conditions:

Store at a temperature of 2 to 8 ° C in a dark place.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002781

Date of registration:19.12.2014

Date of cancellation:2019-12-19

The owner of the registration certificate:CESEL Behring AGCESEL Behring AG Switzerland

Manufacturer: & nbsp

CSL BEHRING, AG Switzerland

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp13.10.2015

Illustrated instructions

Instructions

Rezogam® H (RHESOGAM® N)