Gabriglobin-IgG - instructions for use, dose, side effects, contraindications

It is a highly purified preparation of immunoglobulin G, isolated from blood plasma obtained from no less than 1000 healthy donors, individually tested for the absence of antibodies to HIV-1, HIV-2, to hepatitis C virus and the surface antigen of the hepatitis B virus. The drug contains antibodies of class IgG. present in a normal population, has low anticomplementary activity. The active principle is immunoglobulins, mainly of the class G (IgG), possessing the activity of antibodies of different specificity. In the preparation the content of specific antibodies is normalized: to a cytomegalovirus - not less than 1: 800; to herpes simplex virus - not less than 1: 3200; to the influenza virus - at least 1:80.

Distribution of subclasses IgG approximately corresponds to their distribution in the native blood plasma of man. The optimal dose of the drug can restore a low concentration IgG up to normal values.

The mechanism of action when applied according to the indications, with the exception of substitution therapy, is not fully explained, but includes the immunomodulating effect.

The drug increases the nonspecific resistance of the body.

In the production process the preparation is not subjected to chemical or enzymatic treatment, does not contain preservatives and antibiotics.

Pharmacokinetics:

After intravenous administration, the drug is distributed relatively quickly between plasma and extravascular fluid. Equilibrium between intravascular and extravascular parts is achieved in 3-5 days. The half-life of the drug from the body in patients with primary immunodeficiency can vary and is usually 3-5 weeks. Complexes IgG are destroyed in the cells of the reticulo-endothelial system.

Indications:

1) Substitution therapy with primary immunodeficiencies (FID) with impaired antibody production:

- Congenital agammaglobulinemia and hypogammaglobulinemia;

- general variable immune deficiency;

- severe combined immune deficiency;

- Wiskott-Aldrich syndrome.

2) Substitution therapy for secondary immunodeficiencies:

- multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective vaccination with pneumococcal vaccine;

- chronic lymphoid leukemia with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective prophylactic antibacterial therapy;

- congenital syndrome of acquired human immunodeficiency (AIDS) in children in the presence of recurrent infections;

- hypogammaglobulinemia in patients after allogeneic transplantation of hematopoietic stem cells;

- severe forms of bacterial and viral infections; postoperative complications accompanied by bacteremia; generalized infections (sepsis).

3) As an immunomodulating agent:

- with idiopathic thrombocytopenic purpura (ITP) in children or adults with a high risk of bleeding or before surgery to correct the number of platelets;

- with Guillain-Barre syndrome;

- with Kawasaki disease;

- with other autoimmune diseases (systemic lupus erythematosus, vasculitis);

- with hives.

Contraindications:

Contraindications for the use of the drug are:

- hypersensitivity to the active substance or any other component included in the formulation;

- increased sensitivity to homologous immunoglobulins, especially in very rare cases of immunoglobulin deficiency A (IgA), when the patient has antibodies to IgA.

In cases of severe sepsis only contraindication for use is anaphylactic shock on human blood products in history.

Carefully:

Pregnancy, lactation, renal failure in history, diabetes mellitus, hypovolemia, obesity, concomitant therapy with nephrotoxic drugs, advanced age (over 65 years), increased plasma viscosity (hypergammaglobulinemia, hyperfibrinogenemia, sickle-cell anemia).

Pregnancy and lactation:

The safety of using human normal immunoglobulin during pregnancy and lactation has not been studied in controlled clinical trials,so their appointment to pregnant women and women during breastfeeding should be done with caution.

The experience of the clinical use of immunoglobulin allows us to conclude that there is no adverse effect on the course of pregnancy, on the fetus or on the child during breastfeeding.

Dosing and Administration:

Before administration, the preparation is warmed to room temperature or body temperature. The drug should be administered only in the form of intravenous infusions, initially at a rate of 0.5 mg / kg body weight (15-20 drops per minute or 0.75-1 ml / min) in the first 10-15 minutes, then at a speed of 30- 40 drops per minute (1.5-2 ml / min). In case of good tolerability, the infusion rate can be gradually increased to 8 mg / kg body weight / min (about 10 ml / min). In patients with primary immunodeficiencies who tolerated substitution therapy with the drug, the infusion rate can be gradually increased to a maximum of 12 mg / kg body weight / min.

The dose and dosage regimen depend on the indication for use. In the case of substitution therapy, the dose of the drug can be selected individually for each patient, depending on the pharmacokinetic parameters and the clinical response.As a guide, the following doses of the drug are recommended.

Substitution therapy for primary immunodeficiencies

It is recommended to choose a dosing regimen in which the concentration IgG increases a minimum of 5-6 g / l (definition of the content IgG spend before further infusion). Equilibrium concentrations are achieved 3-6 months after the start of treatment. The recommended starting dose is from 0.4 to 0.8 g / kg of body weight, the subsequent dose is not less than 0.2 g / kg of body weight every 3-4 weeks. Doses of the preparation necessary to achieve concentration IgG 5-6 g / l, are from 0.2 to 0.8 g / kg body weight per month. The interval between doses, when equilibrium concentrations are reached, varies from 3 to 4 weeks. Measure concentrations IgG to regulate the dose and the interval of administration.

Replacement therapy for multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective vaccination with pneumococcal vaccine; with chronic lymphoid leukemia with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective prophylactic antibacterial therapy; with congenital AIDS in children in the presence of recurrent infections

A dosage regimen of 0.2 to 0.4 g / kg body weight is recommended every 3-4 weeks.

Substitution therapy for hypogammaglobulinemia in patients after allogeneic transplantation of hematopoietic stem cells

Doses of the drug necessary to maintain concentration IgG at a level of more than 5 g / l, range from 0.2 to 0.4 g / kg body weight every 3-4 weeks.

Heavy forms of bacterial and viral infections, postoperative complications, accompanied by bacteremia; generalized infections (sepsis)

For the treatment of infectious diseases and postoperative complications, it is recommended to apply the drug in a dose of 0.2-0.8 g / kg body weight daily for 3-7 days. With the development of sepsis, the drug is prescribed as soon as possible after diagnosis of the syndrome in the starting dose to 1-2 g / kg of body weight, depending on the patient's condition, then - 0.2-0.8 g / kg body weight for 3-5 days.

Idiopathic thrombocytopenic purpura

In case of an exacerbation, appoint 0.8 to 1 g / kg of body weight on the first day (it is possible to repeat this dose again one more time in the next 3 days) or 0.4 g / kg of body weight daily for 2-5 days. In case of relapse, treatment can be repeated.

Guillain-Barre Syndrome

0.4 g / kg body weight for 5 days.There is limited experience in children.

Kawasaki disease

From 1.6 to 2 g / kg body weight in separate equal doses for 2-5 days or a single dose of 2 g / kg body weight once. Patients should be assigned acetylsalicylic acid as concomitant therapy.

Systemic lupus erythematosus, vasculitis

From 0.2 to 0.4 g / kg body weight daily for 3-10 days.

Hives

From 0.03 to 0.04 g / kg body weight daily for 4 days.

Special patient groups

According to clinical studies, patients with PID and ITP did not need a dosage adjustment for children.

Recommendations for dosage regimens are given in the table

Indications	Doses	Interval between injections
Substitution therapy
Primary immunodeficiencies	Starting dose: 0,4-0,8 g / kg of body weight, further: 0.2-0.8 g / kg body weight	Once, every 3-4 weeks until the concentration is reached IgG not less than 5-6 g / l.
Secondary immunodeficiencies	0,2-0,4 g / kg of weight	Once, every 3-4 weeks until the concentration is reached IgG not less than 5-6 g / l.
Prevention and treatment of children infected with human immunodeficiency virus	0.2-0.4 g / kg body weight	Once, every 3-4 weeks.
Hypogammaglobulinemia in patients after allogeneic transplantation of hematopoietic stem cells	From 0.2 to 0.4 g / kg body weight	Once, every 3-4 weeks
Heavy forms of bacterial and viral infections, postoperative complications	0.2-0.8 g / kg body weight	Daily for 3-7 days
Generalized infection (sepsis)	Starting dose: up to 1-2 g / kg body weight, further: 0.2-0.8 g / kg body weight	First day. Next: daily for 3-5 days
Immunomodulatory therapy
Idiopathic thrombocytopenic purpura	0,8-1,0 g / kg body weight or: 0.4 g / kg body weight	First day. It is possible to repeat a single administration in the next 3 days from the date of the first administration. Daily for 2-5 days
Guillain-Barre Syndrome	0.4 g / kg body weight	Daily for 5-7 days
Kawasaki disease	1.6-2 g / kg body weight or: 2 g / kg body weight	Assign in equal doses for 2-5 days in combination with the appointment acetylsalicylic acid. Once in combination with acetylsalicylic acid.
Systemic lupus erythematosus, vasculitis	0.2-0.4 g / kg body weight	Daily for 3-10 days
Hives	0,03-0,04 g / kg body weight	Daily for 4 days.

Side effects:

Undesirable reactions according to numerous clinical studies for intravenous immunoglobulin preparations, presented below, are listed in accordance with organ and organ damage and frequency of occurrence.Frequency of occurrence is defined as follows: very often (> 1/10), often (> 1/100 and <1/10), infrequently (> 1/1000 and <1/100), rarely (> 1/10 000 and < 1/1000), very rarely (<1/10 000. including individual cases).

Immune system disorders: rarely - Anaphylactic reactions (including anaphylactic shock), angioedema, edema of the face.

Violations from the blood and lymphatic system: infrequently - Anemia, anisocytosis, leukopenia, hemolysis.

Impaired nervous system: very often - headache; infrequently - dizziness, discomfort in the head, drowsiness; rarely aseptic meningitis.

Heart Disease: infrequent - palpitations (palpitation).

Violation from the vessels: often - arterial hypertension; infrequently - arterial hypotension, hot flashes, peripheral vascular disorders: very rarely - thromboembolic complications.

Disturbances from the respiratory system, organs of the thorax and mediastinum: infrequent breathing difficulties, a feeling of restraint in the throat.

Disorders from the gastrointestinal tract: often - nausea; infrequently - diarrhea, epigastric pain.

Disorders from the liver and bile ducts: infrequently - Hyperbilirubinemia.

Disturbances from the skin and subcutaneous tissues: often - hives, rashes: infrequently - itching, night sweats.

Disturbances from the musculoskeletal and connective tissue: often - backache: infrequently - pain in the neck, pain in the extremities.

Disorders from the kidneys and urinary tract: infrequently - proteinuria.

General disorders and disorders at the site of administration: often - chills, fatigue, fever, asthenia, influenza-like condition; infrequently - chest pain, general malaise, fever, pain at the injection site.

Laboratory and instrumental data: infrequent increase in the concentration of bound and unbound bilirubin in the blood, a positive direct Coombs test, a positive indirect Coombs test, an increase in lactate dehydrogenase activity in the blood, a decrease in hematocrit, an increase in the activity of aspartate aminotransferase, an increase in the concentration of blood creatinine, a decrease in blood pressure, an increase in blood pressure, , decreased hemoglobin.

Overdose:

Overdose can lead to hypervolemia and increased blood viscosity, especially in patients who are at risk, including elderly patients and patients with impaired renal function.

Interaction:

The drug is not recommended to dilute with various saline solutions. The use of immunoglobulin can disrupt the formation of immunity during vaccination with weakened live viral vaccines against measles, rubella, mumps and varicella. In this regard, after the introduction of immunoglobulin vaccinations against these infections are carried out no earlier than 3 months. After vaccination against these infections, immunoglobulin preparations should be administered no earlier than 2 weeks; If immunoglobulin is required before this time, vaccination should be repeated. In the case of measles, a decrease in the effectiveness of the vaccine can last for 1 year. Therefore, in patients vaccinated against measles, it is necessary to control the level of antibodies.

Vaccinations against other infections can be carried out at any time before or after the administration of the immunoglobulin.

Immunoglobulin therapy can be combined with antibiotics, hormones, cytokines, bacteriophages.

Special instructions:

The drug should not be used after the expiration date.

The drug is intended for single use.After opening the vial, the consumer is responsible for the storage time and storage conditions. The solution does not contain preservatives. Partially used preparation is not subject to storage and use.

In case of turbidity of the infusion solution or the presence of mechanical inclusions in the solution, the drug is not to be used.

Places of infusion should be provided with anti-shock therapy. Unused product and consumables should be disposed of in a suitable way.

During the infusion of the drug should closely monitor the patient's condition.

Some unwanted reactions can be observed more often:

- in the case of a high rate of administration;

- in patients with hypogammaglobulinemia or agammaglobulinemia with insufficiency IgA or without insufficiency IgA;

- in patients who receive human immunoglobulin therapy for the first time, or in rare cases, when switching to another immunoglobulin preparation, or with a long break after a previous infusion.

Possible complications can be avoided by making sure that:

- the patient does not show hypersensitivity to the human immunoglobulin normal with slow administration of the drug (0.5 mg / kg body weight / min);

- During and after the infusion period, all symptoms that occur in patients are carefully monitored. In particular, patients who have not been treated with normal human immunoglobulins or who have been transferred from another immunoglobulin preparation for intravenous administration or for a long interval after a previous infusion should be monitored during the first infusion and within the first hour after the first infusion to identify potential undesirable phenomena. All other patients should be monitored for at least 30 minutes after using the drug.

In case of development of an undesirable phenomenon it is necessary to reduce the rate of administration or to stop the administration of the drug. The required treatment depends on the nature and severity of the undesirable phenomenon.

In the case of development of shock, it is necessary to use standard treatment of shock conditions.

All patients before starting the introduction of human immunoglobulin for intravenous administration require appropriatehydration.

Hypersensitivity

True hypersensitivity reactions are rare. They can occur in very rare cases with a deficit IgA with antibodies to IgA. Rarely normal human immunoglobulin may be the cause of a decrease in blood pressure with the development of an anaphylactoid reaction, even in patients who previously tolerated normal human immunoglobulin therapy.

Hemolytic anemia

Human immunoglobulin preparations for intravenous administration may contain antibodies against blood group antigens that can act as hemolysins and bind in vivo with erythrocytes, which can cause a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia can develop after therapy with human immunoglobulin preparations for intravenous administration resulting from increased erythrocyte sequestration. Individual cases of renal and / or renal failure or disseminated intravascular coagulation disorder associated with hemolysis have been reported.

The development of hemolysis is associated with the following risk factors: high doses, regardless of the administration in the form of a single dose or individual doses for several days; as well as blood groups A (II), B (III) and AB (IV) in conjunction with the concomitant presence of the inflammatory process. When treating patients with blood groups A (II), B (III) or AB (IV) with high doses of the drug according to indications other than PID, it is advisable to take extra care.

There are separate reports of hemolysis cases in patients with PID receiving substitution treatment. It is necessary to monitor the clinical signs and symptoms of hemolysis in patients receiving therapy with human immunoglobulin preparations for intravenous administration. If there are signs and / or symptoms of hemolysis during or after infusions of the immunoglobulin for intravenous administration, the treating physician should consider eliminating further treatment.

Syndrome of aseptic meningitis (CAM)

When treating immunoglobulin preparations for intravenous administration, cases of the development of aseptic meningitis syndrome were recorded. After the abolition of the immunoglobulin for intravenous administration, the remission of CAM occurred within a few days without any consequences.Typically, this syndrome begins in the period from a few hours to 2 days after treatment with an immunoglobulin for intravenous administration.

When analyzing the cerebrospinal fluid, pleocytosis is often observed up to several thousand cells per mm³, usually due to granulocyte-numbered cells, as well as an increased protein concentration, up to several hundred mg / dL.

CAM can develop more often when using immunoglobulin for intravenous administration in high doses (2 g / kg).

Thromboembolic complications

There are clinical data on the relationship between the use of human immunoglobulin for intravenous administration and the occurrence of thromboembolic complications, such as myocardial infarction, acute cerebrovascular accident (including stroke), pulmonary thromboembolism and deep vein thrombosis, which are presumably associated with a relative increase in blood viscosity at administration of a large number of immunoglobulins. Caution should be exercised when administering and administering immunoglobulin infusions for intravenous administration to obese patients and patients with previously established risk factors for thrombotic complications such as advanced age, arterial hypertension, diabetes mellitus,thromboembolism or cardiovascular disease in history, cases of hereditary or acquired thrombophilia, prolonged period of mobility impairment, patients with severe hypovolemia and patients with diseases in which an increase in blood viscosity is observed.

Acute kidney failure

There were cases of development of acute renal failure in patients who received human immunoglobulin therapy for intravenous administration. In most cases, risk factors such as previous presence of renal failure, diabetes mellitus, hypovolemia, excess weight, concomitant treatment with nephrotoxic drugs or age over 65 years have been identified.

In the case of the development of renal failure, therapy with human immunoglobulin for intravenous administration should be discontinued. Patients at risk of developing acute renal failure or thromboembolic complications should be given immunoglobulin preparations for intravenous administration with a minimum infusion rate and at the lowest possible dose.

Effect on diagnostic tests

After the introduction of immunoglobulins in the patient's blood, the number of different passively transmitted antibodies is temporarily increased, which can lead to a false positive result in serological tests. Passive transfer of antibodies to erythrocyte antigens, for example, A, B and D, can lead to an incorrect result in some serological tests to determine antibodies to erythrocytes (for example, Coombs test), in determining the amount of reticulocytes and in the haptoglobin test. Due to the presence of maltose in the formulation (100 mg / ml), a false positive increase in the concentration of glucose in the blood and urine of the patient is possible.

Safety information for infectious agents

The drug is produced from human plasma. Standard measures to prevent the transmission of infections resulting from 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 made 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. Measures taken to ensure antiviral safety are considered effective for enveloped viruses such as HIV, hepatitis B and C viruses, and for non-enveloped viruses such as hepatitis A virus and paravovirus B19.

An encouraging clinical experience has been obtained indicating that there is no transmission of hepatitis A virus and parvovirus B19 to human immunoglobulin preparations, and it is also believed that the presence of antibodies contributes significantly to viral safety. It is recommended to register the name and serial number of the drug for each use of the drug, which is administered to the patient, to maintain communication between the patient and the drug series.

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

Some undesirable reactions associated with the action of the drug may have an effect on the ability to drive a vehicle or moving machinery.For patients who have experienced adverse drug reactions, vehicle management or moving mechanisms is only possible after the symptoms of unwanted reactions have disappeared.

Form release / dosage:Solution for infusion.

Packaging:

In bottles with a capacity of 50 ml for 25 or 50 ml of the preparation, closed with rubber stoppers and rolled with aluminum caps. Each label is labeled with label paper.

Each bottle with the drug is placed in a pack of cardboard along with instructions for use. In the plywood box or corrugated cardboard, packs and a packing list are placed.

Storage conditions:

Store in a dry, dark place at a temperature of 2 to 10 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000412

Date of registration:09.06.2010 / 25.08.2015

Expiration Date:Unlimited

The owner of the registration certificate:IMMUNO-GEM, CJSC IMMUNO-GEM, CJSC Russia

Manufacturer: & nbsp