Registration number: LS-000412
Trade name: Gabriglobine ® - IgG
Grouping name: human normal immunoglobulin.
Dosage form: solution for infusions
1 ml of 5 % solution contains
Immunoglobulin G (IgG) (at least 98 %) is equivalent to the total content of human plasma protein-50 mg
Maltose – 100 mg
Water for injection-up to 1 ml
Description: transparent colorless or yellowish liquid.
Pharmacotherapeutic group: immunoglobulin
ATX code: J06A02
It is a highly purified immunoglobulin G preparation isolated from blood plasma obtained from at least 1000 healthy donors, individually tested for the absence of antibodies to HIV-1, HIV-2, hepatitis C virus and hepatitis b virus surface antigen. The drug contains IgG class antibodies present in the normal population and has low anti-complementary activity. The active principle is immunoglobulins, mainly of class G (IgG), which have the activity of antibodies of various specificity. The drug normalizes the content of specific antibodies: to cytomegalovirus-at least 1: 800; to herpes simplex virus-at least 1:3200; to influenza virus – at least 1:80.
The distribution of subclasses roughly corresponds to their distribution in native human blood plasma. Optimal doses of the drug can restore the low concentration to normal indications.
The mechanism of action when used according to indications, with the exception of substitution therapy, is not fully explained, but includes an immunomodulatory effect. The drug increases the body's non-specific resistance. During production, the product is not subjected to chemical or enzymatic treatment, does not contain preservatives and antibiotics.
After intravenous injection, the drug is distributed relatively quickly between plasma and extravascular fluid. The balance between the intravascular and extravascular sections is reached 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. IgG complexes are destroyed in the cells of the reticuloendothelial system.
Indications for use
1) Replacement therapy for primary immunodeficiency (PID) with impaired antibody production:
congenital agammaglobulinemia and hypogammaglobulinemia;
General variable immune insufficiency;
severe combined immune insufficiency;
2) Replacement therapy for secondary immunodeficiency:
multiple myeloma with severe secondary hypogammaglobulinemia and recurrent bacterial infections when pneumococcal vaccination is ineffective;
chronic lymphoid leukemia with a severe form of secondary hypogammaglobulinemia and recurrent bacterial infections when preventive antibacterial therapy is ineffective;
congenital acquired human immunodeficiency syndrome (AIDS) in children with recurrent infections;
hypogammaglobulinemia in patients after allogeneic hematopoietic stem cell transplantation;
severe forms of bacterial and viral infections; postoperative complications accompanied by bacteremia; generalized infections (sepsis).
3) as an immunomodulatory agent:
in idiopathic thrombocytopenic purpura (ITP) in children or adults with a high risk of bleeding or before surgery to correct the number of platelets;
in Guillain-Barré syndrome;
in Kawasaki disease;
in other autoimmune diseases (systemic lupus erythematosus, vasculitis);
Contraindications for the use of the drug are:
hypersensitivity to the active substance or any other component of the drug;
hypersensitivity to homologous immunoglobulins, especially in very rare cases of immunoglobulin A (IgA) deficiency, when the patient has IgA antibodies.
In cases of severe sepsis, the only contraindication for use is anaphylactic shock to human blood products in the anamnesis.
Precautions for use
With caution: pregnancy, lactation, has a history of renal failure, diabetes, hypovolemia, obesity, concomitant therapy with nephrotoxic drugs, old age (over 65 years), increased plasma viscosity (hypergammaglobulinemia, hyperfibrinogenemia, sickle cell anemia).
Use during pregnancy and breastfeeding
The safety of using normal human immunoglobulin preparations during pregnancy and breastfeeding has not been studied in controlled clinical studies, so their injection to pregnant women and women during breastfeeding should be performed with caution.
The experience of clinical use of immunoglobulin allows us to conclude that there is no negative impact on the course of pregnancy, on the fetus or on the child during breastfeeding.
Before injection, the drug is warmed to room temperature or body temperature.
The drug should be administered only as 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 the rate of 30-40 drops per minute (1.5-2 ml/min). If well tolerated the infusion rate can be gradually increased
up to 8 mg / kg body weight / min (approximately 10 ml / min). In patients with primary immunodeficiency who have well tolerated substitution therapy with the drug, the rate of infusion can be gradually increased to the maximum value
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 clinical response. The following doses are recommended as a guide.
Replacement therapy for primary immunodeficiency
It is recommended to choose a dosage regimen in which the IgG concentration increases to at least 5-6 g/l (IgG content is determined before subsequent infusion). Equilibrium concentrations are reached 3-6 months after the start of treatment. The recommended starting dose is from 0.4 to 0.8 g / kg of body weight, subsequent doses-at least 0.2 g / kg of body weight every 3-4 weeks. Doses of the drug required to achieve IgG concentrations of 5-6 g / l are from 0.2 to 0.8 g / kg of body weight per month. The interval between doses, when equilibrium concentrations are reached, varies from 3 to 4 weeks. IgG concentrations should be measured to regulate the dose and interval injection.
Replacement therapy for multiple myeloma with severe secondary hypogammaglobulinemia and recurrent bacterial infections when vaccination with pneumococcal vaccine is ineffective; for chronic lymphoid leukemia with severe secondary hypogammaglobulinemia and recurrent bacterial infections when preventive antibacterial therapy is ineffective; for congenital AIDS in children with recurrent infections.
Recommended dosage regimen from 0.2 to 0.4 g / kg of body weight every 3-4 weeks.
Replacement therapy for hypogammaglobulinemia in patients after allogeneic hematopoietic stem cell transplantation
Doses of the drug required to maintain IgG concentration at a level of more than 5 g / l are from 0.2 to 0.4 g / kg of body weight every 3-4 weeks.
Severe 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 use the drug at a dose of 0.2-0.8 g/kg of body weight daily for 3-7 days. With the development of sepsis, the drug is prescribed as soon as possible after the diagnosis of the syndrome in a starting dose of up to 1-2 g/kg of body weight, depending on the patient's condition, then - 0.2-0.8 g/kg of body weight for 3-5 days.
Idiopathic thrombocytopenic purpura
In case of exacerbation, assign from 0.8 to 1 g/kg of body weight on the first day (it is possible to re-introduce this dose once more in the next 3 days) or 0.4 g/kg of body weight daily for 2-5 days. If a relapse occurs, treatment can be repeated.
0.4 g / kg of body weight for 5 days. There is limited experience of use in children.
From 1.6 to 2 g / kg of body weight in separate equal doses for 2-5 days or one dose of 2 g/kg of body weight once. Patients should be prescribed acetylsalicylic acid as concomitant therapy.
Systemic lupus erythematosus, vasculitis
From 0.2 to 0.4 g / kg of body weight daily for 3-10 days.
From 0.03 to 0.04 g / kg of body weight daily for 4 days.
Special patient groups
According to clinical studies, patients with PID and ITP did not require correction of the dosage regimen for children.
Recommendations for dosage regimens are given in the table.
Adverse reactions according to numerous clinical studies on intravenous immunoglobulin preparations, presented below, are listed according to the damage to organs and organ systems and frequency of occurrence. The 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: very rare-anaphylactic reactions (including anaphylactic shock), angioedema, facial edema.
Disorders of the blood and lymphatic system: infrequently-anemia, anisocytosis, leukopenia, hemolysis.
Disorders of the nervous system: very often-headache; infrequently-dizziness, discomfort in the head, drowsiness; rarely-aseptic meningitis.
Disorders of the heart: rare – palpitations (palpitation).
Vascular disorders: often-arterial hypertension; infrequently-arterial hypotension, hot flushes, peripheral vascular disorders; very rarely-thromboembolic complications.
Disorders of the respiratory system, chest and mediastinal organs: infrequently-difficulty breathing, a feeling of tightness in the throat
Disorders of the gastrointestinal tract: often-nausea; infrequently-diarrhea, pain in the epigastrium.
Disorders of the liver and biliary tract: infrequently-hyperbilirubinemia.
Skin and subcutaneous tissue disorders: often-urticaria, rashes; infrequently-itching, night sweats.
Disorders of the musculoskeletal and connective tissue: often-back pain; infrequently-neck pain, pain in the extremities.
Disorders of the kidneys and urinary tract: infrequently-proteinuria.
General disorders and disorders at the injection site: often-chills, fatigue, fever, asthenia, flu – like condition; infrequently-chest pain, General malaise, fever, pain at the injection site.
Laboratory and instrumental data: rarely is the increase in the concentration of bound and unbound bilirubin in the blood, positive direct Coombs test, positive indirect Coombs test, increased activity of lactate dehydrogenase in the blood, decrease in hematocrit, increase of aspartate aminotransferase activity, an increased concentration of blood creatinine, decreased blood pressure, increased blood pressure, increased body temperature, decreased hemoglobin.
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 with other medicines
The drug is not recommended to be diluted with various salt solutions. The use of immunoglobulin can disrupt the formation of immunity when vaccinated with weakened live viral vaccines against measles, rubella, mumps and chickenpox. In this regard, after the introduction of immunoglobulin, vaccination against these infections is carried out no earlier than 3 months. After vaccination against these infections, immunoglobulin preparations should be administered no earlier than 2 weeks; if necessary, the use of immunoglobulin before this period, the vaccination should be repeated. In the case of measles, the decrease in the effectiveness of the vaccine can last for 1 year. Therefore, in patients vaccinated against measles, it is necessary to monitor the level of antibodies.
Vaccinations against other infections can be carried out at any time before or after the introduction of immunoglobulin.
Immunoglobulin therapy can be combined with antibiotics, hormones, cytokines, and bacteriophages.
The drug should not be used after the expiration date.
The drug is intended for single use. After opening the bottle, the consumer is responsible for the duration of storage conditions. The solution does not contain preservatives. Partially used drug is not subject to storage and use.
In the case of turbidity of the infusion solution or the presence of mechanical inclusions in the solution, the drug is not subject to use.
The sites of infusions should be provided with antishock therapy.
Unused medication and supplies should be disposed of in a suitable manner.
During the infusion of the drug, the patient's condition should be carefully monitored.
Some adverse reactions may occur more frequently:
- in case of high speed of introduction;
- in patients with hypogammaglobulinemia or agammaglobulinemia with or without IgA insufficiency;
- in patients who receive normal human immunoglobulin therapy for the first time, or in rare cases, when switching to another immunoglobulin drug, or when taking a long break after a previous infusion.
Possible complications can be avoided if you make sure that:
- the patient does not show hypersensitivity to normal human immunoglobulin with slow injection 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 previously received treatment with normal human immunoglobulins, as well as transferred from treatment with another immunoglobulin drug for intravenous injection, or at a long interval after the previous infusion, should be monitored during the first infusion and within the first hour after the first infusion to identify potential adverse events. All other patients should be monitored for at least 30 minutes after injection of the drug.
If an adverse event occurs, reduce the rate of injection or discontinue injection of the drug. The required treatment depends on the nature and severity of the adverse event.
In case of shock, standard treatment for shock conditions should be used.
All patients require appropriate hydration prior to injection of human immunoglobulin for intravenous injection.
True hypersensitivity reactions are rare. They can occur in very rare cases when IgA is deficient with IgA antibodies. Rarely, normal human immunoglobulin can cause a decrease in blood pressure with the development of an anaphylactoid reaction, even in patients who previously tolerated well human immunoglobulin normal therapy.
Human immunoglobulin preparations for intravenous injection may contain antibodies against blood group antigens that can act as hemolysins and bind in vivo to red blood cells, which may cause a positive direct antiglobulin test (Coombs test) and, rarely, hemolysis. Hemolytic anemia can develop after therapy with human immunoglobulin drugs for intravenous injection as a result of increased red blood cell sequestration. Isolated cases of renal dysfunction and/or renal failure or disseminated intravascular coagulation syndrome associated with hemolysis have been reported.
The development of hemolysis is associated with the following risk factors: high doses, regardless of injection as a single dose or individual doses over several days; as well as blood groups A( II), B (III) and AB (IV) in combination with the concomitant presence of an inflammatory process. When treating patients with blood groups A (II), B (III) or AB (IV) with high doses of the drug for indications other than PID, increased caution is recommended.
There are isolated reports of cases of hemolysis in patients with PID receiving substitution therapy. It is necessary to monitor the clinical signs and symptoms of hemolysis in patients receiving therapy with human immunoglobulin preparations for intravenous injection. If signs and/or symptoms of hemolysis occur during or after intravenous immunoglobulin infusions, the attending physician should consider discontinuing further treatment.
The syndrome of aseptic meningitis (HE)
Cases of aseptic meningitis syndrome have been reported during treatment with intravenous immunoglobulin preparations. After the withdrawal of immunoglobulin for intravenous injection, remission occurred within a few days without any consequences. Usually, this syndrome begins within a few hours to 2 days after treatment with intravenous immunoglobulin. When analyzing the cerebrospinal fluid, pleocytosis is often observed up to several thousand cells per mm3, usually due to granulocyte cells, as well as an increased concentration of protein, up to several hundred mg/DL.
Aseptic meningitis syndrome can develop more often against the background of the use of immunoglobulin for intravenous injection in high doses (2 g/kg).
There is clinical evidence of an Association between the use of human immunoglobulin for intravenous injection and cases 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 when a large amount of immunoglobulins is administered. Care should be taken when prescribing and conducting infusions of immunoglobulins for intravenous injection to patients with obesity and patients with previously established risk factors for thrombotic complications, such as old age, hypertension, diabetes, thromboembolism or a history of cardiovascular disease, cases of inherited or acquired thrombophilia, a long period of impaired mobility, patients with severe hypovolemia and patients with diseases in which there is an increase in blood viscosity.
Acute renal failure
Cases of acute renal failure have been identified in patients treated with human immunoglobulin for intravenous injection. In most cases, risk factors were identified, such as previous presence of kidney failure, diabetes, hypovolemia, excess weight, concomitant treatment with nephrotoxic drugs, or age over 65 years.
In the event of renal failure, human immunoglobulin therapy should be discontinued for intravenous injection. In patients at risk of acute renal failure or thromboembolic complications, immunoglobulin preparations for intravenous injection should be injected at the lowest possible rate of infusion and at the lowest possible dose.
Impact on diagnostic tests
After the introduction of immunoglobulins in the patient's blood, the number of various passively transmitted antibodies temporarily increases, which can lead to a false positive result in serological tests. Passive transfer of antibodies to erythrocyte antigens, e.g. A, b and D, can lead to incorrect results in some serological tests for detection of antibodies to red cells (e.g. Coombs test), when determining the number of reticulocytes in haptoglobin test. Due to the presence of maltose in the drug (100 mg/ml), a false positive increase in the concentration of glucose in the patient's blood and urine is possible.
Safety information for infectious agents
The drug is produced from human plasma. Standard measures to prevent transmission of infections resulting from the use of drugs made from human blood or plasma include selecting donors, checking individual donations and plasma pools for specific markers of infection, and including effective production steps aimed at inactivating and/or removing viruses. Despite this, when using drugs made from human blood or plasma, it is impossible to completely exclude the possibility of transmitting infectious agents. 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, as well as for non-enveloped viruses such as hepatitis a virus and parvovirus B19. Encouraging clinical experience has been obtained indicating that there is no transmission of hepatitis a virus and parvovirus B19 with human immunoglobulin preparations, and it is also assumed that the presence of antibodies makes a significant contribution to viral safety. It is recommended to register the name and serial number of the drug that is administered to the patient at each use of the drug, in order to maintain communication between the patient and the drug series.
Influence on the ability to drive vehicles and mechanisms
Some adverse reactions associated with the drug may affect the ability to drive a vehicle or move machinery. For patients who have had adverse reactions during injection of the drug, driving a vehicle or moving machinery is possible only after the symptoms of adverse reactions have disappeared.
Solution for infusions in bottles with a capacity of 50 ml of 25 or 50 ml of the drug, closed with rubber stoppers and rolled with aluminum caps. Each bottle is marked with a label made of label paper. Each bottle of the drug is placed in a pack of cardboard along with instructions for use. In a plywood or corrugated cardboard box, place bundles and a packing list.
Store in a dry, dark place at a temperature of 2 to 10°C.
Keep out of the reach of children.
2 years. Do not use after the expiration date!
They are released by prescription.
Owner of the registration certificate
Moscow, 8, building 2A, Golovinskoe shosse,
Tel / Fax (495) 232-61-74/232-61-75.
Specify the manufacturer's name and address:
"Ivanovo regional blood transfusion station", 5A, Paris Commune street, 153003, Ivanovo
LLC "Immuno-Hem", 610027, Kirov, ul. Krasnoarmeyskaya, d. 70, d. 72
Samara regional clinical blood transfusion station, 156 Novo-Sadovaya street, Samara, 443068
Tambov regional blood transfusion station, 392000, Tambov, Boris Vasiliev str., 3
Chelyabinsk regional blood transfusion station, 68 Vorovsky street, Chelyabinsk, 454076
Complaints about the physical and other properties of the drug should be sent to the owner of the registration certificate and the manufacturer.
General Director of "Immuno-Gem" A. V. Kharchenko