Intraglobin - instructions for use, dose, side effects, contraindications

Active substance:
Proteins of human plasma of them:	50 mg
immunoglobulin G (IgG):	not less than 95%
Distribution of subclasses immunoglobulin G(IgG):
IgG_l	about 62%
IgG₂	about 34%
IgG₃	about 0.5%
IgG₄	about 3.5%

The content of immunoglobulin A (IgA) no more than 2.5 mg

Excipients: dextrose monohydrate - 27.5 mg, sodium chloride - 4.56 mg (sodium ions - 78 μmol, chloride ions - 78 μmol), water for injections - up to 1 ml.

Description:Colorless or light yellow, transparent or slightly opalescent liquid.

Pharmacotherapeutic group:MIBP - globulin

ATX: & nbsp

J.06.B.A.02 Immunoglobulin normal human for intravenous administration

Pharmacodynamics:

Intraglobin contains immunoglobulin G (IgG) with a wide range of antibodies against pathogens of various infections and their toxins. Intraglobin produces from the pool of blood plasma more than 1000 donors, distribution of subclasses IgG corresponds to such a distribution in human plasma. Appropriate doses of Intraglobin allow the pathologically low concentration of immunoglobulins to be brought to a normal level. The mechanism of action for other indications, in addition to replacement therapy in patients with immunodeficiency, consists in immunomodulatory effects,although it is not clear completely.

Pharmacokinetics:Bioavailability of immunoglobulin for intravenous administration is 100%. Distribution between blood plasma and extravascular fluid reaches rather quickly, and in 3-5 days an equilibrium between intravascular and extravascular space is reached. The half-life of Intraglobin is 21.6 ± 1.8 days. The half-life may differ for different patients, especially in the case of primary immunodeficiencies. Immunoglobulins and immunoglobulin complexes are utilized by the cells of the reticuloendothelial system.

Indications:

1. Substitution therapy in adults and children with:

- primary immunodeficiencies:

congenital agammaglobulinemia or hypogammaglobulinemia;
Variable immunodeficiency;
severe combined immunodeficiency;

- chronic lymphocytic leukemia or myeloma with severe secondary hypogammaglobulinemia and recurring bacterial infections;

- recurring bacterial infections in children with AIDS

2. Immunomodulation with:

- idiopathic thrombocytopenic purpura (especially acute forms in children):

in adults and children with a high risk of bleeding;
Before the operation to adjust the number of platelets;

- allogeneic bone marrow transplantation;

- the Kawasaki syndrome.

Contraindications:

Hypersensitivity to any component of the drug.

Hypersensitivity to human immunoglobulin, especially in rare cases of a deficiency in the blood of immunoglobulin class A (IgA) and the presence of antibodies against IgA.

Pregnancy and lactation:

The absence of risk of using this drug during pregnancy has not been studied in controlled clinical trials, therefore, it should be used with caution in pregnancy and lactation, although the long experience of medical use of immunoglobulins does not allow expecting any harmful effect on the course of pregnancy, as well as on the fetus and the newborn. The introduced immunoglobulins are secreted from the mother's milk and can facilitate the transfer of protective antibodies to newborns.

Dosing and Administration:

Doses and dosage regimen depend on the indication.

With substitution therapy, the dose should be selected individually depending on the available pharmacokinetic parameters and the clinical response.

The following doses are recommended for adults and children, including newborns:

Substitution therapy for primary immunodeficiencies:

With the dosing regimen, the IgG in plasma, a minimum of 4-6 g / l (definition IgG before the next infusion). After the start of therapy, it takes 3-6 months to reach the equilibrium concentration. The required initial dose to achieve 4-6 g / l IgG in plasma is 8-16 ml (0.4-0.8 g) / kg body weight, followed by a decrease to 4 ml (0.2 g) / kg every 3 weeks.

If there is no sufficient level IgG or an excessively rapid decrease in the index, it is possible to shorten the intervals between administrations.

Replacement therapy for chronic lymphocytic leukemia or myeloma with severe secondary hypogammaglobulinemia and recurring bacterial infections; replacement therapy for recurrent bacterial infections in children with AIDS:

4-8 ml (0.2-0.4 g) / kg body weight with an interval of 3 to 4 weeks in order to increase the pathologically lowered level IgG up to normal values.

If there is no sufficient level IgG or an excessively rapid decrease in the index, it is possible to increase the dose to 16 ml (0.8 g) / kg of body weight or shorten the intervals between the administrations.

Idiopathic thrombocytopenic purpura:

When treating acute episodes at the first administration, the drug is prescribed in a dose of 16-20 ml (0.8-1 g) / kg body weight and, if necessary, repeated on the second or third day or 8 ml (0.4 g) / kg body weight body a day for 2-5 days in a row. In both cases, if necessary, therapy can be repeated.

Allogeneic bone marrow transplantation:

Therapy with immunoglobulins can be carried out as part of conditioning and after transplantation. To treat infection and prevent the "graft versus host" reaction, the dose should be selected individually. The recommended initial dose is 10 ml (0.5 g) / kg body weight and is administered 7 days before transplantation. Introduction continues weekly for up to 3 months after transplantation. With persisting immunodeficiency, up to the normalization of the level of antibodies, a dose of 10 ml (0.5 g) / kg of body weight per month is recommended.

Kawasaki Syndrome:

32-40 ml (1.6-2 g) / kg body weight, in several doses for 2-5 days or 40 ml (2 g) / kg body weight in a single dose, in addition to acetylsalicylic acid therapy.

Method of administration

Before the introduction of Intraglobin it is necessary to visually check the contents of the vial.The solution should be transparent or slightly opalescent. An opaque or precipitating solution should not be used.

Before administration, the preparation should be warmed to room temperature or body temperature.

Intraglobin is intended for intravenous infusion.

The initial infusion rate should not exceed 30 drops / min (corresponding to 1.4 ml / kg of body weight / hour), after 10 minutes with good drug tolerance, the rate can be gradually increased to a maximum of 40 drops / min (corresponding to 1.9 ml / kg body weight / hour) and keep it until the end of the injection.

Intraglobin can be mixed only with 0.9% sodium chloride solution.

Other drugs can not be added to the Intraglobin solution, since a change in the electrolyte concentration or the pH value can cause denaturation or precipitation of the protein.

The contents of the opened vials should be used immediately. Because of the risk of bacterial contamination, the unused solution must be discarded.

Side effects:

Possible side effects such as chills, headache, fever, nausea, vomiting, allergic reactions, arthralgia and moderate pain in the lower back.

In rare cases, as a result of the introduction of immunoglobulin, sudden lowering of blood pressure, lowering of arterial pressure and, in isolated cases, anaphylactic shock, even if the patient did not show increased sensitivity during the previous administration of the drug, is possible.

In connection with the introduction of immunoglobulins, there have been cases of the appearance of signs of aseptic meningitis and, in rare cases, hemolytic anemia / hemolysis, as well as a transient skin reaction (rash or hyperemia) that completely disappeared after discontinuation of therapy. An increase in serum creatinine and / or acute renal failure was also observed.

In isolated cases, there were thromboembolic reactions, such as myocardial infarction, stroke, pulmonary embolism, and deep vein thrombosis.

In case of occurrence of reactions of intolerance it is necessary either to reduce the speed of administration of the drug, or to stop its infusion before the disappearance of symptoms. The choice of appropriate interventions depends on the type and severity of the side effect.

In the case of a negative effect on kidney function, immunoglobulin therapy should be discontinued.

In the event of a shock, it is necessary to follow the current recommendations for antishock therapy.

When using drugs from human blood or plasma due to the transmission of infectious agents, infection by the latter can not be completely ruled out. This concerns pathogens that are still unknown in nature.

To reduce the risk of transmission of pathogens, donor criteria are selected according to strict criteria, donor plasma is tested and selected and the pool of plasma is monitored. Stages for the removal and / or inactivation of pathogens are included in the production process (see "Additional data").

Overdose:

Overdose of the drug in patients at risk, especially in elderly people and patients with impaired renal function, can lead to hypervolemia (increase in the volume of circulating blood) and increase the viscosity of the blood.

Interaction:

Live (attenuated) viral vaccines

The introduction of immunoglobulins can adversely affect a minimum of 6 weeks and up to 3 months on the effectiveness of live attenuated vaccines against viral diseases such as measles, rubella, mumps and chicken pox.

Vaccination with a suitable live attenuated vaccine should be given no earlier than 3 months after the introduction of Intraglobin. The interval between the introduction of immunoglobulin and measles vaccine can be increased to 1 year. In this regard, patients who need to be vaccinated against measles before the expiration of this period, it is necessary to first examine for the presence of specific antibodies.

Special instructions:

Precautions for use

Certain severe side effects may depend on the rate of administration, so the rate of administration recommended in the section "Dosage regimen, mode of administration" should be strictly observed.

Certain side effects can occur more often:

- at a high rate of administration;

- in patients with hypogammaglobulinemia or agammaglobulinemia in the presence or absence IgA-deficiency;

- in patients receiving human immunoglobulin for the first time, or in rare cases when switching to another immunoglobulin preparation, or if treatment with immunoglobulins has been carried out for a long time.

True hypersensitivity reactions occur in extremely rare cases, in which there is no immunoglobulin in the blood A (IgA) and there are antibodies to IgA.

In rare cases, as a result of the introduction of immunoglobulin, it is possible to lower blood pressure and, in isolated cases, anaphylactic shock, even if the patient did not show hypersensitivity during the previous administration of the drug.

In most cases, possible complications can be avoided if it is ascertained that the patient does not exhibit allergic reactions to human immunoglobulins, first introducing the human immunoglobulin very slowly (0.024 ml / kg / min) carefully during the entire administration of the drug to the patient and to monitor the appearance of symptoms undesirable action. Especially it is necessary to observe especially during the whole infusion and at least 1 hour after its termination in order to control the possible appearance of symptoms of side effects for patients who have never received immunoglobulins from humans or who have received other immunoglobulins to date or who received immunoglobulins very long ago . All other patients should be monitored for at least 20 minutes after administration, pay attention to the glucose content (0.5 g / g IgG) in the drug when administered to patients with latent diabetes mellitus (with the appearance of glucosuria), diabetes mellitus, or patients on a diet low in sugar.

There are suspicions about the relationship between the administration of intravenous immunoglobulins and the phenomena of thromboembolism, such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis. It is suggested that in patients at risk, the administration of a high dose of immunoglobulin leads to a relative increase in blood viscosity.

It is recommended, carefully prescribe and administer immunoglobulins to the following patients: the elderly, high blood pressure, diabetes, vascular disease or history of thrombosis in the anamnesis, hereditary or acquired thrombophilic disorders, patients who have been immobile for a long time, with severe hypovolemia, as well as patients with diseases , increasing the viscosity of the blood.

In patients with the introduction of immunoglobulins, very rare cases of acute renal failure can occur. In most cases, this side effect has occurred in patients,with additional risk factors: existing violations of kidney function, diabetes mellitus, reduced circulating blood volume, overweight, taking drugs that have nephrotoxic effect, and also age over 65 years.

When prescribing the drug and carrying out immunoglobulin treatment for all groups of patients, it is necessary:

- sufficient fluid intake before the infusion of immunoglobulin;

- monitoring the amount of urine;

- control of serum creatinine content (indicator of kidney function) refusal of simultaneous intake of diuretics.

In the event of a negative effect on kidney function, consideration should be given to stopping the administration of immunoglobulin.

Most often, renal dysfunction and acute renal failure are associated with the use of drugs containing sucrose as a stabilizer. Therefore, patients with any risk factor are encouraged to use immunoglobulins that do not contain sucrose, such as Intraglobin. In addition, the immunoglobulin preparation should be administered without exceeding the rate of 0.024 ml / kg / min.

Laboratory research

After the introduction of immunoglobulin, a temporary increase in the titer of various passively introduced antibodies is possible, which can lead to false positive results in serological testing.

Passively introduced antibodies against erythrocyte antigens (eg, A, B, D) can affect individual serological parameters, such as alloantibodies to erythrocytes (eg, Coombs reaction), the number of reticulocytes and haptoglobin.

Additional information

For the production of Intraglobin, only plasma of healthy donors is used, in which no antibodies to HIV type 1 and 2 have been detected, to hepatitis C virus and the surface antigen of the hepatitis B virus, and also the activity of liver enzymes (transaminase) does not exceed the normal limit value. In addition to testing the plasma of individual donors, miniipules are first tested (testing by PCR for HIV, hepatitis A, B and C viruses, parvovirus 19), and then the production pool of plasma processed for Intraglobin (re-testing for antibodies to HIV-1/2, hepatitis B and C viruses, as well as the PCR method for HIV, hepatitis B and C viruses).In production, a pool of plasma is used only with negative test results.

Intraglobin is made by fractionation of ethanol in the cold. In addition, the manufacturing process includes the steps of removing and inactivating viruses (adsorption on aerosil, treatment βpropiolactone and filtration).

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

There is no indication that immunoglobulins can affect the ability to drive vehicles or service mechanisms.

Form release / dosage:Solution for infusions, 50 mg / ml.

Packaging:

For 10 ml or 20 ml of the drug in ampoules of colorless glass.

For 50 ml or 100 ml of the drug in bottles of colorless glass, ukuporennyh cork rubber and aluminum cap.

For 1 ampoule or 1 bottle in a cardboard box with instructions for use.

Storage conditions:

Store in a dark place at a temperature of 2 to 8 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

The drug with expired shelf life is not subject to application.

Terms of leave from pharmacies:On prescription

Registration number:П N011844 / 01

Date of registration:20.07.2011

Expiration Date:Unlimited

The owner of the registration certificate:Biotest Pharma GmbHBiotest Pharma GmbH Germany

Manufacturer: & nbsp

BIOTEST PHARMA, GmbH Germany

Representation: & nbspBIOTEST PHARMA GmbHBIOTEST PHARMA GmbHRussia

Information update date: & nbsp27.10.2017

Illustrated instructions

Instructions

Intraglobin (Intraglobin)