Intratect - instructions for use, doses, side effects, contraindications

Intratect contains mainly immunoglobulin G (IgG) with a wide range of antibodies against various pathogens of infections. Intratect produce from the pool of plasma more than 1000 donors, distribution of subclasses IgG corresponds to that in human plasma. Immunological properties in the introduction of Intratecht allow the pathologically low concentration of immunoglobulins to reach a normal level. The mechanism of action for other indications, except for replacement therapy, is not completely clear and, apparently, consists in immunomodulating effect.

Pharmacokinetics:

Bioavailability of immunoglobulin for intravenous administration is 100%. Distribution between plasma and extravascular fluid is achieved quickly enough, and in 3-5 days an equilibrium is achieved between the intravascular and extravascular space. The half-life of the Intratect in patients with primary immunodeficiency is approximately 27 days. The half-life may differ for different patients, especially in the case of primary immunodeficiencies.

Immunoglobulin G and IgG complexes are utilized by cells of the reticuloendothelial system.

Indications:

1. Substitution therapy

- with congenital immunodeficiency:

complete or selective immunodeficiency;
general variable immunodeficiency;
severe combined immunodeficiency;
Wiskott-Aldrich syndrome;

- with chronic lymphatic leukemia and myeloma with severe secondary selective, immunodeficiency, and recurrent bacterial infections;

- in children with AIDS, as well as with recurrent bacterial infections.

2. Immunomodulation with:

- idiopathic thrombocytopenic purpura in adults and children at high risk bleeding before surgery to adjust the number of platelets;

- Guillain-Barre syndrome;

- Kawasaki syndrome.

3. Allogeneic bone marrow transplantation.

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:

Dosages and intervals between infusions depend on the indication.

With substitution therapy, the dose should be selected individually, depending on the patient's immune status and the severity of the disease.

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

Substitution therapy for primary immunodeficiencies

The initial dose is 0.4-0.8 g (8-16 ml) / kg body weight, then the drug is administered every 3 weeks at a dose of 0.2 g (4 ml) / kg body weight. The required dose to maintain the IgG titer in plasma at a level of 6 g / l is 0.2-0.8 g (4-16 ml) / kg body weight per month. After reaching the equilibrium concentration, the drug is administered at intervals of 2-4 weeks. To determine the optimal dose and the interval between administrations, the level of IgG in the plasma should be monitored.

Substitution therapy for chronic lymphocytic leukemia, myeloma with severe secondary hypogammaglobulinemia and recurrent bacterial infections; substitution treatment in children with AIDS and with recurrent bacterial infections

The recommended dose is 0.2-0.4 g (4-8 ml) / kg body weight every 3-4 weeks

Idiopathic thrombocytopenic purpura

In the treatment of acute episodes, the drug is prescribed in a dose of 0.8-1 g (16-20 ml) / kg of body weight, if necessary repeat this dose on the third day or 0.4 g (8 ml) / kg of body weight per day for 2-5 days in a row. If necessary, therapy can be repeated.

Guillain-Barre Syndrome

0.4 g (8 ml) / kg body weight daily for 3-7 days.

Kawasaki Syndrome

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

Allogeneic bone marrow transplantation

Therapy Intreatect can be carried out as part of conditioning and after transplantation. To treat infection and prevent the "graft versus host" reaction (rejection of the graft), the dose should be selected individually. The recommended initial dose of 0.5 g (10 ml) / kg body weight is administered once seven days before transplantation. Introduction continues weekly up to 3 months after transplantation. If immunodeficiency persists, a dose of 0.5 g (10 ml) / kg of body weight once a month is recommended until the level of antibodies is normalized.

Recommendations for dosing are summarized in the table:

Indication	Dose	Intervals between infusions
Substitution therapy:
With primary immunodeficiencies	Initial dose: 0.4-0.8 g / kg body weight,
	Then: 0.2-0.8 g / kg body weight	Every 3 weeks for the level IgG in plasma, a minimum of 4-6 g / l
With secondary immunodeficiencies	0.2-0.4 g / kg body weight	Every 3-4 weeks for the level IgG in plasma, a minimum of 4-6 g / l
Children with AIDS	0.2-0.4 g / kg body weight	Every 3-4 weeks for the level IgG in plasma, a minimum of 4-6 g / l
Immunomodulation:
Idiopathic thrombocytopenic purpura	0,8-1,0 g / kg body weight	In a single dose, if necessary, repeatedly in a single dose on the third day
	or 0.4 g / kg body weight / day	2-5 days in a row
Guillain-Barre Syndrome	0.4 g / kg body weight / day	3-7 days in a row
Kawasaki Syndrome	1.6-2.0 g / kg body weight	In several receptions for 2-5 days as an addition to . therapy with acetylsalicylic acid
	or 2.0 g / kg body weight	In a single dose as a supplement to therapy with acetylsalicylic acid
Allogeneic bone marrow transplantation:
Therapy of infection and the prevention of the reaction "graft versus host"	0.5 g / kg body weight	Weekly, starting therapy 7 days before and ending 3 months after transplantation
Retaining immunodeficiency	0.5 g / kg body weight	Monthly before the normalization of the level of antibodies

Method of administration

Before the introduction of the IntraText, you need 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. Intratect is intended for intravenous infusion, the drug is administered drip. The initial infusion rate should be 1.4 ml / kg body weight / hour, after 30 minutes with good drug tolerance, the rate of administration can be gradually increased to a maximum of 1.9 ml / kg body weight / hour and stored until the end of the injection.

Note:

Intratect should not be confused with other drugs. Do not add any other preparations to Intratext solution, as changing the electrolyte concentration or pH value can cause protein denaturation or precipitation.

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, a sudden decrease in blood pressure and, in isolated cases, anaphylactic shock, even if the patient did not show increased sensitivity during the previous administration of the drug.

If signs of aseptic meningitis and rare cases of haemolytic anemia / haemolysis, and transient skin reactions (rash or redness), which are fully reversible after discontinuation of therapy due to the introduction of human immunoglobulin were observed. An increase in serum creatinine and / or acute renal failure was also observed.

In a few cases we noted 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 case of shock, follow the current recommendations for anti-shock therapy.

Overdose:

An overdose of the drug in patients belonging to a risk group, especially in the elderly and patients with impaired renal function, may lead to fluid overload (increasing the volume of circulating blood) and increasing 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 an appropriate live vaccine should be carried out no earlier than 3 months after the introduction of the IntraTect. 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, both in the presence and absence of IgA deficiency;

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

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

In rare cases, after administration of immunoglobulin, a decrease in blood pressure is possible, and in some 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:

- make sure that the patient does not have allergic reactions to human immunoglobulin for very slow administration (0.024 ml / kg / min);

- closely monitor during the entire injection of the drug for the patient and monitor the appearance of signs of undesirable effects. 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 the end of the injection.

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 to carefully prescribe and administer immunoglobulins to the following patients: the elderly, high blood pressure, diabetes mellitus, vascular disease or history of thrombosis in an ancestral hereditary or acquired thrombophilic disorders, patients who have been immobile for a long time, with severe hypovolemia, and patients with diseases that increase the viscosity of the blood.

Single cases of acute renal failure after the introduction of intravenous immunoglobulins, which occurred in patients with additional risk factors: renal dysfunction, diabetes mellitus, reduced circulating blood volume, overweight, taking drugs that have nephrotoxic effect, and also age over 65 years are described. .In the case of a violation of the kidneys should decide whether to abolish immunoglobulin therapy.

Patients who are at risk of acute renal failure or thromboembolism immunoglobulin drug should be administered with the lowest possible speed and in the lowest possible dose.

When treating with immunoglobulin for all groups of patients it is necessary:

- sufficient fluid intake before the infusion of the drug;

- monitoring the amount of urine;

- control of serum creatinine content;

- To exclude simultaneous reception of diuretics (especially diuretics).

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 administered antibodies against erythrocyte antigens (e.g., A, B, D) may affect the individual serological parameters such as alloantibodies to erythrocytes (e.g., Coombs' test), haptoglobin and reticulocyte count.

Additional information

When using drugs from human blood or plasma due to transmission of pathogens of infectious diseases completely eliminated. This also applies to causative agents of a still unknown 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.

The production process includes stages for the removal and / or inactivation of pathogens.

For the production of the Intratect, only the plasma of healthy donors is used, in which no antibodies to HIV type 1 and 2 have been detected, the hepatitis C virus and the hepatitis B surface antigen, as well as the activity of liver enzymes (transaminase) do not exceed the normal limit value. In addition to testing the plasma of individual donors, miniipules are first subjected to control (testing by PCR for HIV, hepatitis A, B and C viruses, parvovirus 19), and then the production pool of plasma processed for Intratect (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.

The intratect is made by fractionating ethanol in the cold.

In addition, validated stages of virus removal and / or inactivation are included in the production process (treatment with octanoic acid and calcium acetate, as well as solvent / detergent treatment and filtration).

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

There is no indication that immunoglobulins can affect the ability of manage vehicles or service machinery.

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

Packaging:

To 20 ml, 50 ml, 100 ml or 200 ml in vials of colorless glass (EF, type of glass 2) sealed with a cork made of bromobutyl rubber (EF, type of plug 1) and an aluminum cap.

The cardboard box is sealed from above with a self-adhesive film (control of the first opening).

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

Storage conditions:

Store at a temperature of no higher than 25 ° C in a dark place, 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:LS-002353

Date of registration:17.08.2011

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: & nbsp14.10.2015

Illustrated instructions

Instructions

Intratect (Intratect)