Immunoglobulin Sigardis MT - instructions for use, dose, side effects, contraindications

Distribution of subclasses IgG approximately corresponds to their distribution in normal human plasma. 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.

The drug is produced from plasma obtained from no less than 1000 donors. The drug contains antibodies of class IgG, present in a normal population.

Pharmacokinetics:

Suction

Bioavailability of the drug after intravenous administration is 100%.

Distribution

The drug is rapidly distributed between plasma and extraovascularcthat liquid. The equilibrium state is reached on day 3-5.

Metabolism

Immunoglobulin G and complexes IgG are destroyed in the cells of the reticulo-endothelial system.

Excretion

The half-life is about 28 days and can vary in different patients, especially in people with primary immunodeficiency.

Indications:

Substitution therapy with:

1) Primary immunodeficiencies (FID), such as:

- Congenital agammaglobulinemia and hypogammaglobulinemia;

- General variable immune deficiency;

- Severe combined immune deficiency;

- Wiskott-Aldrich syndrome.

2) Multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective vaccination with pneumococcal vaccine.

3) Chronic lymphoid leukemia with severe secondary hypogammaglobulinemia and recurrent bacterial infections with ineffective prophylactic antibacterial therapy.

4) Congenital syndrome of acquired human immunodeficiency (AIDS) in children in the presence of recurrent infections.

5) Hypogammaglobulinemia in patients after allogeneic transplantation of hematopoietic stem cells.

As an immunomodulating agent with:

1) Idiopathic thrombocytopenic purpura (ITP) in adults and children with high risk of bleeding or before surgery to correct the number of platelets

2) Guillain-Barre Syndrome

3) Diseases of Kawasaki

Contraindications:

Hypersensitivity to the components of the drug.

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

Pregnancy and lactation:

The safety of the drug during pregnancy and the period of breastfeeding in controlled clinical trials has not been established. Therefore, the drug should be used with caution during pregnancy and the period of breastfeeding.

Immunoglobulins penetrate the placenta, especially in the third trimester of pregnancy. Immunoglobulins are excreted in breast milk, while antibodies can have a protective effect in a newborn.

The appearance of adverse effects on the course of pregnancy, fetus or on the newborn on the basis of clinical experience with the use of immunoglobulins is unlikely.

Dosing and Administration:

Intravenously.

Before administration, the temperature of the drug should be brought to room temperature or the patient's body temperature. The drug is administered intravenously with an initial rate of 0.75-1.0 ml / min (15 drops / min) for 15 minutes, in the next 15 minutes - 1.2-1.5 ml / min (25 drops / min). If no undesirable reactions were noted, the rate of administration of the remainder of the drug can be increased to the maximum possible - 3 ml / min (54 drops / min).

Doses 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 used:

Substitution therapy for primary immunodeficiencies

It is recommended to choose a dosing regimen in which the concentration IgG increases to a minimum of 4-6 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 initial dose is 0.4-0.8 g / kg body weight, subsequent doses - not less than 0.2 g / kg body weight every 3 weeks. The dose necessary to achieve concentration IgG 6.0 g / l, is from 0.2 to 0.8 g / kg body weight per month.

The interval between administrations, when equilibrium concentrations are reached, is from 2 to 4 weeks.

For the most accurate determination of the administered doses, periodic measurement of the concentration IgG.

Replacement therapy for multiple myeloma with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections; chronic lymphoid leukemia with severe form of secondary hypogammaglobulinemia and recurrent bacterial infections; 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.

Hypogammaglobulinemia in patients after allogeneic transplantation of hematopoietic stem cells

The dose of the drug necessary to maintain concentration IgG at a level of more than 5 g / l, is 0.5 g / kg body weight every 3-4 weeks.

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 daily 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.

Recommendations for dosing regimens are given in the following table:

Indications	Doses	Interval between infusions
Substitution therapy
Primary immunodeficiencies	Starting dose: 0.4-0.8 g / kg body weight Further: 0.2-0.8 g / kg body weight	Once, every 2-4 weeks before reaching the concentration IgG not less than 4-6 g / l.
Secondary immunodeficiencies	0.2-0.4 g / kg body weight	Once, every 3-4 weeks until the concentration is reached IgG not less than 4-6 g / l.
Children with congenital AIDS in the presence of recurrent infections	0.2-0.4 g / kg body weight	Once, every 3-4 weeks.
Hypogammaglobulinemia (<4 g / l) in patients after allogeneic transplantation of hematopoietic stem cells	0.5 g / kg body weight	Once, every 3-4 weeks, to maintain concentration IgG more than 5 g / l.
Application as an immunomodulator
Idiopathic thrombocytopenic purpura	0.8-1 g / kg body weight Or: 0.4 g / kg body weight	On the first day, it is possible to repeat a single administration for 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 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 of acetylsalicylic acid. Once, in combination with the appointment of acetylsalicylic acid.

Side effects:

Depending on the frequency of occurrence, the following groups of side effects are identified: very often (≥ 1/10), often (from ≥ 1/100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely from ≥ 1/10000 to <1/1000), very rarely (<1/10000, including individual messages).

Infrequent reactions such as chills, headache, fever, vomiting, allergic reactions, nausea, joint pain, lowering blood pressure, and moderate back pain were rare.

Rarely, hypersensitivity reactions with a sharp decrease in blood pressure and, in some cases, anaphylactic shock, even when the patient has not previously been shown a hypersensitivity reaction with the use of the drug.

Cases of reversible aseptic meningitis and, in rare cases, temporary skin reactions were observed in patients after using human immunoglobulin. Hemolytic reactions were observed in patients with blood groups A (II), B (III) and AB (IV). Hemolytic anemia requiring blood transfusion can rarely occur after treatment with high doses of human immunoglobulin preparations for intravenous administration (see section "Special instructions").

There have been cases of increased serum creatinine concentration and / or acute renal failure.

Very rarely there were thromboembolic complications, such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis.

Some patients during the infusion may experience such undesirable reactions as transient headache, rapid heartbeat, nausea, which may be associated with too high a speed of infusion or individual features of the patient's body.Most of these unwanted reactions are mild and usually occur during the first hour of infusion.

Infectious and parasitic diseases: infrequently - an infection of the ENT organs (otitis media, nasopharyngitis), influenza.

Violations of the blood and lymphatic system: infrequently - anemia, anisocytosis, leukopenia, hemolysis.

Disturbances from the nervous system: very often - headache; infrequent - dizziness, discomfort in the head, drowsiness, tremor, sinus headache, migraine, dysesthesia; very rarely confusion.

Heart Disease: infrequent - palpitations (palpitation).

Vascular disorders: often - arterial hypertension; infrequently - arterial hypotension, hot flashes, peripheral vascular disorders.

Disturbances from the respiratory system, chest and mediastinal organs: infrequent - difficulty breathing, the formation of bubble cells on the mucous membrane of the mouth and throat, pain in breathing, a feeling of restraint in the throat.

Disorders from the gastrointestinal tract: often - vomiting, nausea; infrequently - diarrhea, pain in epigastrium.

Disturbances from the liver and bile ducts: infrequently hyperbilirubinemia.

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

Disturbances from musculoskeletal and connective tissue: often - pain in the back; infrequently - pain in the neck, pain in the limbs, rigidity of muscles, muscle spasms, pain in muscles and bones, muscle weakness.

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 activity of alanine aminotransferase, an increase in activity of aspartate aminotransferase, an increase in the concentration of creatinine, a decrease in blood pressure, , an increase in body temperature, a decrease in hemoglobin.

Overdose:

Symptoms: water retention in the body, increased blood viscosity (especially in patients with impaired renal function or in old age).

Treatment: symptomatic.

Interaction:

Possible dilution of the drug 5% solution of dextrose if necessary. In this case, care should be taken when prescribing the drug to patients with diabetes mellitus.

Live attenuated viral vaccines

The introduction of immunoglobulins can adversely affect from 6 weeks and up to 3 months on the action of live vaccines against such viral diseases as measles, rubella, mumps and chicken pox. Vaccination with live vaccine should be given no earlier than 3 months after the administration of the drug.

In the case of measles vaccination, the effect of immunoglobulin can last up to 1 year. In this regard, patients vaccinated with measles vaccine, it is necessary to control the level of specific antibodies.

Special instructions:

The drug should be administered only as an intravenous infusion.

During the dilution of the drug, the technique of working in aseptic conditions must be strictly observed.

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

The drug is intended for single use.The contents of the vial should be used immediately after opening.

For all patients receiving intravenous immunoglobulins, adequate hydration should be performed before starting the infusion.

The established severe adverse reactions can be associated with the rate of drug administration, hypo- and agammaglobulinemia (against a background of deficiency of immunoglobulin A or without it), with the introduction of immunoglobulin for the first time or, in rare cases, transfer to the introduction of another immunoglobulin or occur after a long period after the last infusion. It is necessary to carefully observe the speed of administration of the drug, indicated in the section "Method of administration and dose". It is necessary to carefully monitor patients and monitor for any symptoms during the infusion period.

Particular care should be taken of patients who have not previously received immunoglobulin preparations treated with an alternative drug, or after a long interval after the last injection of an immunoglobulin. Such patients should be observed during the entire period of the first infusion of the drug,and also within 1 hour after the end of the administration. The remaining patients should be observed at least within the first 20 minutes after application of the drug.

In case of development of undesirable phenomenon it is necessary to reduce speed or to stop introduction of a preparation. 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.

Hypersensitivity

True hypersensitivity reactions are rare. They can occur in very rare cases of deficiency IgA, if the patient has 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 the infusionimmunoglobulin for intravenous administration, the treating physician should consider canceling 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 body weight).

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 when a large number of immunoglobulins are administered. Caution should be exercised when administering and administering immunoglobulins 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 a history of cardiovascular disease, cases of hereditary or acquired thrombophilia, prolonged period of mobility impairment, patients with severe hypovolemia and patients with diseases in which n It is observed increase in blood viscosity.

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 the wrong result in some serological tests for the determination of antibodies to erythrocytes (for example, Coombs test), in the determination of reticulocytes and in the haptoglobin test.

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 the selection of donors,checking 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. Clinical experience indicates the absence of transmission of hepatitis A virus and parvovirus B19 with human immunoglobulin preparations, and it is also assumed 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.

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

Some unwanted reactions associated with the action of the drug may affect the ability to drive vehicles or mechanisms. For patients who have experienced adverse drug reactions, vehicle management is only possible after the symptoms of unwanted reactions have disappeared.

Form release / dosage:

Solution for infusions, 50 mg / ml.

Packaging:

For 100 ml (5 g of active ingredient) in a glass colorless vial closed with a rubber stopper and an aluminum cap covered with a plastic cap of blue color.

1 bottle together with instructions for medical use in a cardboard box.

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:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003709

Date of registration:28.06.2016

Expiration Date:28.06.2021

The owner of the registration certificate:SIGARDIS ENG, LLCSIGARDIS ENG, LLC Russia

Manufacturer: & nbsp

Sichuan Yuanda Shuyang Pharmaceutical, Co.Ltd China

Representation: & nbspSigardis Rus, Open CompanySigardis Rus, Open Company

Information update date: & nbsp08.11.2017

Illustrated instructions

Instructions

Immunoglobulin Sigurdis MT (Immunoglobulin Sigurdis MT)