Index of drugs

The drug can be used in all age ranges, unless otherwise specified below.Substitution treatment: primary immune deficiencies with abnormal antibody production; hypogammaglobulinaemia with recurrent bacterial infections in patients with chronic lymphocytic leukemia in which prophylactic antibiotic therapy has been shown to be ineffective; hypogammaglobulinaemia with recurrent bacterial infections in patients with multiple myeloma plateau who did not respond to pneumococcal vaccination; hypogammaglobulinaemia in patients after transplantation of allogeneic hemapoietic stem cell (HSCT); recurrent bacterial infections in congenital immunodeficiency (AIDS).immunomodulation: Immunological thrombocytopenic purpura (ITP) in patients at high risk of bleeding or before surgery, when correction of platelet count is necessary; Guillain-Barré syndrome, Kawasaki disease.

50 mg / ml solution: 1 ml of solution contains 50 mg of normal human immunoglobulin (including at least 97% IgG). Distribution of IgG subclasses: IgG1 - 66.6%, IgG2 - 28.5%, IgG3 - 2.7%, IgG4 - 2.2%. The maximum IgA content is 50μg / ml. 1 ml of solution contains 50 mg of D-sorbitol.A solution of 100 mg / ml: 1 ml of solution contains 100 mg of normal human immunoglobulin (including at least 97% IgG). Distribution of IgG subclasses: IgG1 - 66.6%, IgG2 - 27.9%, IgG3 - 3.0%, IgG4 - 2.5%. The maximum IgA content is 100 μg / ml. 1 ml of solution contains 50 mg of D-sorbitol.

Normal human immunoglobulin contains mainly a functionally unaltered immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents. It has a distribution of immunoglobulin G subclasses strictly proportional to that occurring in natural human plasma. Sufficiently high doses of normal human immunoglobulin can restore abnormally low concentration of immunoglobulin G to the normal range. The mechanism of action of a drug administered for indications other than substitution treatment has not been fully elucidated, but is known to include immunomodulatory effects. Normal human immunoglobulin after intravenous administration is characterized by immediate and full bioavailability in the recipient's circulatory system. It is relatively quickly distributed between plasma and extracellular fluid; after 3-5 days, there is a state of balance between the intra- and extravascular compartments. The average half-life for IgG after administration of the 50 mg / ml preparation is 30-32 days, 100 mg / ml34-37 days. The half-life may vary from individual patients, especially in cases of primary immunodeficiency.

Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to human immunoglobulins when the patient has anti-IgA antibodies. Fructose intolerance.

It is essential to follow the instructions for the method of administration and strictly maintain the recommended infusion rate. The patient's condition should be carefully monitored for adverse reactions during infusion. Certain side effects may occur more frequently with high infusion rates or in patients receiving human normal immunoglobulin for the first time or, in rare cases, when the preparation is changed with human normal immunoglobulin to another or after a longer interval than the previous infusion. Potential complications can be avoided by making sure that patients: do not show hypersensitivity to human normal immunoglobulin, initially giving the formulation at low speed (0.01 ml / kg / min); they are carefully monitored to detect any symptoms during the entire infusion period. In particular, during administration of the first infusion and in the first hour after its completion, patients not previously treated with human normal immunoglobulin should be monitored, patients receiving an alternative Ig iv formulation, or a large time interval from the previous infusion. All other patients should be monitored for at least 20 minutes after administration.If an adverse reaction occurs, reduce the infusion rate or discontinue it. In the event of a shock, appropriate medical treatment should be used. In all patients, intravenous Ig administration requires: adequate hydration of the patient before commencement of intravenous infusion of Ig, monitoring of diuresis, monitoring of serum creatinine, avoidance of concomitant use of loop diuretics. Actual hypersensitivity reactions are rare: they may occur in patients who have anti-IgA antibodies. The drug is not indicated in patients with selective IgA deficiency in whom IgA deficiency is the only abnormality. In rare cases, administration of human immunoglobulin may cause a fall in blood pressure with anaphylactic reaction, even in patients who have previously tolerated treatment with human immunoglobulin. IVIg IV infusion should be used with caution in patients with obesity and in patients with existing risk factors for thrombotic events such as older age, hypertension, diabetes mellitus, vascular disease or previous history of thromboembolism, acquired or congenital thrombophilia, long-term immobilization, severe hypovolemia , diseases in the course of which the viscosity of the blood increases. Cases of renal failure have been reported in patients treated with IVIg, in most cases risk factors such as pre-existing renal failure, diabetes, hypovolemia, overweight, concomitant use of nephrotoxic medicinal preparations, age over 65 years have been identified. In cases of renal dysfunction, discontinuation of IVIg should be considered. Reports of dysfunction and acute renal failure were associated with the use of many approved IVIg products, but preparations containing sucrose as a stabilizer had a disproportionate share in the overall number of cases; for patients at risk, the use of IVIg products that do not contain sucrose may be considered. For patients at high risk of acute renal failure or thromboembolic adverse reactions, IVIg should be administered at the minimum infusion rate and at the lowest doses used. In association with IVIg therapy, aseptic meningitis syndrome (AMS) has been reported; discontinuation of IVIg therapy resulted in remission of AMS within a few days without sequelae. Patients receiving IVIg should be monitored for clinical signs and symptoms of haemolysis. Despite the use of standard methods to prevent infections transmitted via preparations produced on the basis of human blood or plasma, the administration of infectious agents can not be ruled out when such preparations are administered. This also applies to unknown or emerging viruses or other pathogens. The methods used are considered effective in preventing the transmission of enveloped viruses such as HIV, HBV and HCV, and non-enveloped viruses such as HAV and parvovirus B19. Clinical experience indicates that hepatitis A virus or parvovirus B19 is not transmitted via immunoglobulin preparations. It is also presumed that the presence of antibodies contained in them contributes to the safety of these preparations. Due to the sorbitol content, the preparation should not be used in patients with congenital fructose intolerance. In infants and young children in whom intrinsic fructose intolerance may still be undiagnosed and life-threatening, this medicinal product must not be used. The safety and efficacy of the preparation in children from 0 to 2 years of age has not been determined in clinical trials. The safety and efficacy of the 100 mg / ml formulation has been confirmed in clinical trials in children and adolescents aged 3 to 16 in 3 cases of primary immunodeficiency and in 9 cases of ITP.

The safety of the preparation in pregnant women has not been studied in controlled clinical trials. the preparation can be used during pregnancy and during lactation only when it is clearly indicated. It has been shown that products containing IVIg can pass through the placenta, which occurs most severely in the third trimester of pregnancy. Clinical experience in the use of immunoglobulins does not indicate that a negative effect on the course of pregnancy, fetal and neonatal development should be expected.

After intravenous administration of a normal human immunoglobulin, side effects such as chills, headache, dizziness, fever, vomiting, allergic reactions, nausea, arthralgia, moderate back pain and drop in blood pressure may occur.In rare cases, administration of human immunoglobulin may cause a sudden drop in blood pressure and in some cases anaphylactic shock, even when there were no symptoms of hypersensitivity after previous doses. There have been sporadic cases of reversible aseptic meningitis and occasional cases of transient cutaneous reactions. Reversible haemolytic reactions have also been observed, particularly in patients with blood groups A, B or AB. After high doses of IVIg, hemolytic anemia requiring blood transfusion may occur in rare cases. Increases in serum creatinine and / or acute renal failure have been observed. Very rare: thromboembolic reactions such as myocardial infarction, stroke, pulmonary embolism and deep vein thrombosis. Other side effects that may occur after administration of the preparation 100 mg / min: very common: headache; often: tachycardia, hypotension, nausea, back pain, muscle pain, pain, erythema, induration, elevated body temperature; uncommon: influenza, urinary tract infection, bicitopenia, leukopenia, anorexia, dizziness, pain syndrome, syncope, muscle tremor, conjunctivitis, macular degeneration, photophobia, earache, systolic and diastolic hypertension, redness of the skin, hematoma, thrombosis, leakage of secretion from the posterior nostrils, sinus pain, wheezing, increased tension of abdominal integuments, abdominal pain (including the upper part), diarrhea, bloating, vomiting, acne, subcutaneous episodes, erythema, pruritus, rash, joint pain, muscle spasms, increased muscle tone, neck pain, pain in the extremities, discomfort and chest pain, chills, tiredness, cold feeling, anxiety, flu-like symptoms, infusion-related reactions, redness at the infusion site, malaise, peripheral edema, elevated blood pressure, lowering hemoglobin level, acceleration of heart rate. Other side effects that may occur after administration of 50 mg / min: Common: headache, fever, injection site reaction; rare: positive Coombs test, reduced or increased systolic pressure, elevated body temperature, dizziness, bronchitis, cough, wheezing, diarrhea, nausea, vomiting, abdominal pain (including the upper part), urticaria, rash, contact dermatitis , back pain, arthralgia, muscle pain, muscle cramps, hypotension, hypertension, diastolic hypotension, unstable blood pressure, chills, asthenia, pain, inflammation at the infusion site, swelling, pain and redness at the injection site, dislocation of the cannula.

The dose and dosage schedule depend on the indications for use. In replacement therapy, there may be a need to set an individual dose for each patient depending on the pharmacokinetic and clinical response.Substitution treatment of primary immunodeficiency syndromes A dosing schedule should be used to achieve a constant IgG level threshold (level before the Next dose) not lower than 5 - 6 g / l. Achieving a pharmacokinetic balance may require between 3 and 6 months of treatment. The recommended starting dose should be between 0.4 - 0.8 g / kg and the maintenance doses administered should not be less than 0.2 g / kg at intervals of 3 to 4 weeks. To reach the minimum concentration, of 5-6 g / l a dose of 0.2-0.8 g / kg / month is required. The interval between doses after reaching steady-state is 3-4 weeks. It is necessary to determine the threshold levels to adjust the doses depending on the frequency of infection. In order to reduce the frequency of infection, it may be necessary to increase the dose and increase the threshold level.Hypogammaglobulinaemia in chronic lymphocytic leukemia with recurrent bacterial infections in patients for whom prophylactic antibiotic therapy has proved ineffective; hypogammaglobulinaemia with recurrent bacterial infections in patients with multiple myeloma plateau who have not responded appropriately to pneumococcal vaccination; inborn AIDS with recurrent bacterial infections. The recommended dose is 0.2-0.4 g / kg. every 3 or 4 weeksHypogammaglobulinaemia in patients after transplantation of allogeneic stem cells of the hemapoetic system.The recommended dose is 0.2-0.4 g / kg. every 3 or 4 weeks. Minimum concentrations above 5 g / l should be maintained. Immunological thrombocytopenic purpura.Alternatively, two treatment regimens are used: on the first day 0.8 - 1 g / kg; the dose can be repeated if necessary within 3 days or 0.4 g / kg. every day for 2 to 5 days. In case of relapse, treatment can be repeated.Guillain-Barré syndrome. 0.4 g / kg per day for 5 days.Kawasaki disease. It is recommended to administer 1,6 - 2,0 g / kg. in divided doses for 2 to 5 days or 2.0 g / kg in a single dose. Patients should receive Acetylsalicylic acid at the same time.
The 50 mg / ml preparation should be infused into a vein intravenously over the first 30 minutes at a rate of 0.01 - 0.02 ml / kg / min. If the infusion of this dose is well tolerated, the rate can be gradually increased to a maximum of 0.1 ml / kg / min. The 100 mg / ml preparation should be infused into a vein intravenously over the first 30 minutes at a rate of 0.01 ml / kg / min. If the infusion of this dose is well tolerated, the rate can be increased to 0.02 ml / kg / min over the next 30 minutes. Then, when the product is still well tolerated, the rate can be increased for a further 30 minutes to 0.04 ml / kg / min. With further good tolerance, the infusion rate can be increased by a further 0.02 ml / kg / min at 30-minute intervals up to a maximum of 0.08 ml / kg / min. In patients with adverse reactions, it is recommended to release the infusion rate to a maximum speed of not more than 0.04 ml / kg / min or administration of 5% IVIg solutions.