Index of drugs

Replacement therapy in adults and children and adolescents (0-18 years): in primary immunodeficiency syndromes with impaired antibody production; in hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukemia, in whom antibiotic prophylaxis was ineffective; in hypogammaglobulinaemia and recurrent bacterial infections in patients in the plateau phase of multiple myeloma who did not respond to pneumococcal immunization; in hypogammaglobulinemia in allogeneic stem cell transplant patients (HSCT); in patients with congenital AIDS with recurrent bacterial infections. Immunomodulatory treatment in adults and children and adolescents (0-18 years): in primary immune thrombocytopenia (ITP) in patients at high risk of bleeding or before surgery to increase platelet count; in the Guillain-Barre syndrome; in chronic demyelinating inflammatory polyneuropathy (CIDP); in Kawasaki disease.

1 ml contains 50 mg of human normal immunoglobulin (including at least 95% of immunoglobulin G). Distribution of IgG subclasses (mean values): IgG1 - 62.1%, IgG2 - 34.8% IgG3 - 2.5% IgG4 - 0.6%. The maximum IgA content is 50 μg / ml. The product contains maltose (100 mg / ml). The product contains 3 mmol / l (69 mg) of sodium.

Normal human immunoglobulin contains mainly immunoglobulin G (IgG) with a broad spectrum of antibodies against infectious agents. It contains IgG antibodies present in the normal population. It is usually prepared from a pool of plasma from at least 1000 donors. Decomposition of IgG subclasses is proportional to the distribution in human plasma. Appropriate doses allow the concentration of immunoglobulin G to be increased to normal values. The bioavailability in the recipient's circulation after intravenous administration is immediate and complete. Distribution between plasma and extravascular fluid occurs relatively quickly, after about 3-5 days a balance between intra- and extravascular space is achieved. T_0,5 is about 21 days (may vary in patients, especially those with primary immune deficiency syndromes). IgG and IgG complexes are broken down in cells of the reticuloendothelial system.

Hypersensitivity to the active substance or to any of the excipients. Hypersensitivity to human immunoglobulins, especially in patients with anti-IgA antibodies.

The preparation contains maltose (100 mg / ml) - some types of blood Glucose tests (eg using methods based on glucose dehydrogenase-pyrroloquinolinequinone (GDH-PQQ) or glucose-dye oxidoreductase) falsely interpret maltose (100 mg / ml) contained in preparation as glucose. This may result in a falsely high glucose reading during the infusion and for about 15 hours after the end of the infusion, which may lead to improper insulin delivery leading to life-threatening hypoglycaemia. In addition, cases of actual hypoglycaemia may remain untreated if the hypoglycaemic state has been masked by falsely elevated glucose readings. The blood glucose should be measured using the glucose-specific method (please check if the blood glucose test can be used with maltose-containing parenteral products). Some side effects may appear more often: in the case of too fast infusion; in patients who receive human normal immunoglobulin for the first time, or in rare cases when the human normal immunoglobulin preparation changes to another or when the preparation is given after a longer break. Potential complications can often be avoided by making sure that patients: are not allergic to human normal immunoglobulin, by the initial slow administration of the preparation (administration rate 0.46-0.92 ml / kg / h); they are closely monitored during infusion on side effects (especially patients receiving the formulation for the first time, patients who have previously received another IVIg formulation or in the case of a long break from the previous infusion should be monitored during the first infusion and for the first hour after the first infusion; they should be observed for at least 20 minutes after infusion). In the case of an adverse reaction, either the rate of administration should be reduced or the administration of immunoglobulins should be discontinued. In the event of a shock, follow the current medical standards for the treatment of shock.In all patients, intravenous Ig administration requires: appropriate hydration prior to commencement of Ig infusion, monitoring of urine output, monitoring of serum creatinine level, avoidance of concomitant use of loop diuretics. IVIg is not indicated in patients with selective IgA deficiency, in which IgA deficiency is the only major disorder. Due to the increased risk of thromboembolic events (myocardial infarction, cerebrovascular episode (including stroke), pulmonary artery thrombosis, deep vein thrombosis), caution should be exercised in prescribing and administering IVIg to obese patients and patients at risk for thrombotic conditions (older age, hypertension, diabetes mellitus and vascular diseases or a history of thrombotic events, acquired or congenital coagulation disorders, long-term immobilization, severe hypovolemia, diseases manifesting in increased blood viscosity). In patients at risk of adverse thromboembolic reactions, the product should be administered at the minimum infusion rate and at the lowest possible dose. There is a risk of acute renal failure in patients treated with intravenous immunoglobulin (especially in patients with risk factors such as pre-existing renal failure, diabetes, severe circulating blood volume reduction, overweight, concomitant use with nephrotoxic or age over 65 years). In the case of impaired renal function, interruption of intravenous Ig administration should be considered. Reports of impaired renal function and acute renal failure related to the use of preparations containing various excipients such as sucrose, glucose and maltose. In the overall number of cases, the proportion of products containing sucrose as a stabilizer was disproportionately larger. In patients at risk, intravenous immunoglobulin preparations without these excipients may be considered. In patients at risk of acute renal failure, intravenous immunoglobulins should be administered at the minimum infusion rate and at the lowest possible dose. During treatment with intravenous immunoglobulins, the syndrome of aseptic meningitis (AMS) has been reported. Discontinuation of IVIg treatment resulted in remission of AMS within a few days without any sequelae. The team usually starts within a few hours to 2 days from the IVIg application. Cerebrospinal fluid often reports pleocytosis up to several thousand cells per mm³, mainly granulocytes, and protein concentrations increased to several hundred mg / dl. AMS may be more frequent due to treatment with high doses of IVIg (2 g / kg). Patients receiving intravenous immunoglobulin should be monitored for clinical signs of haemolysis. Despite the use of standard anti-infective agents, the possibility of transmission of infectious agents by a preparation prepared from human blood or plasma can not be completely ruled out. This also applies to unknown or recently known viruses and other pathogens. It is believed that the preventive measures taken are effective against enveloped viruses such as HIV, HBV and HCV, and to non-enveloped viruses such as HAV. These agents may have limited efficacy against non-enveloped viruses, such as parvovirus B19. Based on the current clinical experience, immunoglobulin preparations do not carry the hepatitis A virus or parvovirus B19 and it is also assumed that the antibodies contained have a significant contribution to the protection against virus infections. No special recommendations for preventive measures or monitoring in children and adolescents.

The preparation should be used with caution in pregnant women and nursing mothers. IVIg preparations have been shown to cross the placenta, with severity during the third trimester. Clinical experience with the use of immunoglobulins suggests that no harmful effects on pregnancy, on the fetus or on the newborn are expected. Immunoglobulins are excreted in milk and may contribute to protecting the newborn from infections passing through mucous membranes.

Uncommon: headache. Very rare: dizziness, hypotension, acute renal failure, aseptic meningitis, haemolysis, skin reactions, joint pain, back pain, fever, chills, vomiting, nausea.Not known: pulmonary embolism, cerebrovascular accident, myocardial infarction, deep vein thrombosis, embolism, anaphylactic shock, hypersensitivity, haemolytic anemia, hypotension, elevated blood creatinine.

Intravenously. Replacement therapy must be initiated and monitored by a specialist physician experienced in the treatment of immunodeficiency. In substitution treatment, the dosage should be individual for each patient depending on the pharmacokinetic and clinical response. The following dosage methods are given as a guide.Substitution therapy in primary immunodeficiency syndromes. Dosage should be adjusted to achieve IgG levels (measured before the Next infusion), at least 5-6 g / l. From the start of treatment, 3 to 6 months is needed to compensate for the concentration. An initial dose of 0.4-0.8 g / kg given once is recommended, followed by administration of at least 0.2 g / kg every 3-4 weeks. achieve a concentration of 5-6 g / l in the circulating blood is 0.2-0.8 g / kg / month. After reaching a stable state, the intervals between infusions are 3-4 weeks. The level of immunoglobulin should be determined and assessed in relation to the incidence of infections. In order to reduce the incidence of infections, it may be necessary to increase the dose to obtain a higher concentration.Hypogammaglobulinaemia and recurrent bacterial infections in patients with chronic lymphocytic leukemia in whom antibiotic prophylaxis was ineffective; hypogammaglobulinaemia and recurrent bacterial infections in patients in the plateau phase of multiple myeloma who have not responded to pneumococcal immunizations; patients with congenital AIDS with recurrent bacterial infections. The recommended dose is 0.2-0.4 g / kg every 3-4 weeks.Hypogammaglobulinaemia in patients after allogeneic stem cell transplantation. The recommended dose is 0.2-0.4 g / kg every 3-4 weeks. A concentration above 5 g / l should be maintained.Primary immune thrombocytopenia. 2 alternative treatment regimens: 1. dose 0.8-1.0 g / kg on the first day; the dose can be repeated once in 3 days; 2. 0.4 g / kg a day for 2-5 days. Treatment can be repeated if the disease recurs.Guillain-Barre syndrome0.4 g / kg / day for more than 5 days.Chronic demyelinating inflammatory polyneuropathy (CIDP). Starting dose: 2 g / kg for 4 consecutive days; it is recommended to administer an initial dose every 3-4 weeks to achieve maximum therapeutic effect. Maintenance dose: the attending physician determines the maintenance dose; after achieving maximum effect, it is recommended to reduce the dosage and adjust the frequency of administration until the lowest therapeutic maintenance dose is obtained. It was shown that the initial dose was well tolerated for 7 consecutive therapeutic cycles conducted for over 6 months.Kawasaki disease. 1.6-2.0 g / kg in divided doses for 2-5 days or 2.0 g / kg as a single dose. Patients should receive Acetylsalicylic acid simultaneously. Dosing in children and adolescents (0-18 years) is not different from that used in adults. The experience in the use of intravenous immunoglobulins in children with chronic demyelinating inflammatory polyneuropathy (CIDP) is limited. However, published data are consistent and all show that IVIg treatment in adults and children is equally effective as in the case of previously approved indications.
Normal human immunoglobulin should be administered intravenously with an initial infusion rate of 0.46-0.92 ml / kg / h (10-20 drops / min) for 20-30 min. If well tolerated, the infusion rate can be gradually increased to a maximum of 1.85 ml / kg / h (40 drops / min).