Index of drugs

Consolidation treatment, after induction of remission, previously untreated patients with follicular lymphoma. The benefits of using the product after treatment with rituximab in combination with chemotherapy have not been established. Treatment of adult patients with refractory CD20 + in the form of follicular B-cell non-Hodgkin's lymphoma or patients with relapse after treatment with rituximab.

1 vial contains 3.2 mg of ibritumomab tiuxetan. The preparation is supplied as a kit for the preparation of ibritumomab yttrium-90 tixetan. The finished preparation after radiolabelling contains 2.08 mg of ibritumomab tiuxetan in a total volume of 10 ml.

Recombinant mouse IgG monoclonal antibody₁ of the kappa type specific for CD20 B cell antigen. Ibrytumomab tiuxetan is directed against the CD20 antigen, which is located on the surface of normal and malignant B lymphocytes. Radiolabelled preparation [⁹⁰Y] binds specifically to B cells, including tumor cells expressing CD20 antigen. The yttrium-90 isotope is a pure beta particle emitter with an average impact range of about 5 mm. As a result, it has the ability to destroy both target cells and neighboring cells. Premedication with rituximab is necessary to remove circulating B cells, which will allow more precise irradiation of lymphoma cells through the preparation. Rituximab is administered at a lower dose compared to that approved alone. Treatment with a radionuclide [⁹⁰Y] also leads to a reduction in the number of normal CD20 + B cells. Pharmacodynamic analysis showed that this is a transient symptom. The formation of normal B cells begins within 6 months, and within 9 months after treatment, the median B cell count returns to normal values. In patients receiving 250 mg / m2 rituximab followed by intravenous administration of a radionuclide [⁹⁰Y] at a dose of 15 MBq / kg body weight, the median effective half-life of the radiolabelled formulation in the blood [⁹⁰Y] was 28 h. Because the yttrium-90 radioisotope forms a stable relationship with ibritumomab tiuxetan, biodistribution of the radiolar corresponds to the biodistribution of the antibody. The irradiation with beta molecules emitted by the yttrium-90 radioisotope occurs within a radius of 5 mm around the isotope. There is a risk that the isotope labeled preparation [⁹⁰Y] after previous treatment with rituximab may have an effect damaging female and male reproductive organs.

Hypersensitivity to ibritumomab tiuxetan, yttrium chloride, rituximab, other murine proteins or other components of the preparation. Pregnancy and breastfeeding.

It must not be used in patients who may develop life-threatening haematological toxicity. The preparation should not be administered to the below-mentioned groups of patients, as safety and efficacy have not been established: patients in whom bone marrow involvement with lymphoma cell infiltration is greater than 25%; patients who have received previous radiotherapy with an external beam of radiation including more than 25% of active bone marrow; patients receiving the monotherapy with platelet count <100,000 / mm³ and patients receiving the preparation for consolidation treatment, after induced remission, with platelet count <100,000 / mm³ and patients receiving the preparation for consolidation treatment, after induced remission, with platelet count <150,000 / mm³; patients with a neutrophil count <1,500 / mm³; patients who have previously had a bone marrow or stem cell transplant. It is not recommended: administration of live virus vaccines to patients who have recently received the preparation and use in patients with non-Hodgkin's lymphoma with an o.u.n. The preparation is not recommended for children and adolescents under 18 years of age. The patients should not receive growth factors, such as G-CSF, for 3 weeks before the start of the treatment and 2 weeks after the end of the therapeutic regimen.Special attention should be paid to the possibility of bone marrow damages. If the preparation is administered in less than 4 months after the last fludarabine treatment, its haematological toxicity may increase. Patients who experience mucosal skin reactions or hypersensitivity reactions during treatment should discontinue treatment. In the case of extravasation, the administration should be discontinued and resumed by administering the drug to another vein. During or after the preparation, premedication with rituximab may result in an infusion reaction (discontinuation of treatment). Treatment with the product may affect fertility. Ready solution of radiolabelled preparation [⁹⁰Y] contains less than 28 mg sodium per dose depending on the concentration of radioactivity, which should be taken into account in patients controlling the sodium content of the diet.

Animal reproductive capacity was not investigated when ibritumomab tiuxetan was used. Due to the observed phenomenon of permeation of IgG through the placenta and simultaneous use of radioactive substances, the preparation is contraindicated for use in pregnancy. Before starting treatment in women, pregnancy should be excluded. Women and men of child-bearing age should use effective contraception during treatment and for 12 months after treatment. It is not known whether ibritumomab tiuxetan is excreted in human milk. Due to the fact that IgG is excreted in human milk and because it is not known whether absorption and immunosuppression is possible in an infant, women must stop breast-feeding. The preparation is given after the initial administration of rituximab, therefore breast-feeding is not recommended for 12 months after treatment.

The dose of radiation associated with the therapeutic exposure may lead to the appearance of secondary forms of malignant tumors and the development of hereditary defects. It must be ensured that the risks associated with radiation are lower than the risks associated with the disease itself. Very common: parasitic infection, thrombocytopenia, leukocytopenia, neutropenia, anemia; petechiae; nausea; asthenia, fever, chills, fatigue. Common: sepsis, pneumonia, urinary tract infection, oral candidiasis; cancer pain, myeloblastic syndrome / acute myeloid leukemia; neutropenic fever, pancytopenia, lymphocytopenia; hypersensitivity reactions; lack of appetite; anxiety, insomnia; pain and dizziness; hemorrhage with thrombocytopenia, hypertension, hypotension; cough, rhinitis; vomiting, abdominal pain, diarrhea, indigestion, irritation of the throat, constipation; lack of menstruation; rash, pruritus; pain in the joints, muscle aches, back pain, neck pain; pain, flu-like symptoms, malaise, peripheral edema; increased sweating. Uncommon: tachycardia. Rare: meningioma; intracranial haemorrhage with thrombocytopenia. Not known: mucocutaneous reaction (including Stevens-Johnson syndrome); extravasation with reactions at the infusion site, damage to tissues surrounding lymphoma and complications caused by lymphoma edema. Deaths have been reported for the following adverse reactions: infection, sepsis, pneumonia, myelodysplastic syndrome / acute myeloid leukemia, anemia, pancytopenia, thrombocytopenia hemorrhage, cranial hemorrhage during thrombocytopenia and mucocutaneous reactions (including Stevens-Johnson).

The preparation should be used and administered only by qualified medical personnel, and its preparation must be carried out in accordance with the requirements in the field of radiological safety and pharmaceutical quality. The preparation should be used after previous treatment with rituximab (detailed information on the use of rituximab can be found in the product information). Treatment includes two intravenous administrations of rituximab and one administration of a radiolabelled preparation [⁹⁰Y] in the following order: day 1 - intravenous infusion of rituximab at a dose of 250 mg / m2; day 7, 8 or 9 - intravenous infusion of rituximab at a dose of 250 mg / m2 shortly (within 4 h) before administration of radiolabelled Zevalin [⁹⁰Y] in a 10-minute intravenous infusion. No data on repeated use of the preparation. The recommended dose of radioactivity of the radiolabelled preparation [⁹⁰Y] is:Treatment of patients with CD20 + refractory form of follicular B-cell non-Hodgkin's lymphoma or relapse patients after treatment with rituximab - patients with platelet count ≥ 150,000 plates / mm³: 15 MBq / kg body weight, patients with platelet count 100,000-150,000 plates / mm³: 11 MBq / kg The maximum dose can not exceed 1200 Mbq.Consolidation treatment, after induction of remission, previously untreated patients with follicular lymphoma - patients with a platelet count of ≥ 150,000 plates / mm³: 15 MBq / kg up to a maximum dose of 1200 MBq, patients with platelet count less than 150,000 plates / mm³. There were no general differences in the safety and efficacy between these patients and younger patients. The safety and efficacy of patients with impaired hepatic and renal function has not been studied. Method of administration: the solution prepared for infusion should be administered during a slow intravenous infusion over 10 min. Do not administer an intravenous bolus. The infusion of the preparation should be administered directly to the infusion set after stopping the fluid flow. An infusion filter between the patient and the infusion port should have a low protein binding filter with a density of 0.2 or 0.22 micron. After the infusion has been completed, the infusion set should be rinsed with at least 10 ml of 0.9% NaCl solution.