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Zevalin is a brand name for Ibritumomab Tiuxetan. The medicine, its uses, side effects and dosage are the same regardless of brand.
Used for: Zevalin is indicated in adults. [90Y]-radiolabelled Zevalin is indicated as consolidation therapy after remission induction in previously untreated patients with follicular lymphoma. The benefit of Zevalin following rituximab in combination with chemotherapy has not been established. [90Y]-radiolabelled Zevalin is…
Verbatim from this product's EMA label. Tap a section to expand.
6 and 12). Posology Zevalin must be used following pretreatment with rituximab. Please refer to the Summary of Product Characteristics of rituximab for detailed guidance on its use. The treatment regimen consists of two intravenous administrations of rituximab and one administration of [90Y]-radiolabelled Zevalin solution in the following order: Day 1: intravenous infusion of 250 mg/m2 rituximab.
Day 7 or 8 or 9: - intravenous infusion of 250 mg/m2 rituximab shortly (within 4 hours) before administration of [90Y]-radiolabelled Zevalin solution. - 10-minute intravenous infusion of [90Y]-radiolabelled Zevalin solution.
Repeated use:
Data on the re-treatment of patients with Zevalin are not available.
The recommended radioactivity dose of [90Y]-radiolabelled Zevalin solution is:
Treatment of rituximab relapsed or refractory CD20+ follicular B-cell non-Hodgkin's lymphoma (NHL): - patients with ≥ 150,000 platelets/mm3: 15 MBq/kg body weight. - patients with 100,000-150,000 platelets/mm3: 11 MBq/kg The maximum dose must not exceed 1200 MBq.
Repeated use:
Data on the re-treatment of patients with [90Y]-radiolabeled Zevalin are not available. 4’ Repeated use: Data on the re-treatment of patients with [90Y]-radiolabelled Zevalin are not available. Special populations Paediatric population Zevalin is not recommended for use in children and adolescents below 18 years due to a lack of data on safety and efficacy.
Older people Limited data in elderly patients (aged ≥ 65 years) are available. No overall differences in safety or efficacy were observed between these patients and younger patients. Medicinal product no longer authorised 4 Patients with hepatic impairment The safety and efficacy have not been studied in patients with hepatic impairment.
Patients with renal impairment The safety and efficacy have not been studied in patients with renal impairment. Method of administration The [90Y]-radiolabelled Zevalin solution must be prepared according to section 12. Before administration to the patient, the percent radioincorporation of the prepared [90Y]-radiolabelled Zevalin must be checked according to the procedure outlined in section 12.
Exposure to ionising radiation is linked with cancer induction and a potential for development of hereditary defects. In all cases it is necessary to ensure that the risks of the radiation are less than from the disease itself. 2), see also the prescribing information of rituximab.
The overall safety profile of Zevalin after pretreatment with rituximab is based on data from 349 patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma studied in five clinical trials, on data from a study with 204 patients receiving Zevalin as consolidation therapy after first-line remission induction, and from post-marketing surveillance.
The most frequently observed adverse drug reactions in patients receiving Zevalin after pretreatment with rituximab are thrombocytopenia, leukocytopenia, neutropenia, anaemia, infections, pyrexia, nausea, asthenia, rigors, petechiae, and fatigue.
The most serious adverse drug reactions in patients receiving Zevalin after pretreatment with rituximab are: Severe and prolonged cytopenias (see also ‘Special warnings and precautions for use’) Infections Haemorrhage while thrombocytopenic Severe mucocutaneous reactions (see also ‘Special warnings and precautions for use’) Myelodysplastic syndrome / acute myeloid leukaemia Medicinal product no longer authorised 8 Fatal outcomes have been reported for each of the following serious adverse drug reactions.
These reports originated either from clinical trials or from postmarking experience. Infection Sepsis Pneumonia Myelodysplastic syndrome / Acute myeloid leukaemia Anaemia Pancytopenia Haemorrhage while thrombocytopenic Intracranial haemorrhage while thrombocytopenic Mucocutaneous reactions, including Stevens-Johnson Syndrome The frequencies of the adverse drug reactions which were considered to be at least possibly related to Zevalin after pretreatment with rituximab are represented in the table below.
Since the Zevalin regimen includes rituximab, see also the Summary of Product Characteristics of rituximab. [90Y]-radiolabelled Zevalin solution must only be received, handled and administered by qualified personnel with the appropriate government authorization for the use and manipulation of radionuclides within a designated clinical setting.
Its receipt, preparation, use, transfer, storage, and disposal are subject to the regulations and/or appropriate authorisation/licences of the local competent official organisations. Radiopharmaceuticals must be prepared by the user in a manner which satisfies both radiation safety and pharmaceutical quality requirements.
Appropriate aseptic precautions must be taken, complying with the requirements of Good Manufacturing Practice of pharmaceuticals. 2 and 12’). [90Y]-radiolabelled Zevalin solution must not be administered to patients who are likely to develop life-threatening haematological toxicity signs.
Zevalin must not be administered in patients mentioned below, as safety and efficacy have not been established: - > 25% of the bone marrow infiltrated by lymphoma cells - prior external beam radiation affecting more than 25% of active bone marrow Medicinal product no longer authorised 5 - platelet counts <100,000/mm3 (monotherapy) and <150,000/mm3 (consolidation treatment) - neutrophil counts < 1,500/mm3 - prior bone marrow transplant or stem cell support Haematological toxicity Special caution is required with respect to bone marrow depletion.
8). Therefore, complete blood cell and platelet counts must be monitored following Zevalin treatment weekly until levels recover or as clinically indicated. 5). 5). Human anti-murine antibodies Patients who had received murine-derived proteins before Zevalin treatment must be tested for human anti-murine antibodies (HAMA).
Patients who have developed HAMAs may have allergic or hypersensitivity reactions when treated with Zevalin or other murine-derived proteins. After use of Zevalin, patients must generally be tested for HAMA before any further treatment with murine-derived proteins.
1. - Hypersensitivity to rituximab or to other murine-derived proteins. 6).
Not medical advice. Always read the patient information leaflet and follow your prescriber or pharmacist.
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If the average radiochemical purity is less than 95%, the preparation must not be administered. The prepared solution must be given as a slow intravenous infusion over 10 minutes. The infusion must not be administered as an intravenous bolus.
Zevalin may be infused directly by stopping the flow from an infusion bag and administering it directly into the line. 22 micron low protein-binding filter must be on line between the patient and the infusion port. 9%) solution for injection after the infusion of Zevalin.
These adverse drug reactions are based upon 349 patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma studied in 5 clinical trials. In addition, the adverse drug reactions marked with ** were observed in the study with 204 patients receiving Zevalin as consolidation therapy after first-line remission induction where indicated.
The adverse drug reactions identified only during post-marketing surveillance, and for which a frequency could not be estimated, are listed under “not known“. Adverse reactions listed below are classified according to frequency and System Organ Class (MedDRA).
Frequency groupings are defined according to the following convention: (very common ≥1/10, common ≥1/100 to <1/10, uncommon ≥ 1/1,000 to 1/100, rare: 1/10,000 to <1/1,000; very rare: <1/10,000). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Table 1:
Adverse drug reactions reported in clinical trials or during post-marketing surveillance in patients treated with Zevalin after pretreatment with rituximab System Organ Class (MedDRA) Very common Common Uncommon Rare Not known Infections and infestations Infection* Sepsis*, Pneumonia*, Urinary tract infection, Oral candidiasis Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour pain, Myelodysplastic syndrome/Acute myeloid leukaemia*, ** Meningioma Blood and lymphatic system disorders Thrombocytopenia, Leukocytopenia, Neutropenia, Anaemia* Febrile neutropenia, Pancytopenia*, Lymphocytopenia Immune system disorders Hypersensitivity reaction Metabolism and nutrition disorders Anorexia Medicinal product no longer authorised 9 System Organ Class (MedDRA) Very common Common Uncommon Rare Not known Psychiatric disorders Anxiety, Insomnia Nervous system disorders Dizziness, Headache Cardiac disorders Tachycardia Vascular disorders Petechiae** Haemorrhage while thrombocytopenic* Hypertension** Hypotension** Intracranial haemorrhage while thrombocyto- penic* Respiratory, thoracic, and mediastinal disorders Cough, Rhinitis Gastrointestinal disorders Nausea Vomiting, Abdominal pain, Diarrhoea, Dyspepsia, Throat irritation, Constipation Reproductive system and breast disorders Amenorrhea** Skin and subcutaneous tissue disorders Rash, Pruritus Mucocutaneous reaction (including Stevens Johnson Syndrome) * Musculoskeletal and connective tissue disorders Arthralgia, Myalgia, Back pain, Neck pain General disorders and administration site conditions Asthenia, Pyrexia, Rigors Fatigue** Pain, Flu-like symptoms, Malaise, Peripheral oedema, Sweating increased Extravasation with subsequent infusion site reactions, Damage to lymphoma- surrounding tissue and complications due to lymphoma swelling * fatal outcome has been observed ** has been observed in a study with 204 patients receiving Zevalin as consolidation after first-line remission induction The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
Blood and lymphatic system disorders Haematological toxicity has been very commonly observed in clinical trials, and is dose-limiting (see also section ‘Special warnings and precautions for use’). Median time to blood platelet and granulocyte nadirs were around 60 days after start of treatment.
In clinical trials with the indication of relapsed and refractory NHL, grade 3 or 4 thrombocytopenia was reported with median times to recovery of 13 and 21 days and grade 3 or 4 neutropenia with median times to recovery of 8 and 14 days.
Following Zevalin as consolidation Medicinal product no longer authorised 10 after first line remission induction the median times to recovery was 20 days and 35 days for grade 3 or 4 thrombocytopenia and 20 days and 28 days for grade 3 or 4 neutropenia.
Infections and infestations - Data from 349 patients with relapsed or refractory low-grade, follicular […]
Infusion reactions Infusion reactions may occur during or following Zevalin administration after pretreatment with Rituximab. 8). In case of a potential severe infusion reaction treatment must be stopped immediately. Hypersensitivity Hypersensitivity reactions following Zevalin administration are commonly observed.
8). In case of hypersensitivity reactions, Zevalin infusion must be stopped immediately. g. adrenaline, antihistamines and corticosteroids, must be available for immediate use in the event of an allergic reaction during administration of rituximab or Zevalin.
Severe mucocutaneous reactions Severe mucocutaneous reactions, including Stevens-Johnson Syndrome, some with fatal outcome, have been reported in association with Zevalin after pretreatment with rituximab. The onset of the reactions varied from days to months.
In patients experiencing a severe mucocutaneous reaction treatment must be discontinued. Contraception Long-term animal studies on the effect on fertility and reproductive function have not been performed. There is a potential risk that ionizing radiation by [90Y]-radiolabelled Zevalin could cause toxic effects on female and male gonads.
2). Medicinal product no longer authorised 6 Immunization The safety and efficacy of immunization with any vaccine, particularly live viral vaccines, following therapy with Zevalin have not been studied. 5). A potentially limited ability to generate a primary or anamnestic humoral response to any vaccine following Zevalin treatment has to be taken into consideration.
NHL with CNS involvement No data are available on patients with CNS-lymphoma as those patients were not included in clinical studies. The use of Zevalin is therefore not recommended in NHL patients with CNS involvement. Extravasation Close monitoring for evidence of extravasation during the injection of Zevalin is required in order to avoid radiation-associated tissue damage.
If any signs or symptoms of extravasation have occurred, the infusion must be immediately terminated and restarted in another vein. 8). Excipients […]