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 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.
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 Thrombocytop enia, Leukocytopeni a, Neutropenia, Anaemia* Febrile neutropenia, Pancytopenia*, Lymphocytopeni a Immune system disorders Hypersensitivity reaction Metabolism and nutrition disorders Anorexia Psychiatric disorders Anxiety, Insomnia System Organ Class (MedDRA) Very common Common Uncommon Rare Not known Nervous system disorders Dizziness, Headache Cardiac disorders Tachycardia Vascular disorders Petechiae** Haemorrhage while thrombocytopeni c* 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 Mucocutane ous reaction (including Stevens Johnson Syndrome) * Musculoskeletal and connective tissue disorders Arthralgia, Myalgia, Back pain, Neck pain System Organ Class (MedDRA) Very common Common Uncommon Rare Not known General disorders and administration site conditions Asthenia, Pyrexia, Rigors Fatigue** Pain, Flu-like symptoms, Malaise, Peripheral oedema, Sweating increased Extravasatio n with subsequent infusion site reactions, Damage to lymphoma- surrounding tissue and complicatio ns 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 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 lymphoma, or transformed non-Hodgkin’s lymphoma […]