ng studies, the expanded access programmes, clinical pharmacology studies and exploratory studies in unapproved indications. Because these reactions are reported from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to imatinib exposure.
Table 2 Adverse reactions from post-marketing reports
Neoplasm benign, malignant and unspecified (including cysts and polyps)
Not known:
Tumour haemorrhage/tumour necrosis
Immune system disorders
Not known:
Anaphylactic shock
Nervous system disorders
Not known:
Cerebral oedema
Eye disorders
Not known:
Vitreous haemorrhage
Cardiac disorders
Not known:
Pericarditis, cardiac tamponade
Vascular disorders
Not known:
Thrombosis/embolism
Respiratory, thoracic and mediastinal disorders
Not known:
Acute respiratory failure1, interstitial lung disease
Gastrointestinal disorders
Not known:
Ileus/intestinal obstruction, gastrointestinal perforation, diverticulitis
Skin and subcutaneous tissue disorders
Not known:
Palmoplantar erythrodysesthesia syndrome
Not known:
Lichenoid keratosis, lichen planus
Not known:
Toxic epidermal necrolysis
Musculoskeletal and connective tissue disorders
Not known:
Avascular necrosis/hip necrosis
Not known:
Growth retardation in children
1 Fatal cases have been reported in patients with advanced disease, severe infections, severe neutropenia and other serious concomitant conditions.
Laboratory test abnormalities
Haematology
In CML, cytopenias, particularly neutropenia and thrombocytopenia, have been a consistent finding in all studies, with the suggestion of a higher frequency at high doses 750 mg (phase I study). However, the occurrence of cytopenias was also clearly dependent on the stage of the disease, the frequency of grade 3 or 4 neutropenias (ANC < 1.0 x 109/l) and thrombocytopenias (platelet count < 50 x 109/l) being between 4 and 6 times higher in blast crisis and accelerated phase (59–64% and 44–63% for neutropenia and thrombocytopenia, respectively) as compared to newly diagnosed patients in chronic phase CML (16.7% neutropenia and 8.9% thrombocytopenia). In newly diagnosed chronic phase CML grade 4 neutropenia (ANC < 0.5 x 109/l) and thrombocytopenia (platelet count < 10 x 109/l) were observed in 3.6% and < 1% of patients, respectively. The median duration of the neutropenic and thrombocytopenic episodes usually ranged from 2 to 3 weeks, and from 3 to 4 weeks, respectively. These events can usually be managed with either a reduction of the dose or an interruption of treatment with Glivec, but can in rare cases lead to permanent discontinuation of treatment. In paediatric CML patients the most frequent toxicities observed were grade 3 or 4 cytopenias involving neutropenia, thrombocytopenia and anaemia. These generally occur within the first several months of therapy.
In the study in patients with unresectable and/or metastatic GIST, grade 3 and 4 anaemia was reported in 5.4% and 0.7% of patients, respectively, and may have been related to gastrointestinal or intra-tumoural bleeding in at least some of these patients. Grade 3 and 4 neutropenia was seen in 7.5% and 2.7% of patients, respectively, and grade 3 thrombocytopen |
