ects included exencephaly or encephalocele, absent/reduced frontal and absent parietal bones. These effects were not seen at doses 30 mg/kg.
In the 2-year rat carcinogenicity study administration of imatinib at 15, 30 and 60 mg/kg/day resulted in a statistically significant reduction in the longevity of males at 60 mg/kg/day and females at 30 mg/kg/day. Histopathological examination of decedents revealed cardiomyopathy (both sexes), chronic progressive nephropathy (females) and preputial gland papilloma as principal causes of death or reasons for sacrifice. Target organs for neoplastic changes were the kidneys, urinary bladder, urethra, preputial and clitoral gland, small intestine, parathyroid glands, adrenal glands and non-glandular stomach.
Papilloma/carcinoma of the preputial/clitoral gland were noted from 30 mg/kg/day onwards, representing approximately 0.5 or 0.3 times the human daily exposure (based on AUC) at 400 mg/day or 800 mg/day, respectively, and 0.4 times the daily exposure in children (based on AUC) at 340 mg/m2/day. The no observed effect level (NOEL) was 15 mg/kg/day. The renal adenoma/carcinoma, the urinary bladder and urethra papilloma, the small intestine adenocarcinomas, the parathyroid glands adenomas, the benign and malignant medullary tumours of the adrenal glands and the non-glandular stomach papillomas/carcinomas were noted at 60 mg/kg/day, representing approximately 1.7 or 1 times the human daily exposure (based on AUC) at 400 mg/day or 800 mg/day, respectively, and 1.2 times the daily exposure in children (based on AUC) at 340 mg/m2/day. The no observed effect level (NOEL) was 30 mg/kg/day.
The mechanism and relevance of these findings in the rat carcinogenicity study for humans are not yet clarified.
Non-neoplastic lesions not identified in earlier preclinical studies were the cardiovascular system, pancreas, endocrine organs and teeth. The most important changes included cardiac hypertrophy and dilatation, leading to signs of cardiac insufficiency in some animals.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core:
Cellulose microcrystalline
Crospovidone
Hypromellose
Magnesium stearate
Silica, colloidal anhydrous
Tablet coat:
Iron oxide, red (E172)
Iron oxide, yellow (E172)
Macrogol
Talc
Hypromellose
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
6.4 Special precautions for storage
Do not store above 30°C.
Store in the original package in order to protect from moisture.
6.5 Nature and contents of container
PVC/alu blisters
Packs containing 20, 60, 120 or 180 film-coated tablets
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
No special requirements.
7. MARKETING AUTHORISATION HOLDER
Novartis Europharm Limited
Wimblehurst Road
Horsham
West Sussex, RH12 5AB
United Kingdom
8. MARKETING AUTHORISATION NUMBER(S)
EU/1/01/198/007
EU/1/01/198/008
EU/1/01/198/011
EU/1/01/198/012
EU/1/01/198/009
EU/1/01/198/010
EU/1/01/198/013
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 11.11.2003
Date of first renewal: 07.11.2006
10. DATE OF REVISION OF THE TEXT
April 2011
Detailed information on this product is available on the website of the European Medici |
