ostimplantation loss, foetal oedema, cleft palate/lip, dermal aplasia and kinked or rudimentary tail. In rabbits, cabozantinib produced foetal soft tissue changes (reduced spleen size, small or missing intermediate lung lobe) and increased foetal incidence of total malformations. NOAEL for embryo-foetal toxicity and teratogenic findings were below human clinical exposure levels at intended therapeutic dose.
Juvenile rats (comparable to a >2 year old pediatric population) administered cabozantinib showed increased WBC parameters, decreased haematopoiesis, pubescent/immature female reproductive system (without delayed vaginal opening), tooth abnormalities, reduced bone mineral content and density, liver pigmentation and lymph node lymphoid hyperplasia. Findings in uterus/ovaries and decreased haematopoiesis appeared to be transient, while effects on bone parameters and liver pigmentation were sustained. Juvenile rats (correlating to a <2 year pediatric population) showed similar treatment-related findings, but appeared to be more sensitive to cabozantinib-related toxicity at comparable dose levels.
6. Pharmaceutical particulars
6.1 List of excipients
Tablet content
Microcrystalline cellulose
Anhydrous lactose
Hydroxypropyl cellulose
Croscarmellose sodium
Colloidal anhydrous silica
Magnesium stearate
Film-coating
Hypromellose 2910
Titanium dioxide (E171)
Triacetin
Iron oxide yellow (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
PVC/PCTFE blister with push-through aluminum foil backing containing 7 film-coated tablets. Each carton contains 4 blisters with 28 film-coated tablets.
HDPE bottle with a polypropylene child-resistant closure and three silica gel dessicant canisters. Each bottle contains 30 film-coated tablets.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Ipsen Pharma
65 quai Georges Gorse
92100 Boulogne-Billancourt
France
8. Marketing authorisation number(s)
Cabometyx 20 mg film-coated tablets
EU/1/16/1136/001
EU/1/16/1136/002
Cabometyx 40 mg film-coated tablets
EU/1/16/1136/003
EU/1/16/1136/004
Cabometyx 60 mg film-coated tablets
EU/1/16/1136/005
EU/1/16/1136/006
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 9 September 2016
10. Date of revision of the text
23 August 2018
Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu.
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