ct of severe hepatic impairment (Child-Pugh Class C) on the pharmacokinetics of naloxegol was not eva luated. Use in patients with severe hepatic impairment is not recommended.
Paediatric population
The pharmacokinetics of naloxegol in the paediatric population has not been studied.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and fertility.
Embryo-foetal development studies were conducted in rats and rabbits. A potentially treatment-related increased incidence of the skeletal variant bipartite vertebral centrum and a single foetus with anorchism was seen at the highest dose tested in the rat embryo-foetal development study. A possible treatment-related foetal skeletal malformation of fused arches was noted at highest dose tested in the rabbit embryo-foetal development study, in the absence of maternal toxicity. In a separate pre- and post-natal development study in rats, body weights were lower for male pups following maternal administration at the high dose. All these effects were observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use.
Carcinogenicity studies of naloxegol were conducted in rats and mice. In male rats, a dose-related increase in Leydig cell adenomas and interstitial cell hyperplasia was observed at exposures considered sufficiently in excess of the maximum human exposure. The observed neoplastic changes are well known hormonal and centrally mediated effects in the rat which are not relevant for humans.
Studies in suckling rats have shown that naloxegol is excreted in the milk.
6. Pharmaceutical particulars
6.1 List of excipients
Tablet core
mannitol (E421)
cellulose microcrystalline (E460)
croscarmellose sodium (E468)
magnesium stearate (E470b)
propyl gallate (E310)
Tablet coat
hypromellose (E464)
titanium dioxide (E171)
macrogol (E1521)
iron oxide red (E172)
iron oxide black (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
4 years
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Alu/alu blister.
12.5 mg film-coated tablets
Pack sizes of 30 and 90 film-coated tablets in non-perforated blisters.
Pack sizes of 30 x 1 and 90 x 1 film-coated tablets in perforated unit dose blisters.
25 mg film-coated tablets
Pack sizes of 10, 30 and 90 film-coated tablets in non-perforated blisters.
Pack sizes of 10 x 1, 30 x 1, 90 x 1 and 100 x 1 film coated tablets in perforated unit dose blisters.
Not all pack sizes may be marketed.
6.6 Speial precautions for disposal and other handling
No special requirements for disposal. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7. Marketing authorisation holder
Kyowa Kirin Holdings B.V.
Bloemlaan 2
2132NP Hoofddorp
The Netherlands
8. Marketing authorisation number(s)
EU/1/14/962/001
EU/1/14/962/002
EU/1/14/962/003
EU/1/14/962/004
EU/1/14/962/005
EU/1/14/962/006
EU/1/14/962/007
EU/1/14/962/008
EU/1/14/962/009
EU/1/14/962/010
EU/1/14/962/011
9. Date of first authorisation/renewal of the authorisation
Date of first authorisation: 8 De |
