Sofosbuvir was not genotoxic in a battery of in vitro or in vivo assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes and in vivo mouse micronucleus assays.

Carcinogenicity studies in mice and rats do not indicate any carcinogenicity potential of sofosbuvir administered at doses up to 600 mg/kg/day in mouse and 750 mg/kg/day in rat. Exposure to GS-331007 in these studies was up to 30 times (mouse) and 15 times (rat) higher than the clinical exposure at 400 mg sofosbuvir.

Sofosbuvir had no effects on embryo-foetal viability or on fertility in rat and was not teratogenic in rat and rabbit development studies. No adverse effects on behaviour, reproduction or development of offspring in rat were reported. In rabbit studies exposure to sofosbuvir was 9 times the expected clinical exposure. In the rat studies, exposure to sofosbuvir could not be determined but exposure margins based on the major human metabolite ranged from 8 to 28 times higher than the clinical exposure at 400 mg sofosbuvir.

Sofosbuvir-derived material was transferred through the placenta in pregnant rats and into the milk of lactating rats.
6. Pharmaceutical particulars
  
6.1 List of excipients
 Tablet core

Mannitol (E421)

Microcrystalline cellulose (E460(i))

Croscarmellose sodium

Colloidal anhydrous silica (E551)

Magnesium stearate (E470b)

Film-coating

Polyvinyl alcohol (E1203)

Titanium dioxide (E171)

Macrogol 3350 (E1521)

Talc (E553b)

Yellow iron oxide (E172)
6.2 Incompatibilities
 Not applicable.
6.3 Shelf life
 2 years.
6.4 Special precautions for storage
 This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
 Sovaldi tablets are supplied in high density polyethylene (HDPE) bottles with a polypropylene child-resistant closure containing 28 film-coated tablets with a silica gel desiccant and polyester coil.

The following pack sizes are available: outer cartons containing 1 bottle of 28 film-coated tablets and outer cartons containing 84 (3 bottles of 28) 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
 Gilead Sciences International Ltd.

Cambridge

CB21 6GT

United Kingdom
8. Marketing authorisation number(s)
 EU/1/13/894/001

EU/1/13/894/002
9. Date of first authorisation/renewal of the authorisation
 Date of first authorisation: 16 January 2014
10. Date of revision of the text
 Detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu