mlodipine besilate for 30 days at a dose comparable with the human dose based on mg/kg, decreased plasma follicle-stimulating hormone and testosterone were found as well as decreases in sperm density and in the number of mature spermatids and Sertoli cells.
Carcinogenesis, mutagenesis
Rats and mice treated with amlodipine in the diet for two years, at concentrations calculated to provide daily dosage levels of 0.5, 1.25, and 2.5 mg/kg/day showed no evidence of carcinogenicity. The highest dose (for mice, similar to, and for rats twice* the maximum recommended clinical dose of 10 mg on a mg/m2 basis) was close to the maximum tolerated dose for mice but not for rats.
Mutagenicity studies revealed no drug related effects at either the gene or chromosome levels.
*Based on patient weight of 50 kg
6. Pharmaceutical particulars
6.1 List of excipients
Tablet core:
Starch, pregelatinised maize
Silicified microcrystalline cellulose (microcrystalline cellulose with colloidal silicon dioxide)
Croscarmellose sodium
Magnesium stearate
Tablet coat:
Polyvinyl alcohol
Macrogol 3350
Talc
Titanium dioxide (E171)
Iron (III) oxide yellow (E172) (Sevikar 40 mg/ 5 mg and 40 mg/10 mg film-coated tablets only)
Iron (III) oxide red (E172) (Sevikar 40 mg/ 10 mg film-coated tablets only)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
5 years.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
OPA/Aluminium / PVC / Aluminium blister.
Pack sizes: 14, 28, 30, 56, 90, 98, 10 x 28 and 10 x 30 film-coated tablets.
Pack sizes with perforated unit dose blisters: 10, 50 and 500 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
DAIICHI SANKYO UK Limited
Chalfont Park
Gerrards Cross
England
SL9 0GA
UK
8. Marketing authorisation number(s)
Sevikar 20 mg/5 mg film-coated tablet:
Sevikar 40 mg/5 mg film-coated tablet:
Sevikar 40 mg/10 mg film-coated tablet:
PL 08265/0026
PL 08265/0027
PL 08265/0028
9. Date of first authorisation/renewal of the authorisation
29 October 2008/12 July 2013
10. Date of revision of the text
07/2017
https://www.medicines.org.uk/emc/medicine/21656 |
