volunteers (matched by age, sex and weight). Caution should be exercised in patients with liver disease (see section 4.2).
5.3 Preclinical safety data
In a variety of preclinical safety studies conducted in several animal species with amlodipine, valsartan, hydrochlorothiazide, valsartan/hydrochlorothiazide, amlodipine/valsartan and amlodipine/valsartan/hydrochlorothiazide (Exforge HCT), there was no evidence of systemic or target organ toxicity that would adversely affect the development of Exforge HCT for clinical use in humans.
Preclinical safety studies of up to 13 weeks in duration were conducted with amlodipine/valsartan/hydrochlorothiazide in rats. The combination resulted in expected reduction of red blood cell mass (erythrocytes, haemoglobin, haematocrit, and reticulocytes), increase in serum urea, increase in serum creatinine, increase in serum potassium, juxtaglomerular (JG) hyperplasia in the kidney and focal erosions in the glandular stomach in rats. All these changes were reversible after a 4-week recovery period and were considered to be exaggerated pharmacological effects.
The amlodipine/valsartan/hydrochlorothiazide combination was not tested for genotoxicity or carcinogenicity as there was no evidence of any interaction between these substances, which have been on the market for a long time. However, amlodipine, valsartan and hydrochlorothiazide have been tested individually for genotoxicity and carcinogenicity with negative results.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core
Cellulose microcrystalline
Crospovidone
Silica, colloidal anhydrous
Magnesium stearate
Coating
Hypromellose
Macrogol 4000
Talc
Titanium dioxide (E171)
Iron oxide, yellow (E172)
Iron oxide, red (E172)
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
2 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/PVDC blisters. One blister contains 7, 10 or 14 film-coated tablets.
Pack sizes: 14, 28, 30, 56, 90, 98 or 280 film-coated tablets.
Multipacks of 280 tablets, comprising 20 cartons, each containing 14 tablets.
PVC/PVDC perforated unit dose blisters for hospital use:
Pack sizes: 56, 98 or 280 film-coated tablets
Multipacks of 280 tablets, comprising 4 cartons, each containing 70 tablets.
Not all pack sizes or strengths 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/1/09/569/013-024
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
16.10.2009
10. DATE OF REVISION OF THE TEXT
24.03.2011 |
