3 years.
None.
Content
Butylhydroxyanisole
Butylhydroxytoluene
Medium-chain triglycerides
Shell
Gelatin
Glycerol
Karion 83 (Sorbitol, Mannitol, Hydrogenated hydrolysed starch)
Titanium dioxide E171
Iron oxide red E172
Iron oxide yellow E172
Subchronic toxicity studies in rats and dogs indicated that calcitriol at an oral dose of 20 ng/kg/day (twice the usual human dosage) for up to 6 months produced no or minimal adverse effects. A dose of 80 ng/kg/day (8 times the usual human dosage) for up to 6 months produced moderate adverse effects; changes seen appeared to be primarily the result of prolonged hypercalcaemia.
Reproductive toxicity studies in rats indicated that oral doses up to 300 ng/kg/day (30 times the usual human dose) did not adversely affect reproduction. In rabbits, multiple foetal abnormalities were observed in two litters at an oral maternally toxic dose of 300 ng/kg/day and one litter at 80 ng/kg/day, but not at 20 ng/kg/day (twice the usual human dose). Although there were no statistically significant differences between treated groups and controls in the numbers of litters or foetuses showing abnormalities, the possibility that these findings were due to calcitriol administration could not be discounted.
Absorption
Calcitriol is rapidly absorbed from the intestine. Peak serum concentrations following a single oral dose of 0.25-1µg Rocaltrol in healthy subjects were found within 2-6 hours.
After a single oral dose of 0.5 mcg Rocaltrol in healthy subjects, the average serum concentrations of calcitriol rose from a baseline value of 40.0 ± 4.4 pg/ml to 60.0 ± 4.4 pg/ml after two hours, and then fell to 53.0 ± 6.9 after four hours, to 50.0 ± 7.0 after eight hours, to 44 ± 4.6 after twelve hours and to 41.5 ± 5.1 pg/ml after 24 hours.
Distribution
During transport in the blood at physiological concentrations, calcitriol is mostly bound to a specific vitamin D binding protein (DBP), but also, to a lesser degree, to lipoproteins and albumin. At higher blood calcitriol concentrations, DBP appears to become saturated, and increased binding to lipoproteins and albumin occurs.
Metabolism
Calcitriol is hydroxylated and oxidised in the kidney and in the liver by a specific cytochrome P450 enzyme: CYP24A1.
Several metabolites with different degrees of vitamin D activity have been identified.
Elimination
The elimination half-life of calcitriol in plasma ranges between 5 to 8 hours. However, the pharmacological effect of a single dose of calcitriol lasts at least 4 days. The elimination and absorption kinetics of calcitriol remain linear in a very broad dose range and up to 165 µg single oral dose. Calcitriol is excreted in the bile and may undergo an enterohepatic circulation.
24 June 2014
Roche Products Limited
6 Falcon Way
Shire Park
Welwyn Garden City
AL7 1TW
United Kingdom.
Do not store above 25°C. Store in the original package and keep the blisters in the outer carton in order to protect from light and moisture.
PVC opaque blisters containing 100 capsules (5 strips of 20 capsules).
Rocaltrol 0.25 microgram Capsules: PL 00031/0122
Rocaltrol 0.5 microgram Capsules: PL 00031/0123
Not applicable.
13 January 2003
