c acid (M6), plus two unknown metabolites. The remainder of the dose was recovered in faeces.
Gender: Adjusted for body mass and height, there are no significant gender differences in pharmacokinetic parameters following a single 20mg dose of rabeprazole.
Renal dysfunction: In patients with stable, end-stage, renal failure requiring maintenance haemodialysis (creatinine clearance ≤5ml/min/1.73m2), the disposition of rabeprazole was very similar to that in healthy volunteers. The AUC and the Cmax in these patients was about 35% lower than the corresponding parameters in healthy volunteers. The mean half-life of rabeprazole was 0.82 hours in healthy volunteers, 0.95 hours in patients during haemodialysis and 3.6 hours post dialysis. The clearance of the drug in patients with renal disease requiring maintenance haemodialysis was approximately twice that in healthy volunteers.
Hepatic dysfunction: Following a single 20mg dose of rabeprazole to patients with chronic mild to moderate hepatic impairment the AUC doubled and there was a 2-3 fold increase in half-life of rabeprazole compared to the healthy volunteers. However, following a 20mg dose daily for 7 days the AUC had increased to only 1.5-fold and the Cmax to only 1.2-fold. The half-life of rabeprazole in patients with hepatic impairment was 12.3 hours compared to 2.1 hours in healthy volunteers. The pharmacodynamic response (gastric pH control) in the two groups was clinically comparable.
Elderly: Elimination of rabeprazole was somewhat decreased in the elderly. Following 7 days of daily dosing with 20mg of rabeprazole sodium, the AUC approximately doubled, the Cmax increased by 60% and t? increased by approximately 30% as compared to young healthy volunteers. However there was no evidence of rabeprazole accumulation.
CYP2C19 Polymorphism: Following a 20mg daily dose of rabeprazole for 7 days, CYP2C19 slow metabolisers, had AUC and t? which were approximately 1.9 and 1.6 times the corresponding parameters in extensive metabolisers whilst Cmax had increased by only 40%.
5.3 Preclinical safety data
Non-clinical effects were observed only at exposures sufficiently in excess of the maximum human exposure that make concerns for human safety negligible in respect of animal data.
Studies on mutagenicity gave equivocal results. Tests in mouse lymphoma cell line were positive, but in vivo micronucleus and in vivo and in vitro DNA repair tests were negative. Carcinogenicity studies revealed no special hazard for humans.
6. Pharmaceutical particulars
6.1 List of excipients
Core tablet: Mannitol, magnesium oxide, low-substituted hyprolose, hyprolose, magnesium stearate
Undercoating: ethylcellulose, magnesium oxide
Enteric coating: hypromellose phthalate, diacetylated monoglycerides, talc, titanium dioxide (E171), red iron oxide (E172) – 10mg only, yellow iron oxide (E172) – 20mg only, carnauba wax
Printing ink – Pariet 10mg: White Shellac, black iron oxide (E172), Dehydrated Ethyl Alcohol, 1-Butanol.
Printing ink – Pariet 20mg: White Shellac, Red Iron Oxide (E172), Carnauba wax, Glycerine fatty acid ester, Dehydrated Ethyl Alcohol, 1-Butanol.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Do not store above 25°C. Do not refrigerate
6.5 Nature and contents of container
Blister strips (aluminium/aluminium)
Pack sizes: 1,5, 7, 14, 15, 25, 28, 30, |
