 |
| Pariet |
J-2UU
Overdose En un est
Symptoms de edad
Experience to date wfth deilberate or accidental overdose is limited. The maximum established reaciona
exposure has not exceeded 60 mg twice daily, or 160 mg once daily. Effects are generally minimal, en el trat
representative of the known adverse event profile, and reversible without further medical inteNention. cautelosc
Treatment interacci
No spectic antidote is known. Rabeprazole sodium is extensively protein bound and is, therefore, Como oc
not readIy dialysable. As in any case of overdose, treatment should be symptomatic and general rabeprazc
supportive measures should be utilised. P450 (C
PHARMACOLOGICAL PROPERTIES menta mt
Pharmacodynamic properties fenitomna,
Mechanism ofAction El rabepr
Rabeprazole sodium beiongs to the class of anti-secretory compounds, the substituted benzimida- Puede oc
zoIS, that do not exhibit anticholinergic or H2 histamine antagonist properties, but suppress gastric vado una
acid secretion by the specific inhibition of the H’/K-ATPase enzyme (the acid or proton pump). The rabeprazc
effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespec- 22% de 1
tive of the stimulus. Animal studies indicate that after administration, rabeprazole sodium rapidly vigilar a
disappears from both the plasma and gastric mucosa. As a weak base, rabeprazole is rapidly mentos S
absorbed following all doses and is concentrated in the acid environment of the parietal cells. sirntilt
Rabeprazole is converted to the active suiphenamide form through protonation and it subsequently apreciaroi
reacts with the available cystenes on the proton pump. vancia clii
Mti-secretor/ Activity Estudios
After oral administration of a 20 mg dose of rabeprazole sodium the onset of the anti-secretory metaboliz
effect occurs within one hour, with the maximum effect occurring within two to four hours. Inhibition centracio
of basaL and fooa stimulated acid secretion 23 hours after the first dose of rabeprazole sodium are que los e
69% and 82% respectively and the duration of inhibition lasts up to 48 hours. The inhibitory effect cabe espi
of rabeprazole sodium on acid secretion increases slightly with repeated once-daily dosing, Embaraz
achieving steady state inhibition after three days. When the drug is discontinued, secretory activity No se dis
normalises over 2 to 3 days. Estudios
Helicobacter pylon is associated with acid peptic disease including duodenal ulcer (DU) and gastric fertilidad
ulcer (Gli). H. pylon is implicated as a major contributing factor in the development of gastritis and transferer
ulcers in such patients. Recent evidence also suggests a causative link between H. pylon and No se sat
gastric carcinoma. en rnujerE
Rabeprazole has been shown to nave a bactericidal effect on H. pylon in vitro. Eradication of cie Ia rata
H. pylon with Pariet (rabeprazole) and antimicrobiaJs is associated with high rates of healing of Efectos
mucosal lesions. Clinical experience from controlled randomised clinical trials indicate that rabepra- A tenor ci
zole 20 mg twice daily in combination with two antibiotics e.g. clarithromycin and amoxycillin or bable quE
clarithromycin and metronidazole (given at approved dose levels) for 1 week achieve >80% H. pylon disrninuy
eradication rate in paents with gastro-duodenal ulcers. As expected, there was a trend towards m
significantly tower eradication rates in patients with baseline metronidazole resistant H. pyloil iso- Efectos ii
lates and a trend towards the development of secondary resistance. Hence, local information on
the prevalence of resistance and local therapeutic guidelines should be taken in account in the En genera
efectos a
choice of an appropriate combination regimen for H. pylon eradication therapy. Further more, iii En estudi
patients with persistent infection, potential development of secondary resistance n patients with en cefale
primary susceptible strains) to an antibacterial agent should be taken into account in the considera- tis, dolor
tions for a new re-treatment regimen.
Serum Gastriri Effects mareos,
In clinical studies patients were treated once daily with 10 or 20 mg rabeprazole sodium, for up to (incidenci sia, nervi(
43 months duration. Serum gastrin levels increased during the first 2 to 8 weeks reflecting the jnfeccjofl( inhibitory effects on acid secretion and remained stable while treatment was continued. Gastrin En casos values returned to pre-treatment levels, usuafly within 1 to 2 weeks after discontinuation of therapy.
raciones
Human gastric biopsy specimens from the antrum and the fundus from over 500 patients receiving No obstai
rabeprazole or comparator treatment for up to 8 weeks have not detected changes in ECL cell hisy Ia sequ
tology, degree of gastritis, incidence of atrophic gastritis, intestinal metaplasia or distribution of Experienc
H. pylon infection. In over 250 patients followed for 35 months of continuous therapy, no significant Se han d
change in findings present at baseline was observed. tipo de e
Other Effects
suelen re
Systemic effects of rabeprazole sodium in the CNS, cardiovascular and respiratory systems have Se han ci
not been found to date, Rabeprazole sodium, given in oral doses of 20 mg for 2 weeks, had no ci
effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, o icterici
cortisol, oestrogen, testosterone, prolactin, cholecystokinin, secretin. glucagon, follicle stimulating Se han c
hormone (FSH), luteinising hormone (LH), renin, aldosterone or somatotrophic hormone. Necrôhsü
Pharmacokinetic properties Sobredo
Absorption S(ntoma
Pariet is an enteric-coated (gastro-resistant) tablet formulation of rabeprazole sodium. This presen- Hasta a
tation is necessary because rabeprazole is acid-labile. Absorption of rabeprazole therefore begins don m
only after the tablet leaves the stomach. Absorption is rapid. with peak plasma levels of rabeprazole Los efec
occurring approximately 3.5 hours after a 20 mg dose. Peak plasma concentrations (Cmv) of rabe- necesid
prazole and AUC are linear over the dose range of 10 mg to 40 mg. Absolute bioavailability of an Tratamie
oral 20 mg dose (compared to intravenous administration) is about 52% due in large part to pre- No se cc
systemic metabolism. Additionally the bioavailability does not appear to increase with repeat por 10 c
administration. In healthy subjects the plasma hall-life is approximately one hour (range 0.7 to ser sintc
1.5 hours), and the total body clearance is estimated to be 283 ± 98 mh’min. Neither food nor the PROPIE
time of day of administration of the treatment affect the absorption of rabeprazole sodium. Propied
Distribution
Mecani
Rabeprazole is approximately 97% bound to human plasma proteins. El rabe
Metabolism and excretion
tuidos,
In humans the thicether (Ml) and carboxylic acid (MG) are the main plasma metabolites with the tamina, sulphone (M2), desmethyl-thioether (M4) and mercapturic acid conjugate (M5) minor metabolites
enzima
observed at lower levels. Only the desmethyl metabolite (M3) has a small amount of anti-secretory voca Ia
activity, but it is not present in plasma. dos en
Following a single 20 mg C labelled oral dose of rabeprazole sodium, no unchanged drug was excreted in the urine. Approximately 90% of the dose was eliminated in urine mainly as the two rapidez
con raç
metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), plus two unknown El rabe
metabolites. The remainder of the dose was recovered in faeces.
dad re
Gender
Activid
Adjusted for body mass and height, there are no significant gender differences in pharmacokinetic Tras Ia
parameters following a single 20 mg dose of rabeprazole. - .
inicla e
Renal dysfunction
secreci
In patients with stable, end-stage, renal failure requiring maintenance haemodialysis (creatinine
clearance 5m1/mir,/1 .73mn2), the disposition of rabeprazole was very similar to that in healthy El efec
volunteers. The AUC and the Cm in these patients was about 35% lower than the corresponding Ia adm
parameters in healthy volunteers. The mean half-life of rabeprazole was 0.82 hours in healthy volun- duas. C
teers, 0.95 hours in patients during haemodialysis and 3.6 hours post dialysis. The clearance of the Helicoi
drug in patients with renal disease requiring maintenance haemodialysis was approximately twice
gastric
that in healthy volunteers. desarr
Hepatic dysfunction lOgico
FolLowing a single 20 mg dose of rabeprazole to patients with chronic mild to moderate hepatic Se ha
impairment the AUC doubled and there was a 2-3 told increase in half-life of rabeprazole compared
cacior
to the healthy volunteers. However, following a 20 mg dose daily for 7 days the AUG had increased de las
to only 1.5-fold and the Cm to only 1 .2-fold. The half-life of rabeprazole in patients with hepatic trolad’ impairment was 12.3 hours compared to 2.1 hours in healthy volunteers. The pharmacodynamnic
ejemp
response (gastric pH control) in the two groups was clinically comparable. adecL
Elderly
paciei
Elimination of rabeprazole was somewhat decreased in the elderly. Following 7 days of daily dosing erradi
with 20 mg of rabeprazole sodium, the AUC approximately doubled, the Cm increased by 60% tes al
and t increased by approximately 30% as compared to young healthy volunteers. However there gir el
was no evidence of rabeprazole-accumulation. tenen
CYP2C19 Polymorphism localE
Following a 20 mg daily dose of rabeprazole for 7 days, CYP2C19 stow metabolisers, had AUG and tratar
ty which were approximately 1.9 and 1.6 times the corresponding parameters in extensive metabo- caso users whilst C had increased by only 40%. Elect
Overdose En un est
Symptoms de edad
Experience to date wfth deilberate or accidental overdose is limited. The maximum established reaciona
exposure has not exceeded 60 mg twice daily, or 160 mg once daily. Effects are generally minimal, en el trat
representative of the known adverse event profile, and reversible without further medical inteNention. cautelosc
Treatment interacci
No spectic antidote is known. Rabeprazole sodium is extensively protein bound and is, therefore, Como oc
not readIy dialysable. As in any case of overdose, treatment should be symptomatic and general rabeprazc
supportive measures should be utilised. P450 (C
PHARMACOLOGICAL PROPERTIES menta mt
Pharmacodynamic properties fenitomna,
Mechanism ofAction El rabepr
Rabeprazole sodium beiongs to the class of anti-secretory compounds, the substituted benzimida- Puede oc
zoIS, that do not exhibit anticholinergic or H2 histamine antagonist properties, but suppress gastric vado una
acid secretion by the specific inhibition of the H’/K-ATPase enzyme (the acid or proton pump). The rabeprazc
effect is dose-related and leads to inhibition of both basal and stimulated acid secretion irrespec- 22% de 1
tive of the stimulus. Animal studies indicate that after administration, rabeprazole sodium rapidly vigilar a
disappears from both the plasma and gastric mucosa. As a weak base, rabeprazole is rapidly mentos S
absorbed following all doses and is concentrated in the acid environment of the parietal cells. sirntilt
Rabeprazole is converted to the active suiphenamide form through protonation and it subsequently apreciaroi
reacts with the available cystenes on the proton pump. vancia clii
Mti-secretor/ Activity Estudios
After oral administration of a 20 mg dose of rabeprazole sodium the onset of the anti-secretory metaboliz
effect occurs within one hour, with the maximum effect occurring within two to four hours. Inhibition centracio
of basaL and fooa stimulated acid secretion 23 hours after the first dose of rabeprazole sodium are que los e
69% and 82% respectively and the duration of inhibition lasts up to 48 hours. The inhibitory effect cabe espi
of rabeprazole sodium on acid secretion increases slightly with repeated once-daily dosing, Embaraz
achieving steady state inhibition after three days. When the drug is discontinued, secretory activity No se dis
normalises over 2 to 3 days. Estudios
Helicobacter pylon is associated with acid peptic disease including duodenal ulcer (DU) and gastric fertilidad
ulcer (Gli). H. pylon is implicated as a major contributing factor in the development of gastritis and transferer
ulcers in such patients. Recent evidence also suggests a causative link between H. pylon and No se sat
gastric carcinoma. en rnujerE
Rabeprazole has been shown to nave a bactericidal effect on H. pylon in vitro. Eradication of cie Ia rata
H. pylon with Pariet (rabeprazole) and antimicrobiaJs is associated with high rates of healing of Efectos
mucosal lesions. Clinical experience from controlled randomised clinical trials indicate that rabepra- A tenor ci
zole 20 mg twice daily in combination with two antibiotics e.g. clarithromycin and amoxycillin or bable quE
clarithromycin and metronidazole (given at approved dose levels) for 1 week achieve >80% H. pylon disrninuy
eradication rate in paents with gastro-duodenal ulcers. As expected, there was a trend towards m
significantly tower eradication rates in patients with baseline metronidazole resistant H. pyloil iso- Efectos ii
lates and a trend towards the development of secondary resistance. Hence, local information on
the prevalence of resistance and local therapeutic guidelines should be taken in account in the En genera
efectos a
choice of an appropriate combination regimen for H. pylon eradication therapy. Further more, iii En estudi
patients with persistent infection, potential development of secondary resistance n patients with en cefale
primary susceptible strains) to an antibacterial agent should be taken into account in the considera- tis, dolor
tions for a new re-treatment regimen.
Serum Gastriri Effects mareos,
In clinical studies patients were treated once daily with 10 or 20 mg rabeprazole sodium, for up to (incidenci sia, nervi(
43 months duration. Serum gastrin levels increased during the first 2 to 8 weeks reflecting the jnfeccjofl( inhibitory effects on acid secretion and remained stable while treatment was continued. Gastrin En casos values returned to pre-treatment levels, usuafly within 1 to 2 weeks after discontinuation of therapy.
raciones
Human gastric biopsy specimens from the antrum and the fundus from over 500 patients receiving No obstai
rabeprazole or comparator treatment for up to 8 weeks have not detected changes in ECL cell hisy Ia sequ
tology, degree of gastritis, incidence of atrophic gastritis, intestinal metaplasia or distribution of Experienc
H. pylon infection. In over 250 patients followed for 35 months of continuous therapy, no significant Se han d
change in findings present at baseline was observed. tipo de e
Other Effects
suelen re
Systemic effects of rabeprazole sodium in the CNS, cardiovascular and respiratory systems have Se han ci
not been found to date, Rabeprazole sodium, given in oral doses of 20 mg for 2 weeks, had no ci
effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone, o icterici
cortisol, oestrogen, testosterone, prolactin, cholecystokinin, secretin. glucagon, follicle stimulating Se han c
hormone (FSH), luteinising hormone (LH), renin, aldosterone or somatotrophic hormone. Necrôhsü
Pharmacokinetic properties Sobredo
Absorption S(ntoma
Pariet is an enteric-coated (gastro-resistant) tablet formulation of rabeprazole sodium. This presen- Hasta a
tation is necessary because rabeprazole is acid-labile. Absorption of rabeprazole therefore begins don m
only after the tablet leaves the stomach. Absorption is rapid. with peak plasma levels of rabeprazole Los efec
occurring approximately 3.5 hours after a 20 mg dose. Peak plasma concentrations (Cmv) of rabe- necesid
prazole and AUC are linear over the dose range of 10 mg to 40 mg. Absolute bioavailability of an Tratamie
oral 20 mg dose (compared to intravenous administration) is about 52% due in large part to pre- No se cc
systemic metabolism. Additionally the bioavailability does not appear to increase with repeat por 10 c
administration. In healthy subjects the plasma hall-life is approximately one hour (range 0.7 to ser sintc
1.5 hours), and the total body clearance is estimated to be 283 ± 98 mh’min. Neither food nor the PROPIE
time of day of administration of the treatment affect the absorption of rabeprazole sodium. Propied
Distribution
Mecani
Rabeprazole is approximately 97% bound to human plasma proteins. El rabe
Metabolism and excretion
tuidos,
In humans the thicether (Ml) and carboxylic acid (MG) are the main plasma metabolites with the tamina, sulphone (M2), desmethyl-thioether (M4) and mercapturic acid conjugate (M5) minor metabolites
enzima
observed at lower levels. Only the desmethyl metabolite (M3) has a small amount of anti-secretory voca Ia
activity, but it is not present in plasma. dos en
Following a single 20 mg C labelled oral dose of rabeprazole sodium, no unchanged drug was excreted in the urine. Approximately 90% of the dose was eliminated in urine mainly as the two rapidez
con raç
metabolites: a mercapturic acid conjugate (M5) and a carboxylic acid (M6), plus two unknown El rabe
metabolites. The remainder of the dose was recovered in faeces.
dad re
Gender
Activid
Adjusted for body mass and height, there are no significant gender differences in pharmacokinetic Tras Ia
parameters following a single 20 mg dose of rabeprazole. - .
inicla e
Renal dysfunction
secreci
In patients with stable, end-stage, renal failure requiring maintenance haemodialysis (creatinine
clearance 5m1/mir,/1 .73mn2), the disposition of rabeprazole was very similar to that in healthy El efec
volunteers. The AUC and the Cm in these patients was about 35% lower than the corresponding Ia adm
parameters in healthy volunteers. The mean half-life of rabeprazole was 0.82 hours in healthy volun- duas. C
teers, 0.95 hours in patients during haemodialysis and 3.6 hours post dialysis. The clearance of the Helicoi
drug in patients with renal disease requiring maintenance haemodialysis was approximately twice
gastric
that in healthy volunteers. desarr
Hepatic dysfunction lOgico
FolLowing a single 20 mg dose of rabeprazole to patients with chronic mild to moderate hepatic Se ha
impairment the AUC doubled and there was a 2-3 told increase in half-life of rabeprazole compared
cacior
to the healthy volunteers. However, following a 20 mg dose daily for 7 days the AUG had increased de las
to only 1.5-fold and the Cm to only 1 .2-fold. The half-life of rabeprazole in patients with hepatic trolad’ impairment was 12.3 hours compared to 2.1 hours in healthy volunteers. The pharmacodynamnic
ejemp
response (gastric pH control) in the two groups was clinically comparable. adecL
Elderly
paciei
Elimination of rabeprazole was somewhat decreased in the elderly. Following 7 days of daily dosing erradi
with 20 mg of rabeprazole sodium, the AUC approximately doubled, the Cm increased by 60% tes al
and t increased by approximately 30% as compared to young healthy volunteers. However there gir el
was no evidence of rabeprazole-accumulation. tenen
CYP2C19 Polymorphism localE
Following a 20 mg daily dose of rabeprazole for 7 days, CYP2C19 stow metabolisers, had AUG and tratar
ty which were approximately 1.9 and 1.6 times the corresponding parameters in extensive metabo- caso users whilst C had increased by only 40%. Elect
No comments:
Post a Comment