Each coated tablet of Rabec® 10 mg contains:
Rabeprazole sodium 10 mg.
Inactive ingredients: mannitol 77.50 mg, heavy magnesium oxide 10 mg,
hydroxypropyl cellulose 2.4 mg, croscarmellose sodium 6.10 mg, talc 9.69
mg, magnesium stearate 1 mg, Eudragit L/100 12.2525 mg, polyethylene
glycol 6000 0.61 mg, yellow lacquer D&C Nº 10 0.15 mg, sunset yellow
lacquer Nº 6 0.009 mg, titanium dioxide 3.0633 mg, triethylcitrate 1.2252 mg.
Each coated tablet of Rabec® 20 mg contains:
Rabeprazole sodium 20 mg.
Inactive ingredients: mannitol 88.861 mg, heavy magnesium oxide 11.4644
mg, hydroxypropyl cellulose 3.0237 mg, croscarmellose sodium 7.6441 mg,
talc 13.4324 mg, magnesium stearate 1.2 mg, Eudragit L/100 12.2525 mg,
polyethylene glycol 6000 0.35 mg, yellow lacquer D&C Nº 10 0.176 mg,
sunset yellow lacquer D&C Nº 6 0.017 mg, titanium dioxide 1.3469 mg,
triethylcitrate 1.2252 mg.
Antiulcer. Inhibitor of gastric acid secretion.
Code ATC: A02BC04.
Rabec® tablets are indicated for:
Treatment of active duodenal ulcer and active benign gastric ulcer.
Treatment of erosive or ulcerative symptomatic gastroesophageal reflux
disease (GERD).
Maintenance treatment for GERD.
Treatment of moderate to severe symptomatic GERD.
Zollinger- Ellison syndrome.
Helicobacter pylori Eradication in patients with peptic ulcer, in combination
with appropriate antibiotic therapy.
Pharmacological action
Mechanism of Action: Rabeprazole belongs to a class of antisecretory
compounds (substituted benzimidazole) that do not exhibit anticholinergic
or histamine H2-receptor antagonist properties, but suppress gastric acid
secretion by inhibiting the gastric H+, K+ATPase (proton pump). The effect is
dose dependent and leads to inhibition of basal secretion and stimulated
acid secretion. Animal studies indicate that after administration, Rabeprazole
rapidly disappears from plasma and gastric mucosa. Being a weak base,
Rabeprazole is rapidly absorbed and is concentrated in the acidic
environment of the parietal cells. It is converted to its active sulfenamide form
through proton binding and subsequently interacts with the cysteines
available in the proton pump.
Antisecretory Activity: After oral administration of a dose of 20 mg of
rabeprazole onset of action occurs within the first hour, reaching maximum
effect within 2 to 4 hours. The inhibition of basal secretion and secretion
stimulated by food, 23 hours after the first dose of rabeprazole is 69% and
82% respectively. The inhibition lasts up to 48 hours. The inhibitory effect of
Rabeprazole on acid secretion increases slightly with once a day repeated
doses, reaching steady state after three days. After discontinuation of the
drug, secretory activity returns to normal after 2 to 3 days.
Effects on Serum Gastrin: In clinical studies patients were treated with a dose
of Rabeprazole 10 or 20 mg once daily for a period of up to 43 months of
treatment. Serum gastrin increased during the first 2 to 8 weeks reflecting the
inhibitory effect on acid secretion and remained stable during treatment.
Serum gastrin levels returned to pre-treatment, usually within the first or
second week after discontinuing it.
In biopsies of gastric antrum and fundus of more than 500 patients who
received Rabeprazole or other drug of the group for a period of up to 8 weeks,
there were no changes in the histology of Enterochromaffin-like (ECL) Cells,
grade of gastritis, incidence of atrophic gastritis, intestinal metaplasia or
infection distribution by H. Pylori. In over 250 patients followed for 36 months
of continuous treatment, there were no significant changes from baseline.
Other effects: No systemic effects of Rabeprazole were found in the central
nervous system, the cardiovascular system and the respiratory system.
Rabeprazole in doses of 20 mg orally for 2 weeks, had no effects on thyroid
function, metabolism of carbohydrates, or serum levels of parathyroid
hormone, cortisol, estrogen, testosterone, prolactin, cholecystokinin, secretin,
glucagon, follicle stimulating hormone (FSH), luteinizing hormone (LH),
renin, aldosterone or somatotrophic hormone.
Studies in healthy individuals have shown that Rabeprazole does not have
clinically significant interactions with amoxicillin or clarithromycin when
administered together for the eradication of H. pylori from the upper
gastrointestinal tract.
Absorption: Rabec® is a Rabeprazole sodium gastro-resistant coated tablet.
This formulation is necessary because Rabeprazole is acid labile.
Rabeprazole absorption begins after the tablet leaves the stomach. The
absorption is rapid with a plasma peak at about 3.5 hours after a dose of 20
mg. The rabeprazole Cmax and AUC (Area under the curve) have a linear
behavior within a dose range of 10 to 40 mg. The absolute bioavailability of
an oral dose of 20 mg (compared to intravenous administration) is
approximately 52% due in large part to its presystemic metabolism.
Bioavailability does not appear to increase with repeated administration. In
healthy individuals the plasma half-life is of approximately 1 hour (range 0.7
to 1.5 hours.), and the clearance is about 283 ± 98 ml / min. Neither food nor
time of day of administration has shown to affect the absorption of
Rabeprazole sodium.
Distribution: Rabeprazole is 97% bound to plasma proteins.
Metabolism and Elimination: Rabeprazole is metabolized by cytochrome
P450. In vitro studies using human liver microsomes indicated that
Rabeprazole sodium is metabolized by CYP2C19 and CYP3A4 isozymes. It
was found in these studies that rabeprazole does not induce or inhibit
CYP3A4. While in vitro studies do not predict the in vivo response, these
findings indicate that an interaction between Rabeprazole and cyclosporine
is not to be expected. In humans, thioether (M1) and carboxylic acid (M6) are
the main metabolites. Only the desmethyl metabolite (M3) has a mild
antisecretory activity, but it is not found in plasma.
Following a single 20 mg dose of 14C-labeled Rabeprazole, there was no
urinary excretion of unchanged drug. Approximately 90% of the dose was
excreted in urine mainly as carboxylic acid (M6) and mercapturic acid (M5)
metabolites, along with other metabolites. The rest of the dose is eliminated
through feces.
Features in special patient groups
Gender: After adjusting for body mass index and height, there are no
significant gender differences in pharmacokinetic parameters after a single
dose of rabeprazole 20 mg.
Renal impairment: In patients with renal failure requiring dialysis (with
creatinine clearance ≤ 5 ml/min/1.73m2), the disposition of rabeprazole was
similar to that found in healthy individuals. The AUC (Area under the curve)
and Cmax (maximum concentration) in these patients was 35% lower than in
healthy volunteers. The half-life was 0.82 hours in healthy volunteers, 0.95
hours during hemodialysis and 3.6 hours post dialysis. The clearance of the
drug in patients requiring hemodialysis was approximately twice that found
in healthy volunteers.
Hepatic impairment: Following administration of a single dose of 20 mg of
Rabeprazole to patients with chronic mild to moderate hepatic impairment,
the AUC and Cmax, doubled and half-life increased 2 to 3 times compared to
healthy volunteers. However, after a daily dose of 20 mg for 7 days, the AUC
increased 1.5 fold and Cmax 1.2-fold. The half-life of Rabeprazole in patients
with liver failure was 12.3 hours compared with 2.1 hours in healthy
volunteers. Pharmacodynamics’ response in both groups (Control of gastric
pH) was clinically comparable.
Elderly: The elimination of Rabeprazole was diminished in this age group.
After 7 days of administration of a daily dose of 20 mg of Rabeprazole
sodium, the AUC was almost doubled, Cmax increased by 60% and half-life
increased approximately 30% compared to young healthy volunteers. But
there was no evidence of accumulation of rabeprazole.
CYP2C19 polymorphism: After a daily dose of 20 mg for 7 days, poor
metabolizers had an AUC and half-life 1.9 and 1.6 times respectively higher
than the parameters for faster metabolizers, while the Cmax increased only 40%.
Rabec® tablets should be swallowed whole. The tablets should not be
chewed, or split.
Treatment of active duodenal ulcer and active benign gastric ulcer
The recommended dose for the treatment of both active duodenal ulcer and
of active benign gastric ulcer is 20 mg once daily in the morning.
Most active duodenal ulcer patients achieve resolution of symptoms within
four weeks of treatment. However, some patients may require four weeks of
treatment more to achieve healing. The majority of patients with active
benign gastric ulcer resolve their symptoms within six weeks of treatment.
However, some patients may also require an additional six weeks of treatment
to achieve healing.
Treatment of erosive or ulcerative gastroesophageal reflux disease (GERD)
The recommended dose for this disease is 20 mg once daily for four to eight
Maintenance in Treatment of erosive or ulcerative GERD
For long-term management, a maintenance dose of Rabec® 20 mg or 10 mg
once daily may be given taking into account the patient's response.
Treatment of symptomatic moderate to severe GERD
The recommended dose for patients without esophagitis is 10 mg once daily.
In case of failure to achieve control of symptoms after 4 weeks of treatment,
the patient should be studied. Once symptoms have cleared, a subsequent
symptom control may be achieved using an on demand regimen of 10 mg
once daily as needed.
Zollinger – Ellison syndrome
The recommended starting dose for adults is 60 mg once daily. The dose may
be titrated, reaching up to 120 mg / day according to individual patient
needs. A single daily dose of up to 100 mg / day may be administered. It may
be necessary to separate daily doses of 120 mg in two doses of 60 mg. The
treatment should be continued according to clinical indication.
Eradication of Helicobacter Pylori
Patients infected with H. Pylori should be treated with eradication therapy. We
recommend the administration of the following combinations for 7 days.
Rabec® 20 mg twice daily + clarithromycin 500 mg twice daily + amoxicillin
1g twice daily.
In the case of indications requiring a single daily dose, it must be
administered before the meal. While neither the time of day it is ingested nor
the combination with food has been shown to affect the activity of
Rabeprazole, this regimen facilitates adherence to treatment.
Hepatic and renal impairment: No dosage adjustment is necessary in
patients with renal or hepatic impairment. See warnings and precautions for
use of Rabec® in patients with severe liver failure.
Pediatric use: The use of Rabec® in children is not recommended, since there
is no experience with its use in this age group.
Hipersensitivity to the active drug or to any component of the formulation.
Severe hepatic failure. Pregnancy. Lactation.
Because the symptomatic response to treatment with Rabeprazole does not
rule out the presence of gastric or esophageal carcinoma, it is recommended
to exclude the possibility of this diagnosis before starting treatment with Rabec®.
Patients receiving long-term treatment (particularly those treated for more
than a year) should be evaluated regularly by their doctor.
The risk of cross-hypersensitivity with other inhibitors of proton pump or
benzimidazole derivatives can not be excluded.
The tablets should be swallowed whole without chewing or breaking them.
Rabec® is not recommended for use in children since safety and efficacy in
children has not been established.
There have been postmarketing Rabeprazole reports of blood dyscrasias
(thrombocytopenia and neutropenia). In most cases in which an alternative
etiology could not be identified, these events were not complicated and
resolved on discontinuation of the use of Rabeprazole.
Changes in liver enzymes have been observed and have been reported in
clinical studies. In most cases in which an alternative etiology could not be
identified, these events were not complicated and resolved on discontinuation
of the use of Rabeprazole.
No significant disorders were observed during treatment with Rabeprazole in
patients with mild or moderate hepatic dysfunction in controlled studies.
However, since there is no clinical data on the use of Rabeprazole in severe
liver dysfunction, we recommend close medical supervision if used in
patients with this disease.
Concomitant administration of atazanavir with Rabec® is not recommended.
Since Rabeprazole inhibits gastric acid secretion, interaction may occur with
drugs whose absorption depends on gastric pH. For example, coadministration
of Rabeprazole with ketoconazole or itraconazole, or digoxin may reduce
plasma levels of antifungals and increase levels of digoxin. For this reason,
some patients may require dosage adjustment of these drugs.
In clinical studies, no interaction was observed with concomitant use of liquid
antacids and Rabeprazole.
Coadministration of atazanavir 300 mg / ritonavir 10 mg and omeprazole (40
mg once daily) or atazanavir 400 mg with lansoprazole (60 mg / day) to
healthy volunteers resulted in a substantial reduction in atazanavir exposure.
The absorption of atazanavir is pH dependent. Although not studied, it is
expected that similar results are obtained with other proton pump inhibitors.
For this reason, inhibitors of proton pump, including Rabeprazole, should not
be administered in conjunction with atazanavir.
Pregnancy and lactation
Pregnancy: Rabec® is contraindicated during pregnancy. There are no data
on the safety of Rabeprazole in human pregnancy. Studies in rabbits and rats
revealed no evidence of impaired fertility or harm to the fetus secondary to
Lactation: Rabec® is contraindicated during lactation. It is not known if
rabeprazole is excreted in breast milk. There have been no studies in women
during lactation. However rabeprazole is excreted in breast secretions of rats.
Pediatric use: The use of Rabec® in children is not recommended, since there
is no experience with its use in this age group.
Limited information is available regarding accidental or deliberate overdose.
The maximum exposure has not exceeded 60 mg twice daily or 160 mg once
daily. In general the effects are minimal, and represent the known adverse
event profile of the product, reversing without additional medication. There is
no known antidote. Rabeprazole is extensively bound to proteins and therefore
is not dialysed. Treatment should be symptomatic and general supportive
measures should be taken.
In the case of a possible overdose, seek medical attention in the nearest
hospital or refer to the nearest toxicology center.
Do not expose to temperatures exceeding 25 ºC. Do not place in refrigerator
or freezer. Keep the product in its original packaging.