Rabeprazole tablets are indicated for the treatment of:
Active duodenal ulcer
Active benign gastric ulcer
Symptomatic erosive or ulcerative gastro-oesophageal reflux disease (GORD).
Gastro-Oesophageal Reflux Disease Long-term Management (GORD Maintenance)
Symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease (symptomatic
GORD)
Zollinger-Ellison Syndrome.
In combination with appropriate antibacterial therapeutic regimens for the eradication of Helicobacter
pylori in patients with peptic ulcer disease. See section 4.2.

Adults/older people:
Active Duodenal Ulcer and Active Benign Gastric Ulcer: The recommended oral dose for both active
duodenal ulcer and active benign gastric ulcer is 20mg to be taken once daily in the morning.
Most patients with active duodenal ulcer heal within four weeks. However a few patients may require
an additional four weeks of therapy to achieve healing. Most patients with active benign gastric ulcerheal within six weeks. However again a few patients may require an additional six weeks of therapy to
achieve healing.
Erosive or Ulcerative Gastro-Oesophageal Reflux Disease (GORD): The recommended oral dose for
this condition is 20mg to be taken once daily for four to eight weeks.
Gastro-Oesophageal Reflux Disease Long-term Management (GORD Maintenance): For long-term
management, a maintenance dose of Rabeprazole 20 mg or 10 mg once daily can be used depending
upon patient response.
Symptomatic treatment of moderate to very severe gastro-oesophageal reflux disease (symptomatic
GORD): 10mg once daily in patients without oesophagitis. If symptom control has not been achieved
during four weeks, the patient should be further investigated. Once symptoms have resolved,
subsequent symptom control can be achieved using an on-demand regimen taking 10mg once daily
when needed.
Zollinger-Ellison Syndrome: The recommended adult starting dose is 60 mg once a day. The dose may
be titrated upwards to 120 mg/day based on individual patient needs. Single daily doses up to 100
mg/day may be given. 120 mg dose may require divided doses, 60 mg twice daily. Treatment should
continue for as long as clinically indicated.
Eradication of H. pylori: Patients with H. pylori infection should be treated with eradication therapy.
The following combination given for 7 days is recommended.
Rabeprazole 20mg twice daily + clarithromycin 500mg twice daily and amoxicillin 1g twice daily.
For indications requiring once daily treatment Rabeprazole tablets should be taken in the morning,
before eating; and although neither the time of day nor food intake was shown to have any effect on
rabeprazole sodium activity, this regimen will facilitate treatment compliance.
Patients should be cautioned that the Rabeprazole tablets should not be chewed or crushed, but should
be swallowed whole.
Renal and hepatic impairment:
No dosage adjustment is necessary for patients with renal or hepatic impairment.
See section 4.4 Special Warnings and Precautions for Use of Rabeprazole in the treatment of patients
with severe hepatic impairment.
Children:
Rabeprazole is not recommended for use in children, as there is no experience of its use in this group.

Symptomatic response to therapy with Rabeprazole sodium does not preclude the presence of gastric or
oesophageal malignancy, therefore the possibility of malignancy should be excluded prior to
commencing treatment with Rabeprazole
Patients on long-term treatment (particularly those treated for more than a year) should be kept under
regular surveillance.
A risk of cross-hypersensitivity reactions with other proton pump inhibitor or substituted
benzimidazoles cannot be excluded.
Patients should be cautioned that Rabeprazole tablets should not be chewed or crushed, but should be
swallowed whole.
Rabeprazole is not recommended for use in children, as there is no experience of its use in this group.
There have been post marketing reports of blood dyscrasias (thrombocytopenia and neutropenia). In the
majority of cases where an alternative aetiology cannot be identified, the events were uncomplicated
and resolved on discontinuation of rabeprazole.
Hepatic enzyme abnormalities have been seen in clinical trials and have also been reported since market
authorisation. In the majority of cases where an alternative aetiology cannot be identified, the events
were uncomplicated and resolved on discontinuation of rabeprazole.
No evidence of significant drug related safety problems was seen in a study of patients with mild to
moderate hepatic impairment versus normal age and sex matched controls. However because there are
no clinical data on the use of Rabeprazole in the treatment of patients with severe hepatic dysfunction
the prescriber is advised to exercise caution when treatment with Rabeprazole is first initiated in such
patients.
Co-administration of atazanavir with Rabeprazole is not recommended (see section 4.5).
Treatment with proton pump inhibitors, including Rabeprazole, may possibly increase the risk of
gastrointestinal infections such as Salmonella, Campylobacter and Clostridium difficile (see section
5.1).Proton pump inhibitors, especially if used in high doses and over long durations (>1 year), may
modestly increase the risk of hip, wrist and spine fracture, predominantly in older people or in presence
of other recognised risk factors. Observational studies suggest that proton pump inhibitors may increase
the overall risk of fracture by 10–40%. Some of this increase may be due to other risk factors. Patients
at risk of osteoporosis should receive care according to current clinical guidelines and they should have
an adequate intake of vitamin D and calcium.
Severe hypomagnesaemia has been reported in patients treated with proton pump inhibitors like
Rabeprazole for at least three months, and in most cases for a year. Serious manifestations of
hypomagnesaemia such as fatigue, tetany, delirium, convulsions, dizziness and ventricular arrhythmia
can occur but they may begin insidiously and be overlooked. In most affected patients,
hypomagnesaemia improved after magnesium replacement and discontinuation of the proton pump
inhibitor.
For patients expected to be on prolonged treatment or who take proton pump inhibitors with digoxin or
drugs that may cause hypomagnesaemia (e.g., diuretics), health care professionals should consider
measuring magnesium levels before starting proton pump inhibitor treatment and periodically during
treatment.
Concomitant use of Rabeprazole with Methotrexate
Literature suggests that concomitant use of PPIs with methotrexate (primarily at high dose; see
methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its
metabolite, possibly leading to methotrexate toxicities. In high-dose methotrexate administration, a
temporary withdrawal of the PPI may be considered in some patients.
Influence on vitamin B12 absorption
Rabeprazole sodium, as all acid-blocking medicines, may reduce the absorption of vitamin B12
(cyanocobalamin) due to hypo- or a- chlorhydria. This should be considered in patients with reduced
body stores or risk factors for reduced vitamin B12 absorption on long-term therapy or if respective
clinical symptoms are observed.
Subacute cutaneous lupus erythematosus (SCLE)
Proton pump inhibitors are associated with very infrequent cases of SCLE. If lesions occur, especially
in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical help
promptly and the health care professional should consider stopping Rabeprazole SCLE after previous inhibitors.
Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine tumours.
To avoid this interference, Rabeprazole treatment should be stopped for at least 5 days before CgA
measurements (see section 5.1). If CgA and gastrin levels have not returned to reference range after
initial measurement, measurements should be repeated 14 days after cessation of proton pump inhibitor
treatment.

Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An
interaction with compounds whose absorption is pH dependent may occur. Co-administration of
rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal
plasma levels. Therefore individual patients may need to be monitored to determine if a dosage
adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with Rabeprazole
In clinical trials, antacids were used concomitantly with the administration of Rabeprazole and, in a
specific drug-drug interaction study, no interaction with liquid antacids was observed.
Co-administration of atazanavir 300 mg/ritonavir 100 mg with omeprazole (40 mg once daily) or
atazanavir 400 mg with lansoprazole (60 mg once daily) to healthy volunteers resulted in a substantial
reduction in atazanavir exposure. The absorption of atazanavir is pH dependent. Although not studied,
similar results are expected with other proton pump inhibitors. Therefore PPIs, including rabeprazole,
should not be co-administered with atazanavir (see Section 4.4).
Methotrexate
Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that
concomitant administration of PPIs and methotrexate (primarily at high dose; see methotrexate
prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite
hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPIs have
been conducted.

Pregnancy:
There are no data on the safety of rabeprazole in human pregnancy.
Reproduction studies performed in rats and rabbits have revealed no evidence of impaired fertility or
harm to the foetus due to rabeprazole sodium, although low foeto-placental transfer occurs in rats.
Rabeprazole is contraindicated during pregnancy.
Breast-feeding:
It is not known whether rabeprazole sodium is excreted in human breast milk. No studies in breastfeeding
women have been performed. Rabeprazole sodium is however excreted in rat mammary
secretions. Therefore Rabeprazole should not be used during breast-feeding.

Based on the pharmacodynamic properties and the adverse events profile, it is unlikely that
Rabeprazole would cause an impairment of driving performance or compromise the ability to use
machinery. If however, alertness is impaired due to somnolence, it is recommended that driving and
operating complex machinery be avoided.

The most commonly reported adverse drug reactions, during controlled clinical trials with rabeprazole
were headache, diarrhoea, abdominal pain, asthenia, flatulence, rash and dry mouth. The majority of
adverse events experienced during clinical studies were mild or moderate in severity, and transient in
nature.
The following adverse events have been reported from clinical trial and post-marketing experience.
Frequencies are defined as: common (> 1/100, < 1/10), uncommon (> 1/1,000, < 1/100), rare
(>1/10,000, <1/1000) very rare (<1/10,000), Not Known (cannot be estimated from the available data).
System Organ
Class Common Uncommon Rare Very Rare Not Known
Infections and
infestations Infection
Blood and the
lymphatic system
disorders
Neutropenia
Leucopenia
Thrombocytopenia

Leucocytosis
Immune system
disorders Hypersensitivity1,2
Metabolism and
nutrition
disorders Anorexia
Hyponatremia
Hypomagnesaemia4
Psychiatric
disorders Insomnia Nervousness Depression Confusion
Nervous system
disorders
Headache
Dizziness Somnolence
Eye disorders Visual disturbance
Vascular
Disorders Peripheral Oedema
Respiratory,
thoracic and
mediastinal
disorders
Cough
Pharyngitis
Rhinitis
Bronchitis
Sinusitis
Gastrointestinal
disorders
Diarrhoea
Vomiting
Nausea
Abdominal
pain
Constipation
Flatulence
Fundic Gland
Polyps
(Benign)
Dyspepsia
Dry mouth
Eructation
Gastritis
Stomatitis
Taste disturbance
Hepato-biliary
disorders
Hepatitis
Jaundice
Hepatic
encephalopathy3
Skin and
subcutaneous
tissue disorders
Rash
Erythema2
Pruritus
Sweating
Bullous reactions2
Erythema
multiforme,
toxic
epidermal
necrolysis
(TEN),
Stevens-
Johnson
syndrome
(SJS)
Subacute cutaneous
lupus
erythematosus4
Musculoskeletal Non-specific Myalgia connective tissue
and bone
disorders
pain
Back pain
Leg cramps
Arthralgia
Fracture of the
hip, wrist or
spine 4
Renal and
urinary disorders
Urinary tract
infection
Interstitial
nephritis
Reproductive
system and
breast disorders Gynaecomastia
General
disorders and
administration
site conditions
Asthenia
Influenza like
illness
Chest pain
Chills
Pyrexia
Investigations
Increased hepatic
enzymes3 Weight increased
1 Includes facial swelling, hypotension and dyspnoea
2 Erythema, bullous reactions and hypersensitivity reactions have usually resolved after discontinuation
of therapy.
3 Rare reports of hepatic encephalopathy have been received in patients with underlying cirrhosis. In
treatment of patients with severe hepatic dysfunction the prescriber is advised to exercise caution when
treatment with Rabeprazole is first initiated in such patients (see section 4.4).
4 See Special warnings and precautions for use (4.4)
To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
 Fax: +966-11-205-7662
 Call NPC at +966-11-2038222,
Exts: 2317-2356-2353-2354-2334-2340.
 Toll free phone: 8002490000
 E-mail: npc.drug@sfda.gov.sa
 Website: www.sfda.gov.sa/npc

Experience to date with deliberate or accidental overdose is limited. The maximum established
exposure has not exceeded 60mg twice daily, or 160mg once daily. Effects are generally minimal, representative of the known adverse event profile and reversible without further medical intervention.
No specific antidote is known. Rabeprazole sodium is extensively protein bound and is, therefore, not
dialysable. As in any case of overdose, treatment should be symptomatic and general supportive
measures should be utilised.

Pharmacotherapeutic group: Alimentary tract and metabolism, Drugs for peptic ulcer and gastrooesophageal
reflux disease (GORD), proton pump inhibitors, ATC code: A02B C04
Mechanism of Action: Rabeprazole sodium belongs to the class of anti-secretory compounds, the
substituted benzimidazoles, that do not exhibit anticholinergic or H2 histamine antagonist properties,
but suppress gastric acid secretion by the specific inhibition of the H+/K+-ATPase enzyme (the acid or
proton pump) The effect is dose-related and leads to inhibition of both basal and stimulated acid
secretion irrespective of the stimulus. Animal studies indicate that after administration, rabeprazole
sodium rapidly disappears from both the plasma and gastric mucosa. As a weak base, rabeprazole is
rapidly absorbed following all doses and is concentrated in the acid environment of the parietal cells.
Rabeprazole is converted to the active sulphenamide form through protonation and it subsequently
reacts with the available cysteines on the proton pump.
Anti-secretory Activity: After oral administration of a 20mg dose of rabeprazole sodium the onset of
the anti-secretory effect occurs within one hour, with the maximum effect occurring within two to four
hours. Inhibition of basal and food stimulated acid secretion 23 hours after the first dose of rabeprazole
sodium are 69% and 82% respectively and the duration of inhibition lasts up to 48 hours. The inhibitory
effect of rabeprazole sodium on acid secretion increases slightly with repeated once-daily dosing,
achieving steady state inhibition after three days. When the drug is discontinued, secretory activity
normalises over 2 to 3 days.
Decreased gastric acidity due to any means, including proton pump inhibitors such as rabeprazole,
increases counts of bacteria normally present in the gastrointestinal tract. Treatment with proton pump inhibitors may possibly increase the risk of gastrointestinal infections such
as Salmonella, Campylobacter and Clostridium difficile.
Serum Gastrin Effects: In clinical studies patients were treated once daily with 10 or 20mg rabeprazole
sodium, for up to 43 months duration. Serum gastrin levels increased during the first 2 to 8 weeks
reflecting the inhibitory effects on acid secretion and remained stable while treatment was continued.
Gastrin values returned to pre-treatment levels, usually within 1 to 2 weeks after discontinuation of
therapy.
Human gastric biopsy specimens from the antrum and the fundus from over 500 patients receiving
rabeprazole or comparator treatment for up to 8 weeks have not detected changes in ECL cell histology,
degree of gastritis, incidence of atrophic gastritis, intestinal metaplasia or distribution of H. pylori
infection. In over 250 patients followed for 36 months of continuous therapy, no significant change in
findings present at baseline was observed.
Other Effects: Systemic effects of rabeprazole sodium in the CNS, cardiovascular and respiratory
systems have not been found to date. Rabeprazole sodium, given in oral doses of 20mg for 2 weeks, had
no effect on thyroid function, carbohydrate metabolism, or circulating levels of parathyroid hormone,
cortisol, oestrogen, testosterone, prolactin, cholecystokinin, secretin, glucagon, follicle stimulating
hormone (FSH), luteinising hormone (LH), renin, aldosterone or somatotrophic hormone.
Studies in healthy subjects have shown that rabeprazole sodium does not have clinically significant
interactions with amoxicillin. Rabeprazole does not adversely influence plasma concentrations of
amoxicillin or clarithromycin when co-administered for the purpose of eradicating upper
gastrointestinal H. pylori infection.
During treatment with antisecretory medicinal products, serum gastrin increases in response to the
decreased acid secretion. Also CgA increases due to decreased gastric acidity. The increased CgA level
may interfere with investigations for neuroendocrine tumours.
Available published evidence suggests that proton pump inhibitors should be discontinued between 5
days and 2 weeks prior to CgA measurements. This is to allow CgA levels that might be spuriously
elevated following PPI treatment to return to reference range.

Absorption: Rabeprazole is an enteric-coated (gastro-resistant) tablet formulation of rabeprazole
sodium. This presentation is necessary because rabeprazole is acid-labile.
Absorption of rabeprazole therefore begins only after the tablet leaves the stomach. Absorption is rapid,
with peak plasma levels of rabeprazole occurring approximately 3.5 hours after a 20mg dose. Peak
plasma concentrations (Cmax) of rabeprazole and AUC are linear over the dose range of 10mg to
40mg. Absolute bioavailability of an oral 20mg dose (compared to intravenous administration) is about
52% due in large part to pre-systemic metabolism. Additionally the bioavailability does not appear to
increase with repeat administration. In healthy subjects the plasma half-life is approximately one hour
(range 0.7 to 1.5 hours), and the total body clearance is estimated to be 283 ± 98 ml/min. There was no
clinically relevant interaction with food. Neither food nor the time of day of administration of the
treatment affect the absorption of rabeprazole sodium.
Distribution: Rabeprazole is approximately 97% bound to human plasma proteins.
Metabolism and excretion: Rabeprazole sodium, as is the case with other members of the proton pump
inhibitor (PPI) class of compounds, is metabolised through the cytochrome P450 (CYP450) hepatic
drug metabolising system. In vitro studies with human liver microsomes indicated that rabeprazole
sodium is metabolised by isoenzymes of CYP450 (CYP2C19 and CYP3A4). In these studies, at
expected human plasma concentrations rabeprazole neither induces nor inhibits CYP3A4; and although
in vitro studies may not always be predictive of in vivo status these findings indicate that no interaction
is expected between rabeprazole and cyclosporin. In humans the thioether (M1) and carboxylic acid
(M6) are the main plasma metabolites with the sulphone (M2), desmethyl-thioether (M4) and
mercapturic acid conjugate (M5) minor metabolites observed at lower levels. Only the desmethyl
metabolite (M3) has a small amount of anti-secretory activity, but it is not present in plasma.
Following a single 20mg 14C 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
metabolites: a mercapturic acid conjugate (M5) and a carboxylic 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 20 mg dose of rabeprazole.
Renal dysfunction: In patients with stable, end-stage, renal failure requiring maintenance haemodialysis
(creatinine clearance ≤5ml/min/1.73 m2), 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 20 mg 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 20 mg 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.
Older people: Elimination of rabeprazole was somewhat decreased in older people. Following 7 days of
daily dosing with 20mg of rabeprazole sodium, the AUC approximately doubled, the Cmax increased
by 60% and t½ 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 t½ which were approximately 1.9 and 1.6 times the corresponding
parameters in extensive metabolisers whilst Cmax had increased by only 40%.

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.

Ludipress, Crospovidone, Magnesium oxide, Microcrystalline Cellulose (Avicel),
Povidone K-30, Hydroxypropylcellulose, Colloidal Silicon Dioxide (Aerosil 200),
Magnesium Stearate, Opadry White, Hydroxypropylcellulose AS (Aqoat HF), Sodium Hydroxide,
Ammonia 30 % , Acryl-eze, Purified Water

Not applicable.

Do not store above 25°C. Protect from Light.

Alu - Alu blister

No special requirements.