Aciloc 40 capsules are indicated for:
Adults
• Treatment of duodenal ulcers
• Prevention of relapse of duodenal ulcers
• Treatment of gastric ulcers
• Prevention of relapse of gastric ulcers
• In combination with appropriate antibiotics, Helicobacter pylori (H. pylori) eradication in peptic
ulcer disease
• Treatment of NSAID-associated gastric and duodenal ulcers
• Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk
• Treatment of reflux oesophagitis
• Long-term management of patients with healed reflux oesophagitis

• Treatment of symptomatic gastro-oesophageal reflux disease
• Treatment of Zollinger-Ellison syndrome
Paediatric use
Children over 1 year of age and 10 kg
• Treatment of reflux oesophagitis
• Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux disease
Children and adolescents over 4 years of age
• In combination with antibiotics in treatment of duodenal ulcer caused by H. pylori

Posology in adults
Treatment of duodenal ulcers
The recommended dose in patients with an active duodenal ulcer is Aciloc 20 mg once daily. In
most patients healing occurs within two weeks. For those patients who may not be fully healed
after the initial course, healing usually occurs during a further two weeks treatment period. In
patients with poorly responsive duodenal ulcer Aciloc 40 mg once daily is recommended and
healing is usually achieved within four weeks.
Prevention of relapse of duodenal ulcers
For the prevention of relapse of duodenal ulcer in H. pylori negative patients or when H.
pylori eradication is not possible the recommended dose is Aciloc 20 mg once daily. In some
patients a daily dose of 10 mg may be sufficient. In case of therapy failure, the dose can be
increased to 40 mg.
Treatment of gastric ulcers
The recommended dose is Aciloc 20 mg once daily. In most patients healing occurs within four
weeks. For those patients who may not be fully healed after the initial course, healing usually
occurs during a further four weeks treatment period. In patients with poorly responsive gastric
ulcer Aciloc 40 mg once daily is recommended and healing is usually achieved within eight
weeks.

Prevention of relapse of gastric ulcers
For the prevention of relapse in patients with poorly responsive gastric ulcer the recommended
dose is Aciloc 20 mg once daily. If needed the dose can be increased to Aciloc 40 mg once daily.
H. pylori eradication in peptic ulcer disease
For the eradication of H. pylori the selection of antibiotics should consider the individual patient's
drug tolerance, and should be undertaken in accordance with national, regional and local
resistance patterns and treatment guidelines.
• Aciloc 20 mg + clarithromycin 500 mg + amoxicillin 1,000 mg, each twice daily for one week, or
• Aciloc 20 mg + clarithromycin 250 mg (alternatively 500 mg) + metronidazole 400 mg (or 500
mg or tinidazole 500 mg), each twice daily for one week or
• Aciloc 40 mg once daily with amoxicillin 500 mg and metronidazole 400 mg (or 500 mg or
tinidazole 500 mg), both three times a day for one week.
In each regimen, if the patient is still H. pylori positive, therapy may be repeated.
Treatment of NSAID-associated gastric and duodenal ulcers
For the treatment of NSAID-associated gastric and duodenal ulcers, the recommended dose is
Aciloc 20 mg once daily. In most patients healing occurs within four weeks. For those patients
who may not be fully healed after the initial course, healing usually occurs during a further four
weeks treatment period.
Prevention of NSAID-associated gastric and duodenal ulcers in patients at risk
For the prevention of NSAID-associated gastric ulcers or duodenal ulcers in patients at risk (age>
60, previous history of gastric and duodenal ulcers, previous history of upper GI bleeding) the
recommended dose is Aciloc 20 mg once daily.
Treatment of reflux oesophagitis
The recommended dose is Aciloc 20 mg once daily. In most patients healing occurs within four
weeks. For those patients who may not be fully healed after the initial course, healing usually
occurs during a further four weeks treatment period.
In patients with severe oesophagitis Aciloc 40 mg once daily is recommended and healing isusually achieved within eight weeks.
Long-term management of patients with healed reflux oesophagitis
For the long-term management of patients with healed reflux oesophagitis the recommended
dose is Aciloc 10 mg once daily. If needed, the dose can be increased to Aciloc 20-40 mg once
daily.
Treatment of symptomatic gastro-oesophageal reflux disease
The recommended dose is Aciloc 20 mg daily. Patients may respond adequately to 10 mg daily,
and therefore individual dose adjustment should be considered.
If symptom control has not been achieved after four weeks treatment with Aciloc 20 mg daily,
further investigation is recommended.
Treatment of Zollinger-Ellison syndrome
In patients with Zollinger-Ellison syndrome the dose should be individually adjusted and treatment
continued as long as clinically indicated. The recommended initial dose is Aciloc 60 mg daily. All
patients with severe disease and inadequate response to other therapies have been effectively
controlled and more than 90% of the patients maintained on doses of Aciloc 20-120 mg daily.
When dose exceed Aciloc 80 mg daily, the dose should be divided and given twice daily.
Posology in children
Children over 1 year of age and 10 kg
Treatment of reflux oesophagitis
Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux disease
The posology recommendations are as follows:

- 1 year of age  (Weight 10-20 kg) 10 mg once daily. The dose can be increased to 20 mg once daily if needed
- 2 years of age (Weight > 20 kg ) 20 mg once daily. The dose can be increased to 40 mg once daily if needed

Reflux oesophagitis: The treatment time is 4-8 weeks.
Symptomatic treatment of heartburn and acid regurgitation in gastro-oesophageal reflux
disease: The treatment time is 2–4 weeks. If symptom control has not been achieved after 2–4
weeks the patient should be investigated further.
Children and adolescents over 4 years of age
Treatment of duodenal ulcer caused by H. pylori
When selecting appropriate combination therapy, consideration should be given to official
national, regional and local guidance regarding bacterial resistance, duration of treatment (most
commonly 7 days but sometimes up to 14 days), and appropriate use of antibacterial agents.
The treatment should be supervised by a specialist.
The posology recommendations are as follows:

(Weight 15–30 kg): Combination with two antibiotics: Aciloc 10 mg, amoxicillin 25 mg/kg body
weight and clarithromycin 7.5 mg/kg body weight are all administrated together two times daily for one week.
(Weight 31–40 kg): Combination with two antibiotics: Aciloc 20 mg, amoxicillin 750 mg and
clarithromycin 7.5 mg/kg body weight are all administrated two times daily for one week.
(Weight > 40 kg): Combination with two antibiotics: Aciloc 20 mg, amoxicillin 1 g and
clarithromycin 500 mg are all administrated two times daily for one week.

Special populations
Impaired renal function
Dose adjustment is not needed in patients with impaired renal function (see section 5.2).
Impaired hepatic function
In patients with impaired hepatic function a daily dose of 10–20 mg may be sufficient

(see section 5.2).
Elderly (> 65 years old)
Dose adjustment is not needed in the elderly (see section 5.2).
Method of administration
It is recommended to take Aciloc capsules in the morning, preferably without food, swallowed
whole with half a glass of water. The capsules must not be chewed or crushed.
For patients with swallowing difficulties and for children who can drink or swallow semi-solid food
Patients can open the capsule and swallow the contents with half a glass of water or after mixing
the contents in a slightly acidic fluid e.g., fruit juice or applesauce, or in non-carbonated water.
Patients should be advised that the dispersion should be taken immediately (or within 30 minutes)
and always be stirred just before drinking and rinsed down with half a glass of water.
Alternatively patients can suck the capsule and swallow the pellets with half a glass of water. The
enteric-coated pellets must not be chewed..

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment may alleviate symptoms and delay diagnosis. Co-administration of atazanavir with proton pump inhibitors is not recommended (see section 4.5).
If the combination of atazanavir with a proton pump inhibitor is judged unavoidable, close clinical monitoring (e.g virus load) is recommended in combination with an increase in the dose of
atazanavir to 400 mg with 100 mg of ritonavir; omeprazole 20 mg should not be exceeded.
Omeprazole, as all acid-blocking medicinal products, may reduce the absorption of vitamin B12
(cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with reduced
body stores or risk factors for reduced vitamin B12 absorption on long-term therapy.
Omeprazole is a CYP2C19 inhibitor. When starting or ending treatment with omeprazole, the
potential for interactions with medicinal products metabolised through CYP2C19 should be
considered. An interaction is observed between clopidogrel and omeprazole (see section 4.5). The
clinical relevance of this interaction is uncertain. As a precaution, concomitant use of omeprazole
and clopidogrel should be discouraged.
Severe hypomagnesaemia has been reported in patients treated with PPIs like omeprazole 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 PPI.
For patients expected to be on prolonged treatment or who take PPIs with digoxin or medicinal
products that may cause hypomagnesaemia (e.g., diuretics), health care professionals should
consider measuring magnesium levels before starting PPI treatment and periodically during
treatment.
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 the elderly 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.
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 Omeprazole.
SCLE after previous treatment with a proton pump inhibitor may increase the risk of SCLE with
other proton pump inhibitors.
Interference with laboratory tests
Increased Chromogranin A (CgA) level may interfere with investigations for neuroendocrine
tumours. To avoid this interference, [nationally completed name] 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.
Paediatric population
Some children with chronic illnesses may require long-term treatment although it is not
recommended.
Treatment with proton pump inhibitors may lead to slightly increased risk of gastrointestinal
infections such as Salmonella and Campylobacter and, in hospitalised patients, possibly
also Clostridium difficile (see section 5.1).
As in all long-term treatments, especially when exceeding a treatment period of 1 year, patients
should be kept under regular surveillance.
Omeprazole contains sucrose and sodium
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or
sucrose-isomaltase insufficiency should not take this medicinal product.
This medicinal product contains less than 1 mmol (23 mg) sodium per gastro-resistant hard
capsule, that is to say essentially 'sodium-free'.

Effects of Omeprazole on the pharmacokinetics of other active substances
Active substances with pH dependent absorption
The decreased intragastric acidity during treatment with Omeprazole might increase or decrease
the absorption of active substances with a gastric pH dependent absorption.
Nelfinavir, atazanavir
The plasma levels of nelfinavir and atazanavir are decreased in case of co-administration with
Omeprazole.
Concomitant administration of Omeprazole with nelfinavir is contraindicated (see section 4.3). Coadministration
of Omeprazole (40 mg once daily) reduced mean nelvinavir exposure by ca. 40%
and the mean exposure of the pharmacologically active metabolite M8 was reduced by ca. 75 –
90%. The interaction may also involve CYP2C19 inhibition.
Concomitant administration of Omeprazole with atazanavir is not recommended (see section 4.4).
Concomitant administration of Omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir
100 mg to healthy volunteers resulted in a 75% decrease of the atazanavir exposure. Increasing
the atazanavir dose to 400 mg did not compensate for the impact of Omeprazole on atazanavir
exposure. The co-administration of Omeprazole (20 mg once daily) with atazanavir 400
mg/ritonavir 100 mg to healthy volunteers resulted in a decrease of approximately 30% in the
atazanavir exposure as compared to atazanavir 300 mg/ritonavir 100 mg once daily.
Digoxin
Concomitant treatment with Omeprazole (20 mg daily) and digoxin in healthy subjects increased
the bioavailability of digoxin by 10%. Digoxin toxicity has been rarely reported. However caution
should be exercised when Omeprazole is given at high doses in elderly patients. Therapeutic
drug monitoring of digoxin should be then be reinforced.
Clopidogrel
In a crossover clinical study, clopidogrel (300 mg loading dose followed by 75 mg/day) alone and
with Omeprazole (80 mg at the same time as clopidogrel) were administered for 5 days. The
exposure to the active metabolite of clopidogrel was decreased by 46% (Day 1) and 42% (Day 5)
when clopidogrel and Omeprazole were administered together. Mean inhibition of platelet

aggregation (IPA) was diminished by 47% (24 hours) and 30% (Day 5) when clopidogrel and
Omeprazole were administered together. In another study it was shown that administering
clopidogrel and Omeprazole at different times did not prevent their interaction that is likely to be
driven by the inhibitory effect of Omeprazole on CYP2C19. Inconsistent data on the clinical
implications of this PK/PD interaction in terms of major cardiovascular events have been reported
from observational and clinical studies.
Other active substances
The absorption of posaconazole, erlotinib, ketoconazol and itraconazol is significantly reduced
and thus clinical efficacy may be impaired. For posaconazol and erlotinib concomitant use should
be avoided.
Active substances metabolised by CYP2C19
Omeprazole is a moderate inhibitor of CYP2C19, the major Omeprazole metabolising enzyme.
Thus, the metabolism of concomitant active substances also metabolised by CYP2C19, may be
decreased and the systemic exposure to these substances increased. Examples of such drugs
are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.
Cilostazol
Omeprazole, given in doses of 40 mg to healthy subjects in a cross-over study, increased
Cmax and AUC for cilostazol by 18% and 26% respectively, and one of its active metabolites by
29% and 69% respectively.
Phenytoin
Monitoring phenytoin plasma concentration is recommended during the first two weeks after
initiating Omeprazole treatment and, if a phenytoin dose adjustment is made, monitoring and a
further dose adjustment should occur upon ending Omeprazole treatment.
Unknown mechanism
Saquinavir
Concomitant administration of Omeprazole with saquinavir/ritonavir resulted in increased plasma
levels up to approximately 70% for saquinavir associated with good tolerability in HIV-infected
patients.

Tacrolimus
Concomitant administration of Omeprazole has been reported to increase the serum levels of
tacrolimus. A reinforced monitoring of tacrolimus concentrations as well as renal function
(creatinine clearance) should be performed, and dosage of tacrolimus adjusted if needed.
Effects of other active substances on the pharmacokinetics of Omeprazole
Inhibitors CYP2C19 and/or CYP3A4
Since Omeprazole is metabolised by CYP2C19 and CYP3A4, active substances known to inhibit
CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may lead to increased
Omeprazole serum levels by decreasing Omeprazole's rate of metabolism. Concomitant
voriconazole treatment resulted in more than doubling of the Omeprazole exposure. As high
doses of Omeprazole have been well-tolerated adjustment of the Omeprazole dose is not
generally required. However, dose adjustment should be considered in patients with severe
hepatic impairment and if long-term treatment is indicated.
Inducers of CYP2C19 and/or CYP3A4
Active substances known to induce CYP2C19 or CYP3A4 or both (such as rifampicin and St
John's wort) may lead to decreased Omeprazole serum levels by increasing Omeprazole's rate of
metabolism.

Pregnancy
Results from three prospective epidemiological studies (more than 1000 exposed outcomes)
indicate no adverse events of omeprazole on pregnancy or on the health of the foetus/newborn
child. Omeprazole can be used during pregnancy.
Breast-feeding
Omeprazole is excreted in breast milk but is not likely to influence the child when therapeutic
doses are used.

Fertility
Animal studies with the racemic mixture omeprazole, given by oral administration do not indicate
effects with respect to fertility.

Omeprazole is not likely to affect the ability to drive or use machines. Adverse reactions such as
dizziness and visual disturbances may occur (see section 4.8). If affected, patients should not drive
or operate machinery.

The most common side effects (1-10% of patients) are headache, abdominal pain, constipation,
diarrhoea, flatulence and nausea/vomiting.
The following adverse drug reactions have been identified or suspected in the clinical trials
programme for Omeprazole and post-marketing. None was found to be dose-related. Adverse
reactions listed below are classified according to frequency and System Organ Class (SOC).
Frequency categories are defined according to the following convention: Very common ( 1/10),
Common ( 1/100 to < 1/10), Uncommon ( 1/1,000 to < 1/100), Rare ( 1/10,000 to < 1/1,000),
Very rare (< 1/10,000), Not known (cannot be estimated from the available data).

SOC/frequency      Adverse reaction Blood and lymphatic system disorders

Rare:                        Leukopenia, thrombocytopenia

Very rare:                 Agranulocytosis, pancytopenia

Immune system disorders

Rare:

Hypersensitivity reactions e.g. fever, angioedema and anaphylactic

reaction/shock

Metabolism and nutrition disorders

Rare:                        Hyponatraemia

Very rare:                 Hypomagnesaemia

Psychiatric disorders

Uncommon:             Insomnia

Rare:                        Agitation, confusion, depression

Very rare:                 Aggression, hallucinations

Nervous system disorders

Common:                 Headache

Uncommon:             Dizziness, paraesthesia, somnolence Rare:                        Taste 
disturbance

Eye disorders

Rare:                        Blurred vision Ear and labyrinth disorders Uncommon:             
Vertigo

Respiratory, thoracic and mediastinal disorders

Rare:                        Bronchospasm

Gastrointestinal disorders

Common:                 Abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting Rare:  
                      Dry mouth, stomatitis, gastrointestinal candidiasis

Hepatobiliary disorders

Uncommon:             Increased liver enzymes

Rare:                        Hepatitis with or without jaundice

Very rare:                 Hepatic failure, encephalopathy in patients with pre-existing liver 
disease

Skin and subcutaneous tissue disorders

Uncommon:             Dermatitis, pruritus, rash, urticaria Rare:                        Alopecia, 
photosensitivity

Very rare:                 Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal 
necrolysis (TEN)

Musculoskeletal and connective tissue disorders

Rare:                        Arthralgia, myalgia

Very rare:                 Muscular weakness

Renal and urinary disorders

Rare:                        Interstitial nephritis

Reproductive system and breast disorders

Very rare:                 Gynaecomastia

General disorders and administration site conditions

Uncommon:             Malaise, peripheral oedema Rare:                        Increased sweating

Paediatric population
The safety of Omeprazole has been assessed in a total of 310 children aged 0 to 16 years with
acid-related disease. There are limited long term safety data from 46 children who received
maintenance therapy of Omeprazole during a clinical study for severe erosive oesophagitis for up
to 749 days. The adverse event profile was generally the same as for adults in short- as well as in
long-term treatment. There are no long term data regarding the effects of Omeprazole treatment
on puberty and growth.

To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
o Fax: +966-11-205-7662
o Call NPC at +966-11-2038222, Ext: 2317-2356-2340.
o Reporting hotline: 19999
o E-mail: npc.drug@sfda.gov.sa
o Website: www.sfda.gov.sa/npc
• Other GCC States:
− Please contact the relevant competent authority.

There is limited information available on the effects of overdoses of Omeprazole in humans. In
the literature, doses of up to 560 mg have been described, and occasional reports have been
received when single oral doses have reached up to 2,400 mg Omeprazole (120 times the usual
recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and
headache have been reported. Also apathy, depression and confusion have been described in
single cases.
The symptoms described have been transient, and no serious outcome has been reported. The
rate of elimination was unchanged (first order kinetics) with increased doses. Treatment, if
needed, is symptomatic.

Pharmacotherapeutic group: Drugs for acid related disorders, drugs for peptic ulcer and gastrooesophageal
reflux disease (GORD), proton pump inhibitors, ATC code: A02BC01
Mechanism of action
Omeprazole, a racemic mixture of two enantiomers reduces gastric acid secretion through a
highly targeted mechanism of action. It is a specific inhibitor of the acid pump in the parietal cell. Itis rapidly acting and provides control through reversible inhibition of gastric acid secretion with
once daily dosing.
Omeprazole is a weak base and is concentrated and converted to the active form in the highly
acidic environment of the intracellular canaliculi within the parietal cell, where it inhibits the
enzyme H+ K+-ATPase - the acid pump. This effect on the final step of the gastric acid formation
process is dose-dependent and provides for highly effective inhibition of both basal acid secretion
and stimulated acid secretion, irrespective of stimulus.
Pharmacodynamic effects
All pharmacodynamic effects observed can be explained by the effect of Omeprazole on acid
secretion.
Effect on gastric acid secretion
Oral dosing with Omeprazole once daily provides for rapid and effective inhibition of daytime and
night-time gastric acid secretion with maximum effect being achieved within 4 days of treatment.
With Omeprazole 20 mg, a mean decrease of at least 80% in 24-hour intragastric acidity is then
maintained in duodenal ulcer patients, with the mean decrease in peak acid output after
pentagastrin stimulation being about 70% 24 hours after dosing.
Oral dosing with Omeprazole 20 mg maintains an intragastric pH of 3 for a mean time of 17
hours of the 24-hour period in duodenal ulcer patients.
As a consequence of reduced acid secretion and intragastric acidity, Omeprazole dosedependently
reduces/normalizes acid exposure of the oesophagus in patients with gastrooesophageal
reflux disease.
The inhibition of acid secretion is related to the area under the plasma concentration-time curve
(AUC) of Omeprazole and not to the actual plasma concentration at a given time.
No tachyphylaxis has been observed during treatment with Omeprazole.
Effect on H. pylori
H. pylori is associated with peptic ulcer disease, including duodenal and gastric ulcer disease. H.
pylori is a major factor in the development of gastritis. H. pylori together with gastric acid are
major factors in the development of peptic ulcer disease. H. pylori is a major factor in the
development of atrophic gastritis which is associated with an increased risk of developing gastric
cancer.
Eradication of H. pylori with Omeprazole and antimicrobials is associated with, high rates of healing and long-term remission of peptic ulcers.
Dual therapies have been tested and found to be less effective than triple therapies. They could,
however, be considered in cases where known hypersensitivity precludes use of any triple
combination.
Other effects related to acid inhibition
During long-term treatment gastric glandular cysts have been reported in a somewhat increased
frequency. These changes are a physiological consequence of pronounced inhibition of acid
secretion, are benign and appear to be reversible.
Decreased gastric acidity due to any means including proton pump inhibitors, increases gastric
counts of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing
drugs may lead to slightly increased risk of gastrointestinal infections such
as Salmonella and Campylobacter.
Chromogranin A (CgA) also increases due to decreased gastric acidity. This CgA modifying effect
can not be demonstrated five days after stopping treatment with PPIs.
Paediatric use
In a non-controlled study in children (1 to 16 years of age) with severe reflux oesophagitis,
Omeprazole at doses of 0.7 to 1.4 mg/kg improved oesophagitis level in 90% of the cases and
significantly reduced reflux symptoms. In a single-blind study, children aged 0–24 months with
clinically diagnosed gastro-oesophageal reflux disease were treated with 0.5, 1.0 or 1.5 mg
Omeprazole/kg. The frequency of vomiting/regurgitation episodes decreased by 50% after 8
weeks of treatment irrespective of the dose.
Eradication of H. pylori in children
A randomised, double blind clinical study (Héliot study) concluded that Omeprazole in
combination with two antibiotics (amoxicillin and clarithromycin), was safe and effective in the
treatment of H. pylori infection in children age 4 years old and above with gastritis: H.
pylori eradication rate: 74.2% (23/31 patients) with Omeprazole + amoxicillin + clarithromycin
versus 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, there was no evidence of
any clinical benefit with respect to dyspeptic symptoms. This study does not support any
information for children aged less than 4 years.

Absorption
Omeprazole and Omeprazole magnesium are acid labile and are therefore administered orally as
enteric-coated granules in capsules or tablets. Absorption of Omeprazole is rapid, with peak
plasma levels occurring approximately 1-2 hours after dose. Absorption of Omeprazole takes
place in the small intestine and is usually completed within 3-6 hours. Concomitant intake of food
has no influence on the bioavailability. The systemic availability (bioavailability) from a single oral
dose of Omeprazole is approximately 40%. After repeated once-daily administration, the
bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight.
Omeprazole is 97% plasma protein bound.
Metabolism
Omeprazole is completely metabolised by the cytochrome P450 system (CYP). The major part of
its metabolism is dependent on the polymorphically expressed CYP2C19, responsible for the
formation of hydroxyl Omeprazole, the major metabolite in plasma. The remaining part is
dependent on another specific isoform, CYP3A4, responsible for the formation of Omeprazole
sulphone. As a consequence of high affinity of Omeprazole to CYP2C19, there is a potential for
competitive inhibition and metabolic drug-drug interactions with other substrates for CYP2C19.
However, due to low affinity to CYP3A4, Omeprazole has no potential to inhibit the metabolism of
other CYP3A4 substrates. In addition, Omeprazole lacks an inhibitory effect on the main CYP
enzymes.
Approximately 3% of the Caucasian population and 15-20% of Asian populations lack a functional
CYP2C19 enzyme and are called poor metabolisers. In such individuals the metabolism of
Omeprazole is probably mainly catalysed by CYP3A4. After repeated once-daily administration of
20 mg Omeprazole, the mean AUC was 5 to 10 times higher in poor metabolisers than in
subjects having a functional CYP2C19 enzyme (extensive metabolisers). Mean peak plasma
concentrations were also higher, by 3 to 5 times. These findings have no implications for the
posology of Omeprazole.
Excretion
The plasma elimination half-life of Omeprazole is usually shorter than one hour both after single
and repeated oral once-daily dosing. Omeprazole is completely eliminated from plasma between
doses with no tendency for accumulation during once-daily administration. Almost 80% of an oral
dose of Omeprazole is excreted as metabolites in the urine, the remainder in the faeces, primarily originating from bile secretion.
The AUC of Omeprazole increases with repeated administration. This increase is dosedependent
and results in a non-linear dose-AUC relationship after repeated administration. This
time- and dose-dependency is due to a decrease of first pass metabolism and systemic clearance
probably caused by an inhibition of the CYP2C19 enzyme by Omeprazole and/or its metabolites
(e.g. the sulphone).
No metabolite has been found to have any effect on gastric acid secretion.
Special populations
Impaired hepatic function
The metabolism of Omeprazole in patients with liver dysfunction is impaired, resulting in an
increased AUC. Omeprazole has not shown any tendency to accumulate with once daily dosing.
Impaired renal function
The pharmacokinetics of Omeprazole, including systemic bioavailability and elimination rate, are
unchanged in patients with reduced renal function.
Elderly
The metabolism rate of Omeprazole is somewhat reduced in elderly subjects (75-79 years of
age).
Paediatric patients
During treatment with the recommended doses to children from the age of 1 year, similar plasma
concentrations were obtained as compared to adults. In children younger than 6 months,
clearance of Omeprazole is low due to low capacity to metabolise Omeprazole.

Gastric ECL-cell hyperplasia and carcinoids, have been observed in life-long studies in rats
treated with Omeprazole. These changes are the result of sustained hypergastrinaemia
secondary to acid inhibition. Similar findings have been made after treatment with H2-receptor
antagonists, proton pump inhibitors and after partial fundectomy. Thus, these changes are not
from a direct effect of any individual active substance.

Sugar spheres
Hypromellose
Talc
Sodium Hydroxide Pellets
Methacrylic acid ethyl acrylate
Macrogol (Lutrol E400)
Titanium Dioxide
Purified Water
Empty Hard Gelatin Capsule

Not applicable.

Do not store above 30°C.Protect from light

Alu/Alu blister in packs of 7, 14 and 28
Not all pack sizes may be marketed.

Any unused medicinal product or waste material should be disposed of in accordance with local
requirements.