INSTRUCTION

for medical use of the medicinal product

 

OMEPRAZOLE 20 ANANTA

 

Composition:

active substance: omeprazole;

1 capsule* contains omeprazole (as enteric-coated pellets) 20 mg;

excipients: corn starch, sucrose, spherical sugar, light magnesium carbonate, talc, sodium phosphate, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose), methacrylate copolymer (type A), polyethylene glycol (macrogol) 6000, colloidal anhydrous silica, sodium hydroxide, titanium dioxide (E 171).

*Capsule shell contains:

body: titanium dioxide (E 171), gelatin, carmoisine (E 122), tartrazine (E 102), brilliant blue (E 133);

cap: titanium dioxide (E 171), gelatin, erythrosine (E 127).

 

Pharmaceutical form. Capsules.

Basic physical and chemical properties: hard gelatin capsules with a grey body and pink cap; the capsule contents are white or almost white pellets (granules).

 

Pharmacotherapeutic group. Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02BC01.

 

Pharmacological properties.

Pharmacodynamics.

Mechanism of action

Omeprazole is a racemic mixture of two enantiomers that reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the proton pump (PPI) in the parietal cells of the stomach. It acts rapidly and causes controlled reversible inhibition of gastric acid secretion when used once daily.

Omeprazole is a weak base that concentrates and is converted into its active form in the acidic environment of the intracellular canaliculi in parietal cells, where it inhibits the enzyme H⁺/K⁺-ATPase – the acid pump. This effect on the final step of gastric acid formation is dose-dependent and provides highly effective inhibition of both basal and stimulated acid secretion, regardless of the nature of the stimulus.

Pharmacodynamic effects

All observed pharmacodynamic effects can be explained by the action of omeprazole on acid secretion.

Effect on gastric acid secretion

Oral administration of omeprazole once daily causes rapid and effective inhibition of daytime and night-time gastric acid secretion, with maximum effect achieved within 4 days of treatment. In patients with duodenal ulcer, the mean reduction in gastric acidity (approximately 80%) occurs within 24 hours after taking 20 mg of omeprazole; the mean reduction in peak acid output after pentagastrin stimulation is about 70% at 24 hours after omeprazole intake.

Oral administration of 20 mg omeprazole maintains intragastric pH ≥ 3 in patients with duodenal ulcer for an average of 17 hours of the 24-hour period.

As a result of reduced acid secretion and intragastric acidity, omeprazole, depending on the dose, reduces/normalizes the action of acid on the oesophagus in patients with gastroesophageal reflux disease.

Inhibition of acid secretion correlates with the area under the plasma concentration-time curve (AUC) of omeprazole, not with the actual plasma concentration at a given time.

No tachyphylaxis was observed during treatment with omeprazole.

Effect on Helicobacter pylori (H. pylori)

Peptic ulcer disease, including duodenal ulcer and gastric ulcer, is associated with H. pylori. H. pylori is considered a major factor in the development of gastritis and, together with gastric acid, is a crucial factor in the development of peptic ulcer disease. H. pylori is also 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 antimicrobial agents is associated with high healing rates and long-term remission of peptic ulcers.

Dual therapy has been tested and found to be less effective than triple therapy. However, it may be considered in cases where known hypersensitivity precludes the use of any triple combination.

Other effects related to acid inhibition

Slightly increased frequency of gastric glandular cysts has been reported during long-term treatment. These changes are a physiological consequence of acid secretion inhibition; the cysts are benign and reversible.

Reduced gastric acidity caused by any means, including PPIs, increases the number of bacteria normally present in the gastrointestinal tract in the stomach. Treatment with acid-reducing drugs slightly increases the risk of gastrointestinal infections, for example caused by Salmonella and Campylobacter, and in hospitalized patients, possibly also by Clostridium difficile.

During treatment with antisecretory drugs, plasma gastrin concentration increases as a result of decreased hydrochloric acid secretion. Due to decreased hydrochloric acid secretion, chromogranin A (CgA) levels increase. Increased CgA concentration may affect the results of tests for detecting neuroendocrine tumours. Based on available published data, it is suggested that PPI intake should be discontinued 5 to 14 days before planned CgA measurements. This helps avoid falsely elevated CgA levels that could be caused by PPI intake.

During long-term therapy with omeprazole, an increase in the number of enterochromaffin-like (ECL) cells has been observed in some patients (both children and adults), possibly caused by elevated serum gastrin levels. These findings are considered not clinically significant.

Children

In an uncontrolled study in children (aged 1 to 16 years) with severe reflux esophagitis, omeprazole at doses of 0.7 to 1.4 mg/kg improved esophagitis in 90% of cases and significantly reduced reflux symptoms. In a study of children aged 0 to 24 months with a clinically established diagnosis of gastroesophageal reflux disease, treatment with omeprazole at doses of 0.5, 1.0, or 1.5 mg/kg body weight reduced the frequency of vomiting/regurgitation episodes, regardless of dose, by 50% after 8 weeks of treatment.

1. pylori eradication in children

According to a randomized double-blind clinical trial, omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) was safe and effective in treating H. pylori infection in children aged 4 years and older with gastritis. The H. pylori eradication rate was 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin compared to 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, no evidence of any clinical benefit regarding dyspeptic symptoms was obtained. No information is available for children under 4 years of age.

Pharmacokinetics.

Absorption

Omeprazole and omeprazole magnesium salt are acid-labile, therefore they are administered orally as enteric-coated granules in capsules or tablets. Omeprazole absorption is rapid, with peak plasma levels achieved approximately 1–2 hours after dose administration. Absorption of omeprazole occurs in the small intestine and is usually completed within 3–6 hours. Concomitant food intake does not affect bioavailability. The systemic availability (bioavailability) of a single dose of omeprazole is about 40%. After repeated once-daily administration, bioavailability increases to approximately 60%.

Distribution

The apparent volume of distribution in healthy volunteers is approximately 0.3 L/kg body weight. Omeprazole is 97% bound to plasma proteins.

Biotransformation

Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The major part of its metabolism depends on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remaining part depends on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. Due to the high affinity of omeprazole for CYP2C19, competitive inhibition and metabolic interactions between drugs that are substrates for CYP2C19 are possible. However, due to low affinity for CYP3A4, omeprazole is not capable of inhibiting the metabolism of other CYP3A4 substrates. Furthermore, omeprazole has no inhibitory effect on major CYP enzymes.

Approximately 3% of the Caucasian population and 15–20% of the Asian population lack a functional CYP2C19 enzyme and are therefore called "poor metabolizers". In these individuals, omeprazole metabolism is likely mainly catalysed by CYP3A4. After repeated once-daily dosing of 20 mg omeprazole, the AUC in "poor metabolizers" was 5–10 times higher than in subjects with a functional CYP2C19 enzyme ("extensive metabolizers"). Mean peak plasma concentrations were also 3–5 times higher. These findings do not affect the dosing of omeprazole.

Elimination

The plasma elimination half-life of omeprazole is usually less than 1 hour both after single and repeated once-daily dosing. Omeprazole is completely eliminated from plasma between doses, with no tendency to accumulate when used once daily. Almost 80% of an oral dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces via biliary secretion.

Linearity/non-linearity

The AUC of omeprazole increases upon repeated administration. This increase is dose-dependent and leads to a non-linear dose-AUC relationship after repeated administration. This time- and dose-dependence is due to reduced first-pass metabolism and systemic clearance, likely caused by inhibition of CYP2C19 by omeprazole and/or its metabolites (e.g., sulfone).

No effect of omeprazole metabolites on gastric acid secretion has been found.

Special patient groups

Hepatic impairment

The metabolism of omeprazole in patients with hepatic impairment is disturbed, leading to increased AUC. Omeprazole has not shown a tendency to accumulate with once-daily dosing.

Renal impairment

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are unchanged in patients with renal impairment.

Elderly patients

The rate of omeprazole metabolism in elderly patients (75–79 years) is slightly decreased.

Children

During treatment of children aged 1 year and older with recommended doses, similar plasma concentrations were observed as in adult patients. In children under 6 months of age, omeprazole clearance is reduced due to low omeprazole metabolic capacity.

 

Clinical characteristics.

Indications.

Adults

- Treatment of duodenal ulcer;

- Prevention of relapse of duodenal ulcer;

- Treatment of gastric ulcers;

- Prevention of relapse of gastric ulcers;

- In combination with appropriate antibiotics for eradication of Helicobacter pylori (H. pylori) in peptic ulcer disease;

- Treatment of NSAID-associated gastric and duodenal ulcers;

- Prevention of NSAID-associated gastric and duodenal ulcers in at-risk patients;

- Treatment of reflux esophagitis;

- Long-term treatment of patients with healed reflux esophagitis;

- Treatment of symptoms of gastroesophageal reflux disease (GERD);

- Treatment of Zollinger-Ellison syndrome.

Children

Children aged 1 year and older weighing ≥ 10 kg

- Treatment of reflux esophagitis;

- Symptomatic treatment of heartburn and acid regurgitation in GERD.

Children aged 4 years and older and adolescents

- In combination with antibiotics for the treatment of duodenal ulcer caused by pylori.

 

Contraindications.

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any of the excipients.

Omeprazole, like other proton pump inhibitors (PPIs), should not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other forms of interaction").

 

Interaction with other medicinal products and other forms of interaction.

Effect of omeprazole on the pharmacokinetics of other medicinal products

Medicinal products whose absorption is pH-dependent

Reduced gastric acidity during omeprazole treatment may increase or decrease the absorption of drugs whose absorption depends on gastric pH.

Nelfinavir and atazanavir

Plasma concentrations of nelfinavir and atazanavir are reduced when these drugs are co-administered with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated (see section "Contraindications").

Concomitant administration of omeprazole (40 mg once daily) reduced the mean exposure of nelfinavir by approximately 40%, and the mean exposure of the pharmacologically active metabolite M8 was reduced by approximately 75–90%. The interaction may also involve inhibition of CYP2C19.

Concomitant use of omeprazole and atazanavir is not recommended (see section “Precautions for use”). Concomitant administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers reduced atazanavir exposure by 75%. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. Concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers reduced atazanavir exposure by 30% compared to atazanavir 300 mg/ritonavir 100 mg.

Digoxin

Concomitant treatment with omeprazole (20 mg daily) and digoxin increases the bioavailability of digoxin by 10%. Cases of digoxin toxicity have been rarely reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Therapeutic drug monitoring for digoxin should be intensified.

Clopidogrel

Results from a clinical study in healthy volunteers showed a pharmacokinetic/pharmacodynamic (PK/PD) interaction between clopidogrel (loading dose 300 mg followed by 75 mg/day) and omeprazole (80 mg/day), leading to a 46% reduction in exposure to the active metabolite of clopidogrel and a mean 16% reduction in maximum inhibition (adenosine diphosphate (ADP)-induced) of platelet aggregation.

Conflicting data on the clinical implications of this PK/PD interaction in terms of major cardiovascular events have been reported from observational and clinical studies. Thus, concomitant use of omeprazole and clopidogrel should be avoided (see section “Precautions for use”).

Other medicinal products

The absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly reduced, and consequently clinical efficacy may be impaired. Concomitant use with posaconazole and erlotinib should be avoided.

Medicinal products metabolized via CYP2C19

Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme involved in the metabolism of omeprazole itself. Thus, when co-administered with active substances also metabolized by CYP2C19, the metabolism of these substances may be impaired and their systemic exposure increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

Cilostazol

In healthy volunteers, administration of omeprazole 40 mg increased C_max and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively.

Phenytoin

Monitoring of plasma phenytoin concentrations is recommended during the first two weeks after initiating omeprazole treatment and if a phenytoin dose adjustment is made. Monitoring and subsequent dose adjustment of the drug should be performed after omeprazole treatment is discontinued.

Unknown mechanisms of interaction

Saquinavir

Concomitant administration of omeprazole with saquinavir/ritonavir increased plasma concentrations of saquinavir by approximately 70%, which is associated with good tolerability in HIV-infected patients.

Tacrolimus

Increased serum concentrations of tacrolimus have been reported when co-administered with omeprazole. Continuous monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be performed during concomitant use with omeprazole, and the dose of tacrolimus should be adjusted if necessary.

Methotrexate

There are reports of increased methotrexate levels in some patients when co-administered with PPIs. If high-dose methotrexate is required, temporary withdrawal of omeprazole should be considered.

Effect of other medicinal products on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4

Since omeprazole is metabolized by CYP2C19 and CYP3A4, drugs that inhibit CYP2C19, CYP3A4, or both enzymes (such as clarithromycin and voriconazole) may lead to increased serum levels of omeprazole by slowing its metabolism. Concomitant use of voriconazole may lead to more than a doubling of omeprazole exposure. Because high doses of omeprazole are well tolerated, dose adjustment is not required during temporary concomitant use. However, dose adjustment should be considered for patients with severe hepatic impairment and if long-term treatment is indicated.

Inducers of CYP2C19 and/or CYP3A4

Drugs that induce CYP2C19 and/or CYP3A4 or both enzymes (such as rifampicin, St. John's wort) may lead to decreased serum levels of omeprazole by accelerating its metabolism.

 

Precautions for use.

In the presence of any alarm symptom (e.g., significant unintentional weight loss, recurrent vomiting, dysphagia, hematemesis, or melena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with the drug may mask its symptoms and delay the correct diagnosis.

Concomitant use of atazanavir with PPIs is not recommended (see section "Interaction with other medicinal products and other forms of interaction"). If the combination of atazanavir with a PPI is unavoidable, careful clinical monitoring (e.g., viral load) is recommended in combination with increasing the dose of atazanavir to 400 mg with 100 mg ritonavir; the dose of omeprazole should not exceed 20 mg.

Omeprazole, like all drugs that inhibit gastric acid secretion, may reduce the absorption of vitamin B₁₂ (cyanocobalamin) due to hypo- or achlorhydria. This should be considered in patients with cachexia or risk factors for reduced vitamin B₁₂ absorption during long-term therapy.

Omeprazole is an inhibitor of CYP2C19. At the start or end of omeprazole treatment, the potential for interaction with drugs metabolized via CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole (see section "Interaction with other medicinal products and other forms of interaction"). The clinical significance of this interaction is not established. As a precaution, concomitant use of omeprazole and clopidogrel should be avoided.

In patients taking PPIs, including omeprazole, for at least 3 months, significant hypomagnesemia may occur (in most cases of hypomagnesemia, patients had been using the drug for about 1 year). Hypomagnesemia may be suspected based on serious manifestations such as fatigue, muscle spasms, convulsions, delirium, dizziness, ventricular arrhythmia. However, it should be kept in mind that in some cases the manifestations may be masked, hindering timely recognition of this complication. In most patients, manifestations of hypomagnesemia resolve and the condition normalizes after magnesium supplementation and discontinuation of the PPI.

In patients requiring long-term PPI treatment, and patients concomitantly taking digoxin or other drugs that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting PPI treatment and periodically during treatment.

Omeprazole may cause severe skin reactions. Symptoms may include skin redness, blisters, and rash. If an allergic reaction occurs, treatment should be discontinued and medical help sought.

Severe cutaneous adverse reactions (SCARs) have been reported with omeprazole, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal.

Proton pump inhibitor therapy, especially at high doses and for long durations (> 1 year), may be associated with a small increased risk of fractures of the spine, wrist, and hip, mainly in elderly individuals and patients with additional risk factors. According to observational studies, PPIs increase the overall risk of fractures by 10–40%. Patients at risk of progressive osteoporosis or osteoporotic fracture should be advised appropriate clinical monitoring according to current clinical guidelines for this condition and should consume adequate amounts of vitamin D and calcium.

Subacute cutaneous lupus erythematosus (SCLE)

PPI use may occasionally cause subacute cutaneous lupus erythematosus. If skin manifestations occur, especially in areas exposed to sunlight, and if accompanied by arthralgia, medical advice should be sought immediately and discontinuation of omeprazole should be considered. A history of subacute cutaneous lupus erythematosus following PPI use may increase the risk of SCLE with other PPIs.

Renal impairment

Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking omeprazole and may occur at any time during omeprazole therapy (see section "Adverse reactions"). Acute tubulointerstitial nephritis may progress to renal failure. If ATIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.

Effect on laboratory tests

During treatment with antisecretory drugs, plasma gastrin concentration increases as a result of decreased hydrochloric acid secretion. Due to decreased hydrochloric acid secretion, chromogranin A (CgA) levels increase. Increased CgA concentration may affect the results of tests for detecting neuroendocrine tumors. To prevent such an effect, PPI intake should be discontinued 5 days before measuring CgA levels (see section "Pharmacodynamics"). If CgA and gastrin levels have not returned to the reference range after initial measurements, measurements should be repeated 14 days after discontinuing PPI treatment.

For the treatment of chronic diseases, the drug should not be used in children for longer than recommended.

The drug contains sucrose (as part of sugar granules) as an excipient, therefore patients with established intolerance to certain sugars should consult a doctor before taking this medicinal product.

PPI treatment slightly increases the risk of gastrointestinal infections caused by Salmonella and Campylobacter, and in hospitalized patients, possibly also Clostridium difficile (see section "Pharmacodynamics").

As with any long-term treatment, especially if it exceeds 1 year, the patient's condition should be monitored.

The medicinal product contains carmoisine (E 122) and tartrazine (E 102), which may cause allergic reactions.

Pregnancy and lactation.

Pregnancy

Results from three prospective epidemiological studies (more than 1000 outcomes) indicate no adverse effect of omeprazole on pregnancy or the health of the fetus/newborn child, therefore the drug may be used during pregnancy.

Breastfeeding

Omeprazole passes into breast milk, but is unlikely to affect the child when used at therapeutic doses.

Fertility

Preclinical studies (animal studies) with the racemic mixture of oral omeprazole indicate no effect on fertility.

 

Effects on ability to drive and use machines

It is unlikely that the medicinal product affects the ability to drive vehicles or operate other machinery. Adverse reactions such as dizziness and visual disturbances are possible (see section "Adverse reactions"). If these disorders occur, patients should not drive or operate other machinery.

 

Method of administration and dosage.

Dosage

Adults

Treatment of duodenal ulcers

The recommended dose for patients with active duodenal ulcer is 20 mg omeprazole once daily. In most patients, duodenal ulcer heals within 2 weeks. For patients whose ulcer does not fully heal after the initial course, further treatment for 2 weeks is recommended. For patients with a poor therapeutic response, the recommended dose is 40 mg omeprazole daily; ulcer healing is usually achieved within 4 weeks.

Prevention of relapse of duodenal ulcers

For the prevention of duodenal ulcer relapse in patients with negative H. pylori test or when H. pylori eradication is not possible, the recommended dose is 20 mg omeprazole once daily. For some patients, a daily dose of 10 mg* may be sufficient. If treatment is ineffective, the dose may be increased to 40 mg.

Treatment of gastric ulcers

The recommended dose is 20 mg omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. For patients whose ulcer does not fully heal after the initial course, further treatment for 4 weeks is recommended. In severe cases or in cases of relapse, 40 mg omeprazole once daily is recommended; healing is usually achieved within 8 weeks.

Prevention of relapse of gastric ulcers

For the prevention of relapse in patients with gastric ulcer and insufficient response to treatment, the recommended dose is 20 mg omeprazole once daily. If necessary, the dose may be increased to 40 mg omeprazole once daily.

Eradication of H. pylori in peptic ulcer disease

For eradication of H. pylori, when choosing antibacterial drugs, individual drug tolerance, relevant national and local characteristics, and treatment guidelines should be considered:

- Omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg twice daily for 1 week, or

- Omeprazole 20 mg + clarithromycin 250 mg (500 mg if needed) + metronidazole 400 mg (500 mg or tinidazole 500 mg if needed) twice daily for 1 week, or

- Omeprazole 40 mg once daily + amoxicillin 500 mg + metronidazole 400 mg (500 mg or tinidazole 500 mg if needed) three times daily for 1 week.

With each regimen, if the patient remains positive for H. pylori, therapy may be repeated.

Treatment of NSAID-associated gastric and duodenal ulcers

For the treatment of gastric and duodenal ulcers associated with NSAID use, the recommended dose is 20 mg omeprazole once daily. In most patients, the ulcer heals within 4 weeks. In patients who are not fully healed after the initial course, healing usually occurs within an additional 4-week treatment period.

Prevention of NSAID-associated gastric and duodenal ulcers in at-risk patients

For the prevention of NSAID-associated gastric and duodenal ulcers in at-risk patients (age over 60 years, history of gastric or duodenal ulcer, history of upper gastrointestinal bleeding), the recommended dose is 20 mg omeprazole once daily.

Treatment of reflux esophagitis

The recommended dose is 20 mg omeprazole once daily. In most patients, healing occurs within 4 weeks. For patients whose ulcer does not fully heal after the initial course, further treatment for an additional 4 weeks is recommended. For patients with severe esophagitis, 40 mg omeprazole daily is recommended; healing usually occurs within 8 weeks.

Long-term treatment of patients with healed reflux esophagitis

For long-term treatment of patients with GERD, the recommended dose is 10 mg* omeprazole once daily. If necessary, the dose may be increased to 20–40 mg omeprazole once daily.

Treatment of GERD symptoms

For the treatment of GERD symptoms, the recommended dose is 20 mg omeprazole once daily. A dose of 10 mg* may be sufficient for some patients; the dose should be adjusted individually. If the desired result is not achieved after 4 weeks of treatment with omeprazole 20 mg daily, the patient should be further investigated.

Treatment of Zollinger-Ellison syndrome

For patients with Zollinger-Ellison syndrome, the dose should be individualized. Treatment continues until clinical manifestations of the disease disappear. The recommended initial dose is 60 mg omeprazole once daily. Monitoring of more than 90% of patients with severe disease and insufficient response to other treatments has shown the effectiveness of maintenance therapy at doses of 20–120 mg daily. Daily doses above 80 mg should be divided and administered in two doses.

Children

Children aged 1 year and older weighing ≥ 10 kg

Treatment of reflux esophagitis

Symptomatic treatment of heartburn and acid regurgitation in GERD

 

Dosage recommendations:

Age	Body weight	Dosage
≥ 1 year	10–20 kg	10 mg* once daily. If necessary, the dose may be increased to 20 mg once daily.
≥ 2 years	> 20 kg	20 mg once daily. If necessary, the dose may be increased to 40 mg once daily.

Treatment of reflux esophagitis: duration of treatment is 4–8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in GERD: duration of treatment is 2–4 weeks. If the desired result is not achieved after 2–4 weeks, the patient should be further investigated.

Children aged 4 years and older and adolescents

Treatment of duodenal ulcer caused by H. pylori

The choice of appropriate combination therapy should follow official national, regional, and local bacterial resistance patterns. The duration of treatment (from 7 to 14 days) and appropriate use of antibacterial drugs should also be considered. Treatment should be carried out under medical supervision.

 

Dosage recommendations:

Body weight	Dosage
15–30 kg	Combination with two antibiotics: Omeprazole 10 mg* + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. Take together twice daily for 1 week.
31–40 kg	Combination with two antibiotics: Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. Take together twice daily for 1 week.
> 40 kg	Combination with two antibiotics: Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. Take together twice daily for 1 week.

* If a 10 mg dose is necessary, use the appropriate dosage strength.

 

Special population

Renal impairment

No dose adjustment is necessary for patients with renal impairment (see section "Pharmacokinetics").

Hepatic impairment

For patients with hepatic impairment, a daily dose of 10*–20 mg is sufficient (see section "Pharmacokinetics").

Elderly patients

No dose adjustment is necessary for elderly patients (see section "Pharmacokinetics").

Method of administration

Capsules should preferably be taken in the morning, before a meal, without damaging the capsule (capsules should not be chewed or broken), and swallowed with a small amount of water.

For patients with swallowing difficulties and for children who can drink or swallow semi-solid food

The capsules can be opened and the contents swallowed directly with half a glass of water, or mixed with a weakly acidic drink such as fruit juice or apple puree, or still water. The mixture must be taken immediately after preparation or within 30 minutes. The mixture should be stirred before taking and followed by half a glass of water.

Alternatively, patients may suck the capsule and swallow the granules with half a glass of water. The enteric-coated granules should not be chewed.

 

Children.

The medicinal product is used in children aged 1 year and older weighing more than 10 kg, as prescribed by a doctor, for the treatment of reflux esophagitis, symptomatic treatment of heartburn and acid regurgitation in GERD, and in children aged 4 years and older for the treatment of duodenal ulcer caused by H. pylori, under medical supervision.

 

Overdose.

Data on the effects of omeprazole overdose in humans are very limited. Doses up to 560 mg of omeprazole have been described in the literature; there are isolated reports of a single oral dose of 2400 mg of omeprazole (120 times higher than the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache have been reported. Apathy, depression, and confusion have also been reported in isolated cases.

However, all these symptoms were transient; no serious consequences have been reported. The elimination rate of the drug did not change (first-order kinetics) with increasing dose. If necessary, symptomatic treatment should be given.

 

Adverse reactions.

Safety profile summary

The most common adverse reactions (1–10% of patients) are headache, abdominal pain, constipation, diarrhea, flatulence, and nausea/vomiting.

Severe cutaneous adverse reactions (SCARs) have been reported with omeprazole, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) (see section “Precautions for use”).

Below are the adverse reactions that have been identified or suspected during clinical trials or post-marketing use of omeprazole. They were found not to be dose-dependent. Adverse reactions are listed by system organ class. Frequencies are defined as: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency unknown (cannot be estimated from available information).

Blood and lymphatic system disorders: rare: leukopenia, thrombocytopenia; very rare: agranulocytosis, pancytopenia.

Immune system disorders: rare: hypersensitivity reactions including fever, angioedema, and anaphylactic reactions/shock.

Metabolism and nutrition disorders: rare: hyponatremia; frequency unknown: hypomagnesaemia; severe hypomagnesaemia may lead to hypocalcaemia; hypomagnesaemia associated with hypokalaemia.

Psychiatric disorders: uncommon: insomnia; rare: agitation, confusion, depression; very rare: aggression, hallucinations.

Nervous system disorders: common: headache; uncommon: dizziness, paraesthesia, drowsiness; rare: taste disturbance.

Eye disorders: rare: blurred vision (see section "Effects on ability to drive and use machines").

Ear and labyrinth disorders: uncommon: vertigo (see section "Effects on ability to drive and use machines").

Respiratory, thoracic and mediastinal disorders: rare: bronchospasm.

Gastrointestinal disorders: common: abdominal pain, constipation, diarrhea, flatulence, nausea/vomiting, fundic gland polyps (benign); rare: dry mouth, stomatitis, gastrointestinal candidiasis; frequency unknown: microscopic colitis.

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, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS); very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency unknown: subacute cutaneous lupus erythematosus (see section “Precautions for use”).

Musculoskeletal and connective tissue disorders: uncommon: fractures of the hip, wrist, or spine; rare: arthralgia, myalgia; very rare: muscle weakness.

Renal and urinary disorders: rare: tubulointerstitial nephritis (with possible progression to renal failure).

Reproductive system and breast disorders: very rare: gynaecomastia.

General disorders and administration site conditions: uncommon: malaise, peripheral oedema; rare: increased sweating.

Children

The safety of omeprazole was assessed in 310 children aged 0 to 16 years with acid-related diseases. Limited data are available on the long-term safety of the drug in 46 children who received maintenance therapy with omeprazole during treatment of severe erosive esophagitis for 749 days. The adverse reaction profile was similar to that in adults for both short-term and long-term treatment. No data are available on the long-term or remote effects of omeprazole treatment on puberty and growth.

 

Adverse Reactions Reporting

Adverse reactions reporting after the registration of a medicinal product is of great importance. It enables the monitoring of the benefit/risk ratio associated with the use of the medicinal product. Healthcare professionals, pharmacists, as well as patients or their legal representatives, should report all suspected adverse reactions and cases of lack of efficacy of the medicinal product via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

 

Shelf life. 3 years.

 

Storage conditions.

Store in the original package at a temperature not exceeding 30 °C.

Keep out of reach of children.

 

Packaging. 10 capsules in a blister, 10 blisters in a box.

 

Terms of dispensing. On prescription.

 

Date of last update.

08.04.2024