Omeprazole ananta

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEPRAZOLE ANANTA (OME PRAZOLEANANTA)

Composition:

Active substance: omeprazole;

1 capsule contains omeprazole (in the form of enteric-coated pellets) 20 mg;

Excipients:

in the composition of omeprazole enteric-coated pellets: mannite (E 421), calcium carbonate, sodium hydrogen phosphate dihydrate, sodium lauryl sulfate, sugar, povidone, sodium methylparaben (E 219), sodium propylparaben (E 217), hypromellose, methacrylate copolymer dispersion, sodium hydroxide, diethyl phthalate, talc, titanium dioxide (E 171), polysorbate 80, purified water;

in the composition of neutral pellets: corn starch, sugar, anhydrous lactose; gelatin.

Pharmaceutical form. Modified-release capsules.

Main physicochemical properties: hard gelatin capsules with a pink cap and transparent body, containing white pellets.

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

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action.

Omeprazole, a racemic mixture of two enantiomers, reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the proton pump in parietal cells. It acts rapidly and effectively suppresses acid secretion with once-daily dosing.

Omeprazole is a weak base that accumulates and is converted into its active form in the acidic environment of the intracellular canaliculi of parietal cells, where it inhibits the enzyme H⁺K⁺-ATPase—the acid pump. This effect on the final stage of gastric acid production is dose-dependent and results in highly effective suppression of both basal and stimulated acid secretion, regardless of the nature of the stimulus.

Pharmacodynamic effects.

All observed pharmacodynamic effects can be explained by omeprazole's effect on acid secretion.

Effect on gastric acid secretion.

Oral administration of 20 mg omeprazole once daily results in rapid and effective inhibition of daytime and nighttime gastric acid secretion, with maximum effect achieved within 4 days of treatment. In patients with duodenal ulcer, mean reduction in gastric acidity is approximately 80% over 24 hours after a 20 mg dose of omeprazole. The mean reduction in peak acid output following pentagastrin stimulation is about 70% at 24 hours after omeprazole administration.

Oral administration of 20 mg omeprazole maintains intragastric pH ≥3 for an average of 17 hours out of 24 hours in patients with duodenal ulcer. Due to reduced acid secretion and intragastric acidity, omeprazole, in a dose-dependent manner, reduces/normalizes acid exposure of the esophagus in patients with gastroesophageal reflux disease. Inhibition of acid secretion correlates with the area under the plasma concentration–time curve (AUC) of omeprazole, rather than with the instantaneous plasma concentration.

No tachyphylaxis has been observed during omeprazole treatment.

Effect on Helicobacter pylori (H. pylori).

Peptic ulcer disease is associated with H. pylori, including duodenal and gastric ulcers. H. pylori is considered the primary causative factor in the development of gastritis. H. pylori, together with gastric acid, are the main factors in the pathogenesis of peptic ulcer disease. H. pylori is the main cause of atrophic gastritis, which is associated with an increased risk of gastric cancer.

Eradication of H. pylori using omeprazole in combination with antimicrobial agents is associated with faster symptom relief, high mucosal healing rates, and long-term remission of peptic ulcer disease.

Other effects related to acid suppression.

During long-term treatment, a slightly increased frequency of gastric fundic gland polyps has been reported. These changes are a physiological consequence of sustained acid suppression, are benign, and reversible.

Reducing gastric acidity by any means, including proton pump inhibitors, increases the number of bacteria normally present in the gastrointestinal tract. Treatment with acid-reducing agents may lead to a slightly increased risk of gastrointestinal infections, such as those caused by Salmonella, Campylobacter, and Clostridium difficile, particularly in hospitalized patients.

Pediatric use.

In an uncontrolled study involving children (aged 1 to 16 years) with severe erosive esophagitis, omeprazole at doses of 0.7–1.4 mg/kg improved esophagitis in 90% of patients and significantly reduced reflux symptoms. In a blinded, comparator-free study involving children aged 0 to 24 months with diagnosed gastroesophageal reflux disease, treatment with omeprazole at doses of 0.5 mg/kg, 1.0 mg/kg, and 1.5 mg/kg resulted in a 50% reduction in the frequency of vomiting/regurgitation episodes after 8 weeks of treatment, regardless of dose.

Eradication of H. pylori in children.

In a randomized, double-blind clinical trial (the Héliot study), it was concluded that 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) in the omeprazole + amoxicillin + clarithromycin group compared to 9.4% (3/32 patients) in the amoxicillin + clarithromycin group. However, there was no evidence of clinical benefit regarding dyspeptic symptoms. This study provides no information for children under 4 years of age.

Pharmacokinetics.

Absorption.

Omeprazole is rapidly absorbed, with peak plasma concentrations reached approximately 1–2 hours after dosing. Absorption occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake does not affect bioavailability. Systemic availability (bioavailability) of omeprazole after a single oral dose is approximately 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 plasma protein binding is 97%.

Metabolism.

Omeprazole is completely metabolized by the cytochrome P450 system. The majority of omeprazole metabolism depends on the CYP2C19 isoenzyme, which is responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. The remaining portion depends on another specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, there is potential for competitive inhibition and metabolic interactions with other CYP2C19 substrates. However, due to its low affinity for CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. Furthermore, omeprazole does not inhibit major CYP enzymes.

Approximately 3% of individuals of Caucasian ethnicity and 15–20% of individuals of Asian ethnicity lack functional CYP2C19 enzyme. In these individuals, omeprazole metabolism is likely primarily catalyzed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5–10 times higher in poor metabolizers than in individuals with functional CYP2C19 (extensive metabolizers). Mean peak plasma concentrations were also 3–5 times higher. These observations have no relevance for omeprazole dosing.

Elimination.

The terminal half-life of omeprazole in plasma is typically less than 1 hour, both after single and multiple once-daily oral doses. Omeprazole is completely eliminated from plasma between doses, with no tendency for accumulation when administered once daily. Approximately 80% of an oral dose of omeprazole is excreted in urine as metabolites, and the remainder in feces, primarily via bile.

With repeated dosing, the AUC of omeprazole increases. This increase is dose-dependent and results in a non-linear relationship between dose and AUC after repeated administration. This time- and dose-dependency is related to reduced presystemic metabolism and systemic clearance, possibly due to omeprazole and/or its metabolites (e.g., sulfone) inhibiting the CYP2C19 enzyme.

No effect of metabolites on gastric acid secretion has been observed.

Special populations.

Hepatic impairment.

In patients with impaired liver function, omeprazole metabolism is altered, leading to increased AUC. Omeprazole showed no tendency for accumulation when administered once daily.

Renal impairment.

The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are not altered in patients with reduced renal function.

Elderly patients.

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

Children.

During treatment with recommended doses, plasma concentrations in children aged 1 year and older are similar to those in adults. In children under 6 months of age, omeprazole clearance is reduced due to limited metabolic capacity.

Clinical characteristics.

Indications.

In adults:

• treatment and prevention of recurrence of duodenal ulcer and benign gastric ulcer, including those associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs);
• prevention of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients at risk;
• eradication of Helicobacter pylori (H. pylori) in peptic ulcer disease in combination with appropriate antibiotics;
• treatment of gastroesophageal reflux disease, including reflux esophagitis;
• treatment of Zollinger–Ellison syndrome.

In children

Children aged 1 year and older, with body weight over 10 kg:

• treatment of reflux esophagitis;
• symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Children aged 4 years and older:

• treatment of duodenal ulcer caused by H. pylori, in combination with antibiotics.

Contraindications.

Hypersensitivity to omeprazole, substituted benzimidazoles, or to any excipient. Omeprazole, like other proton pump inhibitors (PPIs), should not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Effect of omeprazole on the pharmacokinetics of other medicinal products.

Medicinal products whose absorption depends on gastric pH.

Suppression of gastric secretion during treatment with omeprazole and other PPIs may reduce or increase the absorption of medicinal products whose absorption is pH-dependent. As with other agents that reduce intragastric acidity, absorption of drugs such as ketoconazole, itraconazole, and erlotinib may be decreased, whereas absorption of drugs such as digoxin may be increased during omeprazole treatment. Concomitant administration of omeprazole (20 mg once daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10% (up to 30% in two out of ten subjects).

Nelfinavir, atazanavir.

Plasma levels of nelfinavir and atazanavir are reduced when co-administered with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated. Co-administration of omeprazole (40 mg once daily) with nelfinavir reduced mean nelfinavir exposure by approximately 40%, and mean exposure to its pharmacologically active metabolite M8 decreased by approximately 75–90%. This interaction may also be due to inhibition of CYP2C19 activity.

Concomitant use of omeprazole and atazanavir is not recommended. Co-administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a 75% reduction in atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Co-administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers resulted in approximately a 30% reduction in atazanavir exposure compared to atazanavir 300 mg/ritonavir 100 mg.

Digoxin.

Concomitant treatment with omeprazole (20 mg once daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10%. Rare cases of digoxin-induced toxicity have been reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. Patients receiving concomitant digoxin should be closely monitored by a physician.

Clopidogrel.

Clinical studies in healthy volunteers have demonstrated a pharmacokinetic/pharmacodynamic (PK/PD) interaction between clopidogrel (loading dose 300 mg followed by 75 mg/day) and omeprazole (80 mg daily), resulting in a 46% reduction in exposure to the active metabolite of clopidogrel and a mean 16% reduction in maximum inhibition (ADP-induced) of platelet aggregation.

Conflicting data on the clinical significance of this PK/PD interaction regarding major cardiovascular events have been reported in observational and clinical studies. Therefore, concomitant use of omeprazole and clopidogrel should be avoided.

Other medicinal products.

Absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly reduced, and thus clinical efficacy may be diminished. Concomitant use with posaconazole and erlotinib should be avoided.

Medicinal products metabolized by CYP2C19.

Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme responsible for omeprazole metabolism. Therefore, metabolism of concomitantly administered medicinal products that are also metabolized by CYP2C19 may be reduced, and systemic exposure to these agents may increase. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.

In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg, maintenance dose 75 mg daily) and omeprazole (80 mg daily orally, i.e., a dose four times higher than the standard daily dose), resulting in a mean 46% reduction in exposure to the active metabolite of clopidogrel and a mean 16% reduction in maximum inhibitory effect (ADP-induced) on platelet aggregation. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

Cilostazol.

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

Phenytoin.

Plasma phenytoin concentration monitoring is recommended during the first two weeks after initiation of omeprazole treatment and if phenytoin dose adjustment has been made. Monitoring and further dose adjustments should continue after discontinuation of omeprazole.

Unknown mechanism of interaction.

Saquinavir.

Concomitant use of omeprazole with saquinavir/ritonavir resulted in an increase in saquinavir plasma levels by approximately 70%, which was associated with acceptable tolerability in HIV-infected patients.

Tacrolimus.

Increased serum levels of tacrolimus have been reported with concomitant use of omeprazole. Intensified monitoring of tacrolimus concentration and renal function (creatinine clearance) is required, and dose adjustment of tacrolimus may be necessary.

Methotrexate.

Elevated methotrexate levels have been reported in some patients receiving concomitant proton pump inhibitors. In cases where high-dose methotrexate therapy is required, temporary discontinuation 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 enzymes, medicinal products known to inhibit the activity of CYP2C19 or CYP3A4, or both enzymes (such as clarithromycin and voriconazole), may increase omeprazole plasma levels due to reduced metabolic rate. Concomitant use of voriconazole resulted in more than a twofold increase in omeprazole exposure. Since high doses of omeprazole are generally well tolerated, dose adjustment of omeprazole is usually not required. However, dose adjustment should be considered in patients with severe hepatic impairment and in cases of long-term treatment.

Omeprazole is also partially metabolized by CYP3A4, but does not inhibit this enzyme. Therefore, omeprazole does not affect the metabolism of medicinal products metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide.

Inducers of CYP2C19 and/or CYP3A4.

Medicinal products known to induce the activity of CYP2C19 or CYP3A4, or both enzymes (such as rifampicin and St. John's wort), may reduce omeprazole plasma levels due to accelerated metabolism.

Special precautions for use

In the presence of any alarming symptom (e.g., significant unintentional weight loss, frequent vomiting, dysphagia, vomiting with blood or melena), and when gastric ulcer has been diagnosed or is suspected, malignancy should be ruled out, as treatment with this medicinal product may mask symptoms and delay correct diagnosis.

Concomitant use of atazanavir with proton pump inhibitors is not recommended (see section "Interaction with other medicinal products and other forms of interaction"). If co-administration of atazanavir with a proton pump inhibitor cannot be avoided, careful clinical monitoring (e.g., viral load) is recommended, together with an increased dose of atazanavir to 400 mg with 100 mg ritonavir; the dose of omeprazole should not exceed 20 mg.

Omeprazole, like all medicinal products that suppress gastric acid secretion, may reduce 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 initiation or discontinuation of omeprazole treatment, potential interactions with medicinal products metabolized by 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 relevance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.

In patients receiving proton pump inhibitors, including omeprazole, for at least three months, significant hypomagnesemia may occur (in most cases, patients had been taking the drug for about one year). Hypomagnesemia may be suspected based on serious manifestations such as fatigue, muscle spasms, delirium, vertigo, and ventricular arrhythmias. However, it should be noted that symptoms may sometimes be masked, which may delay timely recognition of this complication. In most patients, symptoms of hypomagnesemia resolve and levels normalize after magnesium supplementation and discontinuation of proton pump inhibitors.

In patients requiring long-term treatment or those receiving PPIs together with digoxin or medicinal products that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be measured before starting PPI therapy and periodically during treatment, if possible.

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 advice sought.

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

Prolonged reduction in gastric acidity may lead to increased bacterial colonization of the gastrointestinal tract.

Treatment with proton pump inhibitors may lead to a slightly increased risk of gastrointestinal infections caused by Salmonella, Campylobacter, and Clostridium difficile in hospitalized patients.

Therapy with proton pump inhibitors, particularly at high doses and for prolonged durations (>1 year), may be associated with a small increase in the risk of fractures of the spine, wrist, and hip, primarily in elderly patients and those 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 offered appropriate clinical monitoring according to current clinical guidelines for this condition and should receive adequate intake of vitamin D and calcium.

Renal function 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.

Subacute cutaneous lupus erythematosus (SCLE)

Use of proton pump inhibitors may be associated with very rare cases of SCLE. If skin lesions occur, particularly on sun-exposed areas, and are accompanied by arthralgia, the patient should seek immediate medical attention, and the healthcare provider should consider discontinuation of omeprazole. The risk of developing SCLE increases with subsequent use of other proton pump inhibitors after a previous episode of SCLE associated with a proton pump inhibitor.

Effect on diagnostic test results

During treatment with antisecretory medicinal products, serum gastrin levels may increase due to reduced gastric acid secretion. Reduced gastric acid secretion leads to increased levels of chromogranin A (CgA). Elevated CgA levels may interfere with diagnostic tests for neuroendocrine tumors.

Published data indicate that PPIs should be discontinued 5–14 days before measuring CgA levels. This prevents misinterpretation of CgA levels after PPI use and allows levels to return to the reference range. If chromogranin A and gastrin levels do not return to normal after initial testing, measurements should be repeated 14 days after discontinuation of proton pump inhibitor therapy.

Increased numbers of enterochromaffin-like (ECL) cells may be associated with elevated serum gastrin levels, which may occur in some patients (both adults and children) during long-term omeprazole treatment. These findings are considered to have no clinical significance.

For the treatment of chronic conditions, children should not be treated longer than recommended.

During long-term treatment, especially longer than 1 year, the patient should remain under medical supervision.

The medicinal product contains lactose and sucrose. In case of intolerance to certain sugars, consult a physician before taking this medicinal product.

The medicinal product contains sodium methylparahydroxybenzoate (E 219) and sodium propylparahydroxybenzoate (E 217), which may cause allergic reactions (possibly delayed).

Use during pregnancy or breastfeeding

Results from three prospective epidemiological studies (over 1000 outcomes) indicate no adverse effects of omeprazole on pregnancy or fetal/neonatal health. Omeprazole may be used during pregnancy.

Omeprazole passes into breast milk, but is unlikely to affect the infant when used at therapeutic doses. If omeprazole use is necessary during breastfeeding, consult a physician.

Ability to influence reaction speed when driving or operating machinery

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

Method of Administration and Dosage.

Dosage for Adults.

Treatment and prevention of duodenal ulcer and benign gastric ulcer, including those associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs).

The recommended dose for patients with duodenal ulcer is 20 mg of omeprazole once daily. In most patients, duodenal ulcer heals within 2 weeks. For patients who do not achieve complete healing after the initial course, further treatment for 2 weeks is recommended. In severe or relapsing cases, 40 mg of omeprazole daily is recommended, and healing is usually achieved within 4 weeks.

For prevention of recurrence of duodenal ulcer in patients with a negative H. pylori test or in cases where eradication of H. pylori is not possible, the recommended dose is 20 mg of omeprazole once daily. For some patients, a daily dose of 10 mg may be sufficient (use the drug in the corresponding dosage strength). If the therapeutic response is inadequate, the dose may be increased to 40 mg.

For treatment of gastric ulcer, the recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. Patients who do not achieve complete healing after the initial course are recommended further treatment for 4 weeks. In severe or relapsing cases, 40 mg of omeprazole daily is recommended, and healing is usually achieved within 8 weeks.

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

For treatment of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs, the recommended dose is 20 mg of omeprazole once daily. In most patients, healing occurs within 4 weeks. Patients who do not achieve complete healing after the initial course are recommended further treatment for 4 weeks.

For prevention of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs in patients at increased risk (age >60, history of gastric or duodenal ulcers, upper gastrointestinal bleeding), the recommended dose is 20 mg of omeprazole once daily.

Eradication of H. pylori in peptic ulcer disease.

When selecting antibacterial agents for H. pylori eradication, individual drug tolerability should be considered, and national, regional, and local treatment guidelines should be followed.

• Omeprazole 20 mg + clarithromycin 500 mg + amoxicillin 1000 mg twice daily for 1 week, or
• Omeprazole 20 mg + clarithromycin 250 mg (if necessary, 500 mg) + metronidazole 400 mg (if necessary, 500 mg or tinidazole 500 mg) twice daily for 1 week, or
• Omeprazole 40 mg once daily + amoxicillin 500 mg + metronidazole 400 mg (if necessary, 500 mg or tinidazole 500 mg) three times daily for 1 week.

Treatment of gastroesophageal reflux disease, including reflux esophagitis.

The recommended dose is 20 mg of omeprazole once daily. In most patients, recovery occurs within 4 weeks. Patients who do not achieve complete recovery after the initial course are recommended further treatment for 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with recovery usually achieved within 8 weeks.

For long-term treatment of patients with gastroesophageal reflux disease, the recommended dose is 10 mg (use the drug in the corresponding dosage strength) of omeprazole once daily. If necessary, the dose may be increased to 20–40 mg of omeprazole once daily.

For treatment of symptoms of gastroesophageal reflux disease, the recommended dose is 20 mg of omeprazole once daily. A dose of 10 mg (use the drug in the corresponding dosage strength) may be sufficient for some patients; dosage should be adjusted individually. If the desired effect is not achieved after 4 weeks of treatment with 20 mg of omeprazole daily, the patient should be further evaluated.

Treatment of Zollinger – Ellison Syndrome.

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

Dosage for Children.

Children aged 1 year and older, with body weight ≥10 kg.

Treatment of reflux esophagitis.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease.

Table 1

Age	Body weight	Dosage
≥ 1 year	10–20 kg	10 mg (administer the drug at the appropriate dosage) 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: treatment duration is 4–8 weeks.

Symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease: treatment duration is 2–4 weeks. If the desired result has not been achieved after 2–4 weeks, the patient should be further examined.

Children aged 4 years and older.

Treatment of duodenal ulcer caused by H. pylori.

The choice of appropriate combination therapy should follow official national, regional, and local guidelines regarding bacterial resistance. The duration of treatment (from 7 to 14 days) and proper use of antibacterial agents should also be considered. Treatment must be conducted under medical supervision.

Table 2

Body weight	Dosage
15–30 kg	Omeprazole 10 mg (use the drug in the appropriate dosage) + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. Take the drugs together twice daily for 1 week
31–40 kg	Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. Take the drugs together twice daily for 1 week.
> 40 kg	Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. Take the drugs together twice daily for 1 week.

For patients with swallowing difficulties and for children who can drink or swallow semi-solid food. Capsules can be opened and the contents swallowed directly with half a glass of water, or mixed in a mildly acidic liquid, such as any fruit juice, apple puree, or unsalted water. This mixture should be taken immediately after preparation or within 30 minutes. Before administration, the mixture should be shaken and followed by half a glass of water. Do not use milk or carbonated water. The capsule contents (enteric-coated pellets) must not be chewed.

Special patient groups.

Renal impairment. Dose adjustment is not required in patients with renal impairment (see section "Pharmacokinetics").

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

Elderly patients (>65 years of age). Dose adjustment is not required in elderly patients (see section "Pharmacokinetics").

It is recommended to take capsules in the morning, preferably before meals, without damaging the capsule (capsules should not be chewed or crushed), and with a small amount of water.

Children.

The drug is indicated for children aged 1 year and older, with body weight exceeding 10 kg, as prescribed by a physician for the treatment of reflux esophagitis and symptomatic relief of heartburn and acid regurgitation associated with gastroesophageal reflux disease (GERD), and for children aged 4 years and older for the treatment of duodenal ulcer associated with H. pylori, under medical supervision.

Overdose.

Human data on omeprazole overdose are very limited. Scientific literature has reported cases of omeprazole doses up to 560 mg, and isolated reports of single oral doses of 2400 mg omeprazole (120 times higher than the usual recommended clinical dose). Symptoms reported include nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache. In isolated cases, lethargy, depression, and confusion have also been reported.

The described symptoms are transient in nature. Elimination kinetics remain first-order, unchanged with increasing dose. If treatment is required, it should be symptomatic.

Adverse reactions.

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

Severe skin adverse reactions (SCAR) have been reported with the use of 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 "Special precautions").

The following adverse reactions have been identified or suspected during clinical trials of omeprazole or post-marketing use. Adverse reactions are classified by organ system or affected systems.

Blood and lymphatic system disorders: leucopenia, thrombocytopenia, agranulocytosis, pancytopenia.

Immune system disorders: hypersensitivity reactions, such as fever, angioneurotic oedema, and anaphylactic reaction/shock.

Metabolism and nutrition disorders: hyponatraemia, hypomagnesaemia, severe hypomagnesaemia which may lead to hypocalcaemia. Hypomagnesaemia may also be associated with hypokalaemia.

Psychiatric disorders: insomnia, agitation, confusion, depression, aggression, hallucinations.

Nervous system disorders: headache, dizziness, paraesthesia, somnolence, taste disturbance.

Eye disorders: blurred vision.

Ear and labyrinth disorders: tinnitus, vertigo.

Respiratory, thoracic and mediastinal disorders: bronchospasm.

Gastrointestinal disorders: abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, gastric fundic gland polyps, dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis.

Hepatobiliary disorders: increased liver enzyme levels, hepatitis with or without jaundice, hepatic failure, encephalopathy in patients with pre-existing liver disease.

Skin and subcutaneous tissue disorders: dermatitis, pruritus, rash, urticaria, alopecia, photosensitivity, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), polymorphic erythema, Stevens–Johnson syndrome, toxic epidermal necrolysis (TEN), subacute cutaneous lupus erythematosus (see section "Special precautions").

Musculoskeletal and connective tissue disorders: arthralgia, myalgia, muscle weakness, fractures of the femur, wrist, or spine.

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

Reproductive system and breast disorders: gynaecomastia.

General disorders: discomfort, malaise, peripheral oedema, increased sweating.

Pediatric population.

The safety of omeprazole has been established in 310 children aged from 0 to 16 years. Limited data are available from long-term safety studies in 46 pediatric patients who received maintenance therapy with omeprazole for treatment of severe erosive esophagitis over 749 days. The adverse reaction profile is similar to that in adults during both short-term and long-term treatment. There are no long-term data on the effects of omeprazole treatment on sexual maturation and growth.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after a medicinal product is authorized is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua

Shelf life.

3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of the reach and sight of children.

Packaging.

10 capsules in a blister; 3 or 10 blisters in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Artura Pharmaceuticals Pvt. Ltd.

Manufacturer's address and location.

1505 Portia Road, Sri City SEZ, Setyavedu Mandal, Chittoor District – 517 588, Andhra Pradesh State, India.

Marketing Authorisation Holder.

Ananta Medikare Ltd.

Address of the Marketing Authorisation Holder.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.