Omez

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEZ® (OMEZ)

Composition:

Active substance: omeprazole;

1 capsule contains 20 mg of omeprazole;

Excipients: mannitol (E 421); lactose monohydrate; sodium lauryl sulfate; disodium hydrogen phosphate; sucrose; hypromellose; methacrylate copolymer (type C); sodium hydroxide; macrogol; talc; titanium dioxide (E 171);

Capsule shell composition: gelatin, methylparahydroxybenzoate (E 218), propylparahydroxybenzoate (E 216), carmoisine (E 122).

Medicinal form. Capsules.

Main physicochemical properties: hard transparent gelatin capsules, size 2, marked "OMEZ", with colorless body and pink cap. The capsule contents are white or almost 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 gastric proton pump in parietal cells. It acts rapidly and establishes control over 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 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 provides 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 the effect of omeprazole 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 administration of 20 mg omeprazole; mean reduction in peak acid output following pentagastrin stimulation is about 70% at 24 hours after omeprazole intake.

Oral administration of 20 mg omeprazole maintains intragastric pH ≥ 3 for a mean duration of 17 hours out of a 24-hour period in patients with duodenal ulcer. Due to reduced acid secretion and intragastric acidity, dose-dependently, omeprazole 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 actual plasma concentration at any given time.

No tachyphylaxis has been observed during omeprazole treatment.

Effect on Helicobacter pylori (H. pylori).

Peptic ulcer is associated with H. pylori, including duodenal ulcer and gastric ulcer. 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 development of peptic ulcer disease. H. pylori is the primary factor in the development 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 more rapid symptom relief, high healing rates of mucosal lesions, and long-term remission of peptic ulcer disease.

Other effects related to acid suppression.

During long-term treatment, a slightly increased incidence of glandular cysts in the stomach has been reported. These changes are a physiological consequence of sustained acid secretion suppression, are benign, and likely reversible.

Reduction of 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 slightly increases the risk of gastrointestinal infections, such as those caused by Salmonella, Campylobacter, and Clostridium difficile, particularly in hospitalized patients.

Use in pediatrics.

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 the condition in 90% of patients and significantly reduced reflux symptoms. In a blinded study without a comparator involving infants aged 0 to 24 months with a confirmed diagnosis of 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 eradication rate of H. pylori 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, no clinical benefit regarding dyspeptic symptoms was demonstrated. This study did not include children under 4 years of age.

Pharmacokinetics.

Absorption. Omeprazole is rapidly absorbed, with peak plasma levels reached approximately 1–2 hours after dosing. Absorption of omeprazole occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake has no effect on 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 individuals is approximately 0.3 L/kg body weight. Plasma protein binding of omeprazole is 97%.

Metabolism. Omeprazole is completely metabolized by the cytochrome P450 system. The majority of omeprazole metabolism depends on CYP2C19, 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 the high affinity of omeprazole for CYP2C19, there is potential for competitive inhibition and metabolic interactions with other drugs that are substrates of CYP2C19. However, due to 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 the Caucasian population and 15–20% of Asian populations 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 implications 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 during once-daily administration. Approximately 80% of an oral dose of omeprazole is excreted in urine as metabolites, and the remainder in feces, primarily via biliary secretion.

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

No metabolite has been found to have any effect on gastric acid secretion.

Special populations.

Hepatic impairment. In patients with impaired liver function, omeprazole metabolism is altered, leading to increased AUC. Omeprazole has not shown any tendency toward 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 in children aged 1 year and older, plasma concentrations are similar to those in adults. In children under 6 months of age, omeprazole clearance is low due to limited capacity to metabolize omeprazole.

Clinical characteristics.

Indications.

Adults:

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

Children:

children aged 1 year and older with body weight above 10 kg:

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

children aged 4 years and older:

• for the 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 "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 is pH-dependent

Suppression of gastric acid secretion during treatment with omeprazole and other PPIs may decrease or increase the absorption of medicinal products whose absorption depends on gastric pH. As with other agents that reduce gastric acidity, absorption of drugs such as ketoconazole, itraconazole, and erlotinib may be reduced, 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 administered concomitantly with omeprazole.

Concomitant use of omeprazole and nelfinavir is contraindicated. Concomitant administration of omeprazole (40 mg once daily) reduced the average exposure to nelfinavir by approximately 40%, and the average exposure to its pharmacologically active metabolite M8 was reduced by approximately 75–90%. The interaction may also be due to inhibition of CYP2C19 activity.

Concomitant use of omeprazole with atazanavir is not recommended. Concomitant administration of omeprazole (40 mg once daily) and 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. Concomitant 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 once daily.

Digoxin

Concomitant treatment with omeprazole (20 mg once daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10%. Cases of digoxin toxicity have been rarely 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 an average 16% reduction in maximum inhibition (ADP-induced) of platelet aggregation.

Conflicting data on the clinical consequences of PK/PD interaction with omeprazole regarding major cardiovascular events have been obtained from both 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 co-administered medicinal products metabolized by CYP2C19 may be reduced, and systemic exposure to these agents may be increased. 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/day, maintenance dose 75 mg/day) and omeprazole (80 mg orally once daily, i.e., a dose four times higher than the standard daily dose), resulting in an average 46% reduction in exposure to the active metabolite of clopidogrel and an average 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. If phenytoin dose adjustment has been made, monitoring and further dose adjustments should continue after discontinuation of omeprazole treatment.

Unknown interaction mechanism

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. Enhanced monitoring of tacrolimus concentrations 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, drugs that inhibit the activity of CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may cause increased omeprazole serum levels due to slowed metabolism. 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 drugs metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide.

Inducers of CYP2C19 and CYP3A4

Drugs that induce the activity of CYP2C19 or CYP3A4 (such as rifampicin and St. John's wort) may lead to decreased omeprazole serum 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; hematemesis or melena) and when gastric ulcer has been diagnosed or is suspected, malignancy should be ruled out, as treatment with the drug may mask its symptoms and delay correct diagnosis.

Concomitant use of atazanavir with proton pump inhibitors is not recommended. If co-administration of atazanavir with a proton pump inhibitor cannot be avoided, careful clinical monitoring (e.g., viral load) is recommended in combination 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 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 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, severe 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, tetany, seizures, delirium, vertigo, and ventricular arrhythmias. However, it should be noted that in some cases symptoms may be masked, which may delay timely recognition of this complication. In most patients, symptoms of hypomagnesemia resolve and levels normalize after administration of magnesium supplements and discontinuation of proton pump inhibitors.

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

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

Treatment with proton pump inhibitors slightly increases the risk of gastrointestinal infections caused by Salmonella, Campylobacter, and Clostridium difficile in hospitalized patients.

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 reduction of 46% in exposure to the active metabolite of clopidogrel and a mean reduction of 16% in maximum inhibitory effect (ADP-induced) on platelet aggregation.

The use of proton pump inhibitors, particularly at high doses and over prolonged periods, may be associated with a small increased risk of fractures, predominantly in elderly patients and those with additional risk factors. Although a causal relationship between omeprazole/esomeprazole use and osteoporotic fractures has not been established, patients at risk of progressive osteoporosis or osteoporotic fractures should be advised appropriate clinical monitoring according to current clinical guidelines.

Subacute cutaneous lupus erythematosus (SCLE)

The 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 discontinuing omeprazole. If SCLE occurs after prior treatment with a proton pump inhibitor, the risk of developing SCLE increases with subsequent use of other proton pump inhibitors.

Effect on diagnostic test results

During treatment with antisecretory drugs, serum gastrin levels may increase in response to reduced gastric acid secretion. Chromogranin A (CgA) levels may also rise due to decreased gastric acidity, which may interfere with diagnostic testing for neuroendocrine tumors.

Available published data indicate that PPIs should be discontinued 5–14 days before measuring CgA levels. This prevents misinterpretation of CgA levels following PPI use and allows values to return to baseline.

If chromogranin A and gastrin levels do not return to normal after initial testing, measurements should be repeated 14 days after stopping proton pump inhibitor therapy.

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

The drug should not be used in children for chronic conditions beyond the recommended duration.

Patients undergoing long-term treatment, especially longer than one year, should remain under medical supervision.

The medicinal product contains lactose and sucrose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take it. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

The medicinal product contains methylparahydroxybenzoate (E 218) and propylparahydroxybenzoate (E 216), which may cause allergic reactions (possibly delayed).

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

Omeprazole may cause serious skin reactions. Symptoms may include: skin redness, blisters, rash (see section "Adverse reactions").

If a patient experiences an allergic reaction, they should discontinue the drug and seek immediate medical attention.

Renal function impairment

Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking omeprazole. It may occur at any time during omeprazole therapy. Acute tubulointerstitial nephritis may progress to renal failure.

If ATIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.

Use during pregnancy or breastfeeding.

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

Omeprazole passes into breast milk, but when used at therapeutic doses, the likelihood of effects on the infant is low. If omeprazole use is necessary during breastfeeding, consult your doctor.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration.

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 recurrent cases, 40 mg of omeprazole once 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 when eradication of H. pylori is not possible, the recommended dose is 20 mg of omeprazole once daily. A daily dose of 10 mg may be sufficient for some patients. 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 to continue treatment for another 4 weeks. In severe or recurrent cases, 40 mg of omeprazole once daily is recommended, and healing is usually achieved within 8 weeks.

For prevention of recurrence in patients with gastric ulcer and insufficient 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 (NSAIDs), 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 to continue treatment for another 4 weeks.

For prevention of gastric and duodenal ulcers associated with use of nonsteroidal anti-inflammatory drugs (NSAIDs) 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 eradication of H. pylori, individual drug tolerance, local resistance patterns, and treatment guidelines should be taken into account.

• 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 (GERD), including reflux esophagitis.

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 to continue treatment for another 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole once daily is recommended, and healing is usually achieved within 8 weeks.

For long-term treatment of patients with gastroesophageal reflux disease, the recommended dose is 10 mg 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 may be sufficient for some patients; the dose should be adjusted individually. If the desired response 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 individually adjusted. Treatment continues until clinical symptoms resolve. The recommended initial dose is 60 mg of omeprazole once daily. Observations in over 90% of patients with severe disease and inadequate response to other treatments have shown efficacy of maintenance therapy with doses of 20–120 mg daily. Daily doses exceeding 80 mg should be divided and administered in two 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 (GERD).

Dosage recommendations:

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 is not achieved after 2–4 weeks, the patient should be further examined.

Children and adolescents aged 4 years and older.

Treatment of duodenal ulcer caused by H. pylori.

Combined therapy should be prescribed taking into account local patterns of bacterial resistance. Treatment duration (from 7 to 14 days) and appropriate use of antibacterial agents should also be considered. Treatment must be conducted under physician supervision.

Dosing recommendations:

* If a dose of 10 mg is required, administer the medicinal product in the appropriate dosage strength.

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 the capsules in the morning, preferably before a meal, without damaging the capsule (the capsules should not be chewed or crushed), and with half a glass of water.

For patients with swallowing difficulties and for children who can consume semi-solid food. The capsules may 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, applesauce, or still water. This mixture should be consumed immediately after preparation, within 30 minutes. Before administration, the mixture should be stirred and followed with half a glass of water. Do not use milk or carbonated water. The capsule contents (granules with enteric coating) must not be chewed.

Children.

The medicinal product may be administered to children aged 1 year and older with body weight above 10 kg, under medical supervision, for the indication of reflux esophagitis and symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease, and to children aged 4 years and older in combination with antibiotics for the treatment of duodenal ulcer associated with H. pylori infection, under medical supervision.

Overdose.

Data regarding the effects of omeprazole overdose in humans are limited. Cases of doses up to 560 mg of omeprazole have been reported in the scientific literature, and there have also been 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 were reversible. Elimination rate was not altered (first-order kinetics) with increasing dose. Treatment, if necessary, is symptomatic.

Adverse Reactions

The most commonly observed adverse effects are headache, abdominal pain, constipation, diarrhea, bloating, and nausea/vomiting. The following adverse reactions have been identified or suspected during clinical trials or post-marketing use of omeprazole.

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

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

Metabolism and nutrition disorders: hyponatremia, hypomagnesemia, severe hypomagnesemia which may lead to hypocalcemia. Hypomagnesemia may also be associated with hypokalemia.

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

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

Eye disorders: blurred vision.

Ear and labyrinth disorders: tinnitus, vertigo.

Respiratory, thoracic and mediastinal disorders: bronchospasm.

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

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

Skin and subcutaneous tissue disorders: dermatitis, pruritus, erythema, vesicles, rash, urticaria, alopecia, photosensitivity, polymorphic erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute cutaneous lupus erythematosus (see section "Special precautions").

Musculoskeletal and connective tissue disorders: arthralgia, myalgia, muscle weakness, fractures.

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

Reproductive system and breast disorders: gynecomastia.

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

Paediatric population.

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

Shelf life. 3 years.

Storage conditions. Store in the original packaging, protected from light, at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging.

10 capsules in a blister, 3 blisters per carton.

Prescription status. Prescription only.

Manufacturer.

Dr. Reddy’s Laboratories Ltd, FTO – II

Address of the manufacturer and location of its business operations.

Survey No. 42R, 43, 44R, 45R, 46R, 53, 54, 83, Bachupally, Bachupally Mandal, Medchal Malkajgiri District – 500090, Telangana State, India