Omeprazole -teva
Ukraine
Table of Contents
INSTRUCTION for medical use of the medicinal product Omeprazole-Teva
Composition:
Active substance: omeprazole;
1 capsule contains 20 mg or 40 mg of omeprazole in the form of gastro-resistant capsules;
Excipients: spherical sugar, povidone, sodium lauryl sulfate, sodium starch glycolate (type A), sodium phosphate, hypromellose, triethyl citrate, methacrylic acid copolymer (type A), sodium hydroxide, titanium dioxide (E 171), talc, erythrosine (E 127)*, indigo carmine (E 132)*, titanium dioxide (E 171)*, purified water*, gelatin*, quinoline yellow (E 104)*;
Ink composition: shellac, anhydrous ethanol, isopropyl alcohol, propylene glycol, butyl alcohol, povidone, sodium hydroxide, titanium dioxide (E 171).
*In the capsule shell composition
Pharmaceutical form. Hard gastro-resistant capsules.
Main physicochemical properties:
Omeprazole-Teva, 20 mg capsules: blue-orange capsules size №2, printed with “O” on the cap and “20” on the body, containing white to beige microgranules.
Omeprazole-Teva, 40 mg capsules: blue-orange capsules size №0, printed with “O” on the cap and “40” on the body, containing white to beige microgranules.
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 provides control by reversible inhibition of gastric acid secretion with once-daily dosing.
Omeprazole is a weak base that accumulates and is converted into its active form in the highly 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 step of acid production 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 reported pharmacodynamic effects are based on the effect of omeprazole on acid secretion.
Effect on gastric acid secretion
Oral administration of omeprazole once daily provides rapid and effective inhibition of gastric acid secretion both during the day and at night, with maximum effect achieved within 4 days of treatment.
Administration of omeprazole at a dose of 20 mg to patients with duodenal ulcer results in a mean reduction of intragastric acidity of at least 80% over 24 hours, which is maintained thereafter, with a mean reduction of peak acid output following pentagastrin stimulation of approximately 70% at 24 hours after drug administration.
Oral administration of omeprazole at a dose of 20 mg to patients with duodenal ulcer maintains intragastric pH at ≥ 3 on average for 17 out of 24 hours after drug administration.
Due to reduced acid secretion and intragastric acidity, omeprazole dose-dependently reduces/normalizes acid exposure in the esophagus in patients with gastroesophageal reflux disease (GERD). Inhibition of acid secretion is correlated with the area under the pharmacokinetic curve (AUC) of omeprazole, rather than with the actual plasma concentration at a specific point in time.
No cases of tachyphylaxis have been observed during treatment with omeprazole.
Effect on Helicobacter pylori (H. pylori)
H. pylori is associated with peptic ulcer, including gastric and duodenal ulcers. H. pylori is a major factor in the development of gastritis. H. pylori, together with gastric acid, is a primary factor in the development of peptic ulcer disease. H. pylori is the main factor in the development of atrophic gastritis, associated with an increased risk of gastric cancer.
Eradication of H. pylori using omeprazole and antibiotics is associated with a high cure rate and long-term remission of peptic ulcers.
Various dual therapy regimens have been analyzed and found to be less effective than triple therapy. However, their use may be considered in cases where known high susceptibility excludes the use of any triple combination.
Other effects related to acid suppression
During long-term treatment, a slightly higher frequency of occurrence of gastric fundic gland polyps has been reported. Such changes are a physiological consequence of profound acid secretion inhibition, are benign, and appear to be reversible.
Reduction of gastric acidity by any means, including PPIs, increases the number of bacteria normally present in the gastrointestinal tract. Treatment with agents that reduce gastric acidity may lead to a slight increase in the risk of gastrointestinal infections, particularly those caused by Salmonella, Campylobacter, and in hospitalized patients possibly also Clostridium difficile.
During treatment with antisecretory drugs, serum gastrin levels increase in response to reduced acid secretion. Due to reduced gastric acidity, chromogranin A (CgA) levels rise. Elevated CgA levels may interfere with the diagnosis of neuroendocrine tumors. Available published data indicate that PPI treatment should be discontinued for a period of 5 days to 2 weeks before measuring CgA levels. This allows CgA levels, which may be falsely elevated after PPI treatment, to return to the reference range.
During prolonged treatment with omeprazole, an increase in the number of enterochromaffin-like cells has been observed in some patients (both children and adults), possibly related to increased serum gastrin levels. The clinical significance of these findings is not established.
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 simple blind study, children aged 0 to 24 months with a clinically established diagnosis of gastroesophageal reflux disease received omeprazole treatment at doses of 0.5, 1.0, or 1.5 mg/kg body weight. The frequency of vomiting/regurgitation episodes decreased by 50% after 8 weeks of treatment, regardless of dose.
Eradication of H. pylori in children
A randomized, double-blind clinical trial (the Héliot study) 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) with omeprazole + amoxicillin + clarithromycin compared to 9.4% (3/32 patients) with amoxicillin + clarithromycin. However, no clinical advantages regarding dyspeptic symptoms were demonstrated. This study provides no information for children under 4 years of age.
Pharmacokinetics.
Absorption
Omeprazole and omeprazole magnesium salt are acid-labile and therefore administered orally as enteric-coated granules in capsules or tablets. Omeprazole absorption is rapid, with peak plasma levels reached approximately 1–2 hours after dose administration. Absorption of omeprazole occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake does not affect bioavailability. Systemic availability (bioavailability) of a single dose of omeprazole is approximately 40%. After repeated once-daily dosing, bioavailability increases to approximately 60%.
Distribution
The apparent volume of distribution in healthy subjects is approximately 0.3 L/kg body weight. Omeprazole is 97% bound to plasma proteins.
Metabolism
Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The major part of its metabolism depends on the specific isoenzyme CYP2C19, responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. Another part depends on another specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. As a result of omeprazole's high affinity for CYP2C19, there is potential for competitive inhibition and metabolic interactions between drugs that are substrates for CYP2C19. However, due to low affinity for CYP3A4, omeprazole is not capable of inhibiting the metabolism of other CYP3A4 substrates. Additionally, omeprazole does not have inhibitory effects on major CYP enzymes.
Approximately 3% of Caucasian individuals and 15–20% of Asian individuals have a deficiency of functional CYP2C19 enzyme and are therefore referred to as "poor metabolizers." In these individuals, omeprazole metabolism is likely primarily catalyzed by CYP3A4. After repeated administration of 20 mg omeprazole once daily, the AUC in "poor metabolizers" was 5–10 times higher than in subjects with functional CYP2C19 enzyme ("extensive metabolizers"). Mean peak plasma concentrations were also 3–5 times higher. These data do not affect omeprazole dosing.
Elimination
The elimination half-life of omeprazole in plasma is generally less than 1 hour, both after single and repeated once-daily dosing. Omeprazole is completely cleared from plasma between doses without a tendency for accumulation during once-daily administration. Nearly 80% of an oral dose of omeprazole is excreted in urine as metabolites, the remainder in feces, primarily via biliary secretion.
The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear dose-AUC relationship after repeated dosing. This time- and dose-dependence is due to reduced first-pass metabolism and systemic clearance, likely caused by inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g., sulfone). No metabolite of omeprazole has been shown to affect gastric acid secretion.
Special patient groups
Hepatic impairment
Omeprazole metabolism is impaired in patients with hepatic impairment, leading to increased AUC. Omeprazole did not show a tendency to accumulate with once-daily administration.
Renal impairment
The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are not altered in patients with renal impairment.
Elderly patients
The rate of omeprazole metabolism is slightly reduced in elderly patients (75–79 years).
Children
During treatment of children aged 1 year and older using recommended doses, plasma concentrations comparable to those in adult patients were observed. In children under 6 months of age, omeprazole clearance is reduced due to low metabolic capacity for omeprazole.
Clinical characteristics.
Indications.
Use in adults
- Treatment of duodenal ulcers
- Prevention of recurrence of duodenic ulcers
- Treatment of benign gastric ulcers
- Prevention of recurrence of benign gastric ulcers
- Eradication of H. pylori in combination with appropriate antibiotics in peptic ulcer disease
- Treatment of gastric and duodenal ulcers associated with NSAID use
- Prevention of gastric and duodenal ulcers associated with NSAID use in patients at risk
- Treatment of reflux esophagitis
- Long-term maintenance therapy in patients with gastroesophageal reflux disease (GERD)
- Treatment of symptoms of gastroesophageal reflux disease
- Treatment of Zollinger–Ellison syndrome.
Use in 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
Children aged 4 years and older
- In combination with antibiotics for treatment of duodenal ulcer caused by H. pylori.
Contraindications.
Hypersensitivity to omeprazole, substituted benzimidazoles, or to any of the excipients. Omeprazole, like other proton pump inhibitors, 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
Suppression of gastric acidity during omeprazole treatment may decrease or increase absorption of medicinal products whose absorption depends on gastric pH.
Plasma concentrations of nelfinavir and atazanavir are reduced when these medicinal products are used concomitantly with omeprazole.
Concomitant use of omeprazole and nelfinavir is contraindicated (see section "Contraindications").
Concomitant administration of omeprazole (40 mg once daily) reduces mean nelfinavir exposure by approximately 40%, and mean exposure to its pharmacologically active metabolite M8 is reduced by approximately 75–90%. The interaction may also involve inhibition of CYP2C19.
Concomitant use of omeprazole and atazanavir is not recommended. Concomitant administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg complex reduced atazanavir exposure by 75% in healthy volunteers. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. In healthy volunteers, concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg complex reduced atazanavir exposure by 30% compared to administration of atazanavir 300 mg/ritonavir 100 mg complex.
Concomitant administration of omeprazole (20 mg once daily) and digoxin in healthy volunteers increased digoxin bioavailability by 10%. Rare cases of digoxin toxicity have been reported. Concomitant use of digoxin and high doses of omeprazole should be approached with caution in elderly patients. In such cases, intensified therapeutic monitoring of digoxin by the physician is indicated.
Pharmacokinetic (PK)/pharmacodynamic (PD) interaction between clopidogrel (loading dose 300 mg/maintenance dose 75 mg daily) and omeprazole (80 mg daily orally) was observed in healthy volunteers, 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. Conflicting data on the clinical significance of this PK/PD interaction regarding major cardiovascular events have been obtained from observational and clinical studies. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.
Other active substances
Absorption of posaconazole, erlotinib, ketoconazole, and itraconazole is significantly decreased, thereby potentially reducing clinical efficacy. Concomitant use of the medicinal product with posaconazole and erlotinib should be avoided.
Active substances metabolized by CYP2C19
Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme involved in omeprazole metabolism. Therefore, when used concomitantly with active substances that are also metabolized by CYP2C19, their metabolism may be impaired and systemic exposure increased. Examples include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin.
Plasma concentrations of phenytoin should be monitored during the first two weeks after initiation of omeprazole treatment. If the phenytoin dose is adjusted, monitoring and further dose adjustments are required after discontinuation of omeprazole.
In healthy volunteers, administration of omeprazole 40 mg increased Cmax and AUC of cilostazol by 18% and 26%, respectively, and of one of its active metabolites by 29% and 69%, respectively.
Unknown interaction mechanisms
Concomitant administration of omeprazole with saquinavir/ritonavir increased saquinavir plasma concentrations by approximately 70%, which was associated with good tolerability in HIV-infected patients.
Increased serum concentrations of tacrolimus have been reported with concomitant use of omeprazole. Intensified monitoring of tacrolimus concentrations and renal function (creatinine clearance) is required during concomitant administration with omeprazole, and dose adjustment of tacrolimus may be necessary.
Increased levels of methotrexate have been reported in some patients when used concomitantly with PPIs. In cases where high-dose methotrexate 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 metabolism involves CYP2C19 and CYP3A4, active substances known to inhibit CYP2C19 or CYP3A4 (e.g., clarithromycin and voriconazole) may increase omeprazole serum levels by reducing its metabolic rate. Concomitant treatment with omeprazole and voriconazole may result in more than a two-fold 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 when long-term treatment is indicated.
Inducers of CYP2C19 and/or CYP3A4
Active substances known to induce CYP2C19, CYP3A4, or both enzymes (e.g., rifampicin, St. John’s wort) may lead to decreased omeprazole serum levels by accelerating its metabolism.
Special precautions for use.
If alarming symptoms such as significant unintentional weight loss, persistent vomiting, dysphagia, hematemesis, or melena are present, or if there is suspicion or evidence of ulceration, malignancy must be excluded, as drug administration may mask its symptoms and delay correct diagnosis.
Concomitant use of atazanavir with PPIs is not recommended. If a combination of atazanavir with a PPI cannot be avoided, careful clinical monitoring (e.g., viral load) is recommended, along with increasing the atazanavir dose to 400 mg with 100 mg ritonavir; the omeprazole dose should not exceed 20 mg.
Treatment with proton pump inhibitors may lead to a slight increase in the risk of intestinal infections caused by bacteria such as Salmonella and Campylobacter, and possibly Clostridium difficile in hospitalized patients.
Omeprazole is an inhibitor of CYP2C19. At the beginning or end of omeprazole therapy, potential interactions with drugs metabolized by CYP2C19, such as clopidogrel, should be considered. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.
Increased chromogranin A (CgA) levels may affect test results for detecting neuroendocrine tumors. To prevent such interference, omeprazole should be discontinued at least 5 days before measuring CgA levels. If CgA and gastrin levels do not return to reference ranges after initial measurements, testing should be repeated 14 days after discontinuation of proton pump inhibitor therapy.
Acute tubulointerstitial nephritis (TIN) has been observed in patients receiving omeprazole. It may occur at any time during omeprazole therapy. Acute tubulointerstitial nephritis may progress to renal failure. If TIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.
Omeprazole, like other acid-inhibiting agents, may reduce vitamin B12 (cyanocobalamin) absorption due to hypo- or achlorhydria. This should be considered when treating patients with vitamin B12 deficiency or those at risk of reduced vitamin B12 absorption during long-term therapy.
Use of proton pump inhibitors, particularly at high doses and for prolonged durations (>1 year), may slightly increase the risk of fractures of the hip, wrist, and spine, primarily in elderly patients or those with other risk factors. Observational studies suggest PPIs may increase fracture risk by 10–40%. In some cases, this is associated with other patient-specific risk factors. Patients at risk of osteoporosis should receive appropriate treatment and adequate intake of vitamin D and calcium.
In patients receiving PPIs, including omeprazole, for at least 3 months (in most cases, after 1 year of treatment), severe hypomagnesemia may occur. Hypomagnesemia may present with serious symptoms such as fatigue, muscle spasms, seizures, delirium, dizziness, and ventricular arrhythmias. However, symptoms may be masked in some cases, delaying timely recognition of this complication. In most patients, symptoms resolve and magnesium levels normalize after magnesium supplementation and discontinuation of proton pump inhibitors.
In patients requiring long-term PPI therapy and concomitant use of digoxin or other drugs that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting treatment and periodically during therapy.
Serious skin adverse reactions, including Stevens–Johnson syndrome (SJS), 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, have been reported very rarely and, accordingly, rarely in association with omeprazole use.
PPI use has occasionally been associated with subacute cutaneous lupus erythematosus (SCLE). If skin manifestations appear, especially in sun-exposed areas and accompanied by arthralgia, patients should seek immediate medical advice and discontinuation of omeprazole should be considered. A history of SCLE following PPI use may increase the risk of developing subacute SCLE with other proton pump inhibitors.
In some cases, treatment of chronic conditions in children may require longer-term use of the drug, although this is not recommended.
During long-term therapy, and particularly when treatment duration exceeds 1 year, patients should be under regular medical supervision.
If a patient has known intolerance to certain sugars, consultation with a physician is advised before taking this medicinal product.
Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this product.
This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially sodium-free.
Use during pregnancy or breastfeeding.
Pregnancy. Results from three prospective epidemiological studies (more than 1000 pregnant women with successful deliveries) showed no adverse effects of omeprazole on pregnancy outcomes or on fetal/neonatal health. The drug may be used during pregnancy.
Breastfeeding. Omeprazole passes into breast milk, but its effects on the infant when used at therapeutic doses are unlikely.
Reproductive function. Oral administration of racemic omeprazole in animal studies did not affect reproductive function.
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. If such disorders occur, patients should not drive or operate machinery.
Dosage and Administration
Before initiating treatment, the presence of a malignant condition must be excluded, as omeprazole therapy may mask symptoms and complicate diagnosis.
Dosage for adults
Duodenal ulcer treatment
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 have not fully healed after the initial treatment course, healing usually occurs during an additional 2-week treatment period. In patients with poor response to therapy, the recommended dose is 40 mg of omeprazole daily, and ulcer healing is typically achieved within 4 weeks.
Prevention of duodenal ulcer recurrence
For prevention of duodenal ulcer recurrence 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 treatment is ineffective, the dose may be increased to 40 mg.
Gastric ulcer treatment
The recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. For patients who have not fully healed after the initial course, healing usually occurs during an additional 4-week treatment period. In patients with poor response to therapy, the recommended dose is 40 mg of omeprazole daily, and healing is typically achieved within 8 weeks.
Prevention of benign gastric ulcer recurrence
The recommended dose for prevention of recurrence in patients with poor response of gastric ulcer to therapy is 20 mg of omeprazole once daily. If necessary, the dose may be increased to 40 mg once daily.
H. pylori eradication 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 and recommendations 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.
If the patient remains H. pylori-positive after any regimen, therapy may be repeated.
Treatment of NSAID-associated gastric and duodenal ulcers
For treatment of gastric and duodenal ulcers associated with NSAID use, the recommended dose is 20 mg of omeprazole once daily. In most patients, ulcer healing occurs within 4 weeks. For patients who have not fully healed after the initial course, healing usually occurs during an additional 4-week treatment period.
Prevention of NSAID-associated gastric and duodenal ulcers in high-risk patients
For prevention of gastric and duodenal ulcers associated with NSAID use in patients at high risk (age over 60 years, history of gastric or duodenal ulcer, history of upper gastrointestinal bleeding), the recommended dose is 20 mg of omeprazole once daily.
Gastroesophageal reflux esophagitis treatment
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 should continue treatment for an additional 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with healing usually achieved within 8 weeks.
Long-term maintenance therapy in patients with GERD
For long-term treatment of patients with gastroesophageal reflux disease (GERD), 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.
Treatment of GERD symptoms
For treatment of GERD symptoms, 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 effect is not achieved after 4 weeks of treatment with 20 mg of omeprazole daily, the patient should undergo further examination.
Zollinger–Ellison syndrome treatment
Dosage for patients with Zollinger–Ellison syndrome 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 at 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
Gastroesophageal reflux esophagitis treatment
Symptomatic treatment of heartburn and acid regurgitation in GERD
Dosing recommendations:
| Age |
Body weight |
Dosage |
| ≥ 1 year |
10–20 kg |
10 mg* once daily. |
| ≥ 2 years |
> 20 kg |
20 mg once daily. |
Treatment of reflux esophagitis: treatment duration is 4–8 weeks.
Symptomatic treatment of heartburn and acid regurgitation in GERD: treatment duration is 2–4 weeks. If the desired effect is not 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 the appropriate use of antibacterial agents should also be considered. Treatment should be conducted under physician supervision.
Dosing recommendations:
| Body weight |
Dosage |
| 15–30 kg |
Omeprazole 10 mg* + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. Take the medications together twice daily for 1 week. |
| 31–40 kg |
Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. Take the medications together twice daily for 1 week. |
| > 40 kg |
Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. Take the medications together twice daily for 1 week. |
* – if a dose of 10 mg is required, the medicinal product should be administered in the appropriate dosage form.
Special patient groups
Renal impairment. Dose adjustment is not required for patients with renal impairment (see section "Pharmacokinetics").
Hepatic impairment. A daily dose of 10–20 mg is sufficient for patients with hepatic impairment (see section "Pharmacokinetics").
Elderly patients. Dose adjustment is not required for elderly patients (see section "Pharmacokinetics").
Method of administration
It is recommended to take the capsules in the morning, preferably before meals, without damaging the capsule (the capsules must not be chewed or crushed), with a small amount of water.
For patients with swallowing difficulties and for children who can drink or swallow semi-solid food. The capsules may be opened and the contents swallowed directly, followed by half a glass of water, or mixed with a slightly acidic drink such as fruit juice, apple puree, or still water. This mixture must be consumed immediately after preparation or within 30 minutes. The mixture should be shaken before administration and followed by half a glass of water.
Alternatively, patients may suck the capsule and swallow the granules, followed by half a glass of water. The 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 treatment of reflux esophagitis, symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease, and to children aged 4 years and older for the treatment of duodenal ulcer associated with H. pylori, under medical supervision.
Overdose.
Very limited data are available on the effects of omeprazole overdose in humans. Literature reports doses up to 560 mg of omeprazole, and there are also data on single oral doses reaching up to 2400 mg of omeprazole, i.e., 120 times higher than the usual recommended dose.
Symptoms reported include nausea, vomiting, dizziness, abdominal pain, headache, and diarrhea. Isolated cases of overdose were accompanied by apathy, depression, and confusion. However, all reported symptoms were transient, and no serious consequences have been reported.
Elimination rate (first-order kinetics) does not change with increasing dose. If necessary, treatment is symptomatic.
Side effects
The most common adverse reactions (in 1–10% of patients) are headache, abdominal pain, constipation, diarrhoea, flatulence, and nausea/vomiting.
Serious skin adverse reactions, including Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported in association with omeprazole treatment.
The following adverse reactions have been reported during clinical trials with omeprazole or post-marketing use. None of these reactions were considered dose-dependent.
Adverse reactions are classified into the following organ system groups.
Blood and lymphatic system disorders: thrombocytopenia, leukopenia, agranulocytosis, pancytopenia.
Immune system disorders: hypersensitivity reactions, including fever, angioedema, and anaphylactic reaction/shock.
Metabolism and nutrition disorders: hyponatremia, hypomagnesemia, hypomagnesemia which may lead to hypokalemia; severe hypomagnesemia which may result in hypocalcemia.
Psychiatric disorders: insomnia, anxiety, confusion, depression, aggression, hallucinations.
Nervous system disorders: headache, dizziness, paraesthesia, somnolence, taste disturbance.
Eye disorders: blurred vision.
Ear and labyrinth disorders: vertigo.
Respiratory, thoracic and mediastinal disorders: bronchospasm.
Gastrointestinal disorders: diarrhoea, constipation, abdominal pain, nausea/vomiting, flatulence, fundic gland polyps (benign), 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, rash, urticaria, alopecia, photosensitivity, acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, Stevens–Johnson syndrome, toxic epidermal necrolysis (TEN), subacute cutaneous lupus erythematosus.
Musculoskeletal and connective tissue disorders: fracture of the femur, wrist, or spine, arthralgia, myalgia, muscle weakness.
Renal and urinary disorders: tubulointerstitial nephritis (with possible progression to renal failure).
Reproductive system disorders: gynaecomastia.
General disorders: malaise, peripheral oedema, increased sweating, pyrexia.
Children
The safety of omeprazole has been evaluated in 310 children aged 0 to 16 years with acid-related disorders. Limited data are available from long-term safety studies in 46 children who received maintenance therapy with omeprazole for the treatment of severe erosive oesophagitis 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 long-term data on the effects of omeprazole treatment on sexual maturation and growth.
Reporting of suspected adverse reactions. All suspected adverse reactions and lack of efficacy should be reported via the following link: https://aisf.dec.gov.ua/
Shelf life. 2 years.
Storage conditions. Store at temperatures not exceeding 30 °C. Keep out of reach of children.
Packaging. 10 capsules in a blister; 3 blisters per carton.
Prescription status. Prescription only.
Manufacturer. Teva Pharma S.L.U.
Manufacturer's address and place of business.
Polígono Industrial Malpica c/C nº 4, 50016, Zaragoza, Spain