Omeprazole-vista
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEPRAZOLE-VISTA (OMEPRAZOLE-VISTA)
Composition:
Active substance: omeprazole;
1 capsule contains omeprazole 20 mg or 40 mg in the form of gastro-resistant capsules;
Excipients: spherical sugar (corn starch, sucrose); hypromellose 2910 (E 464); talc (E 553b); titanium dioxide (E 171); sodium hydrogen phosphate, dihydrate (E 339 ii); methacrylic acid copolymer (type A) 30% dispersion (sodium lauryl sulfate, polysorbate 80, methacrylic acid copolymer); triethyl citrate (E 1505);
Capsule shell (body and cap): titanium dioxide (E 171), purified water, gelatin;
Ink composition (SW-9008): shellac, anhydrous alcohol, isopropyl alcohol, propylene glycol, butyl alcohol, concentrated ammonia solution, potassium hydroxide, purified water, black iron oxide (E 172).
Pharmaceutical form. Hard gastro-resistant capsules.
Main physicochemical properties:
20 mg capsules: white, opaque, hard gelatin capsules size №3, marked with 'OM' on the cap and '20' on the body, containing spherical pellets of white to beige color.
40 mg capsules: white, opaque, hard gelatin capsules size №1, marked with 'OM' on the cap and '40' on the body, containing spherical pellets of white to beige color.
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 proton pump inhibitor (PPI) of parietal cells. It acts rapidly and provides control by reversible inhibition of gastric acid secretion when administered once daily.
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 observed 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 20 mg to patients with duodenal ulcer results in a mean reduction in intragastric acidity of at least 80% over 24 hours, which is maintained thereafter, with a mean reduction in peak acid output following pentagastrin stimulation of approximately 70% 24 hours after drug administration.
Oral administration of omeprazole 20 mg to patients with duodenal ulcer maintains intragastric pH at ≥ 3 for an average of 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 given point in time.
No tachyphylaxis has been observed during omeprazole treatment.
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 high cure rates 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 increased frequency of occurrence of gastric foveolar hyperplasia has been reported. Such changes are a physiological consequence of marked inhibition of acid secretion, are benign, and appear to be reversible.
Reduction of gastric acidity by any medicinal product, including PPIs, increases the number of bacteria normally present in the gastrointestinal tract. Use of medicinal products 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 Clostridium difficile.
During treatment with antisecretory medicinal products, 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 long-term omeprazole treatment, an increase in the number of enterochromaffin-like (ECL) 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 an open-label study, children aged 0 to 24 months with a clinical diagnosis of gastroesophageal reflux disease (GERD) 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.
H. pylori eradication 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. H. pylori eradication rates were 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 volunteers 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 majority 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. Due to omeprazole's high affinity for CYP2C19, there is potential for competitive inhibition and metabolic interactions between medicinal products that are substrates for CYP2C19. However, due to its low affinity for CYP3A4, omeprazole is not capable of inhibiting the metabolism of other CYP3A4 substrates. In addition, omeprazole does not exert inhibitory effects on major CYP enzymes.
Approximately 3% of individuals of Caucasian ethnicity and 15–20% of individuals of Asian ethnicity 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 patients 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 plasma elimination half-life of omeprazole is typically less than 1 hour, both after single and repeated once-daily dosing. Omeprazole is completely eliminated from plasma during the dosing interval without a tendency for accumulation when administered once daily. 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-dependency 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 dysfunction, leading to increased AUC. Omeprazole did not show a tendency to accumulate when administered once daily.
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
Plasma concentrations observed in children aged 1 year and older treated with recommended doses are comparable to those in adult patients. In children under 6 months of age, omeprazole clearance is reduced due to low metabolic capacity.
Clinical characteristics
Indications
- Treatment of duodenal ulcers.
- Prevention of recurrence of duodenal 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 use of non-steroidal anti-inflammatory drugs (NSAIDs).
- 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 of the medicinal product.
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 is pH-dependent. Plasma concentrations of nelfinavir and atazanavir are reduced when these agents are used concomitantly with omeprazole.
Concomitant use of omeprazole and nelfinavir is contraindicated (see section "Contraindications").
Concomitant administration of omeprazole (40 mg once daily) reduced the mean exposure to nelfinavir by approximately 40%, and the mean exposure to its pharmacologically active metabolite M8 decreased 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 in healthy volunteers reduced atazanavir exposure by 75%. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. Concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg complex in healthy volunteers 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. In healthy volunteers, a pharmacokinetic (PK)/pharmacodynamic (PD) interaction was observed between clopidogrel (loading dose 300 mg / maintenance dose 75 mg daily) and omeprazole (80 mg daily orally), resulting in a mean reduction of 46% in exposure to clopidogrel's active metabolite 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 reduced, thus potentially reducing their 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 also metabolized by CYP2C19, their metabolism may be impaired and systemic exposure increased. Examples of such medicinal products include R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin. Plasma concentration monitoring of phenytoin is recommended during the first two weeks after initiation of omeprazole treatment, and after discontinuation of omeprazole therapy, monitoring and further dose adjustment may be necessary if the phenytoin dose has been modified.
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 concentration 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 concentration and renal function (creatinine clearance) is required when used concomitantly 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 lead to 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 or 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 (Hypericum perforatum)) 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 ruled out, as treatment with the medicinal product may mask its symptoms and delay correct diagnosis.
Concomitant use of atazanavir with PPIs is not recommended. If a combination of atazanavir with PPIs 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. PPI treatment 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 treatment, potential interactions with medicinal products 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 interfere with tests for detecting neuroendocrine tumors. To prevent this interference, omeprazole should be discontinued at least 5 days before measuring CgA levels. If CgA and gastrin levels have not returned to reference ranges after initial measurements, these parameters should be rechecked 14 days after discontinuation of PPI treatment. Acute tubulointerstitial nephritis (TIN) has been observed in patients treated with 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 absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be considered when treating patients with vitamin B12 deficiency or at risk of reduced vitamin B12 absorption during long-term therapy.
Use of PPIs, particularly at high doses and over prolonged periods (>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 that PPIs may increase the overall fracture risk by 10–40%. In some cases, this is associated with the presence of other risk factors in the patient. Patients at risk of osteoporosis should receive appropriate treatment and adequate intake of vitamin D and calcium.
In patients who have taken PPIs, including omeprazole, for at least 3 months, severe hypomagnesemia may occur (in most cases, patients had been taking the drug for 1 year). Hypomagnesemia may be suspected based on serious manifestations such as fatigue, muscle spasms, seizures, delirium, dizziness, and ventricular arrhythmias. However, it should be noted that in some cases, symptoms may be masked, delaying timely recognition of this complication. In most patients, symptoms of hypomagnesemia resolve and magnesium levels normalize after administration of magnesium supplements and discontinuation of PPIs.
In patients requiring long-term PPI treatment and concomitant use of digoxin or other medicinal products that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting treatment and periodically during treatment.
Very rare and rare cases of severe skin adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), which may be life-threatening or fatal, have been reported in association with omeprazole use.
PPI use has occasionally been associated with the development of subacute cutaneous lupus erythematosus (SCLE). If skin manifestations appear, especially in sun-exposed areas and accompanied by arthralgia, patients should seek immediate medical attention and discontinuation of omeprazole should be considered. A history of SCLE following PPI use may increase the risk of developing subacute SCLE when using other proton pump inhibitors.
In some cases, treatment of chronic conditions in children may require longer-term use of the medicinal product, although this is not recommended.
During long-term therapy, especially when treatment duration exceeds 1 year, patients should be under regular medical supervision.
Important information about excipients
This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially sodium-free.
This medicinal product contains sugar: 1 capsule of 20 mg contains 47 mg of sucrose, 1 capsule of 40 mg contains 94 mg of sucrose. Use with caution in patients with diabetes mellitus.
Use during pregnancy or breastfeeding
Pregnancy. Results from three prospective epidemiological studies (over 1000 pregnant women with successful outcomes) have not shown any negative effects of omeprazole on pregnancy or fetal/newborn health. The medicinal product may be used during pregnancy.
Breastfeeding. Omeprazole passes into breast milk, but its effect on the infant when used at therapeutic doses is unlikely.
Reproductive function. Oral administration of racemic omeprazole in animal studies did not affect reproductive function.
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. Adverse reactions such as dizziness and visual disturbances may occur. If such disorders occur, patients should not drive or operate machinery.
Method of Administration and Dosage
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, healing occurs within 2 weeks. For patients not fully healed after the initial course, healing typically occurs during an additional 2-week treatment period. For patients with a poor response to therapy, the recommended dose is 40 mg of omeprazole daily, and healing is usually achieved within 4 weeks.
Prevention of Recurrence of Duodenal Ulcers
For prevention of recurrence of duodenal ulcers in patients with a negative H. pylori test or when eradication of H. pylori is not feasible, 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.
Benign Gastric Ulcer Treatment
The recommended dose is 20 mg of omeprazole once daily. In most patients, gastric ulcer heals within 4 weeks. For patients not fully healed after the initial course, healing typically occurs during an additional 4-week treatment period. For patients with a poor response to therapy, the recommended dose is 40 mg of omeprazole daily, and healing is usually achieved within 8 weeks.
Prevention of Recurrence of Benign Gastric Ulcers
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.
For each regimen, if the patient remains H. pylori-positive, 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 not fully healed after the initial course, healing typically 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 Disease (GERD) Treatment
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 to continue treatment for an additional 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole daily is recommended, with recovery typically 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; 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 undergo further evaluation.
Zollinger–Ellison Syndrome Treatment
For patients with Zollinger–Ellison syndrome, dosage should be individually adjusted. Treatment continues until clinical manifestations disappear. 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 effective 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 Disease (GERD) Treatment
Symptomatic Treatment of Heartburn and Acid Regurgitation in GERD
Dosage 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 result 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 (with antibiotics) should be based on official national, regional, and local guidelines regarding bacterial resistance. The duration of treatment (from 7 to 14 days) and appropriate use of antibacterial medicinal products should also be considered.
Treatment must be conducted under medical supervision.
Dosage recommendations:
| Body weight |
Dosage |
| 15–30 kg |
Omeprazole 10 mg* + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. |
| 31–40 kg |
Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. |
| > 40 kg |
Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. |
* If a dose of 10 mg is required, the medicinal product should be administered in the appropriate dosage.
Special patient groups
Renal impairment. Dose adjustment is not required in 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 in elderly patients (see section "Pharmacokinetics").
Method of administration
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 a small amount of water. For patients with swallowing difficulties and for children who can drink or swallow semisolid food
The capsules may be opened and the contents swallowed directly with half a glass of water, or mixed with a slightly acidic liquid such as fruit juice, apple puree, or non-carbonated water. This mixture should be consumed immediately after preparation or within 30 minutes. The mixture should be stirred 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. Granules with enteric coating must not be chewed.
Children
The medicinal product may be used in 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 in children aged 4 years and older for the treatment (in combination with antibiotics) of duodenal ulcer caused by H. pylori, under medical supervision.
Overdose
Symptoms. 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.
Nausea, vomiting, dizziness, abdominal pain, headache, and diarrhea have been reported. Isolated cases of overdose were accompanied by apathy, depression, and confusion. However, all reported symptoms were transient, and no serious consequences were reported.
Treatment. Elimination rate does not change (first-order kinetics) with increasing dose. If necessary, treatment is symptomatic.
Adverse Reactions
The most common adverse reactions (in 1–10% of patients) are headache, abdominal pain, constipation, diarrhea, flatulence, and nausea/vomiting.
Serious skin adverse reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis, have been reported in association with omeprazole treatment.
The adverse reactions listed below have been reported during clinical trials with omeprazole or post-marketing use. None of these reactions have been established as dose-dependent.
All adverse reactions are listed by system organ class and frequency: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), and frequency not known (cannot be estimated from available data). The adverse reactions are classified into the following groups according to their effects on organs or organ systems.
Blood and lymphatic system disorders: rare – thrombocytopenia, leukopenia; very rare – agranulocytosis, pancytopenia.
Immune system disorders: rare – hypersensitivity reactions, including fever, angioedema, and anaphylactic reaction/shock.
Metabolism and nutrition disorders: rare – hyponatremia; frequency not known – hypomagnesemia; hypomagnesemia which may lead to hypokalemia; severe hypomagnesemia which may result in hypocalcemia.
Psychiatric disorders: uncommon – insomnia; rare – anxiety, confusion, depression; very rare – aggression, hallucinations.
Nervous system disorders: common – headache; uncommon – dizziness, paraesthesia, somnolence; rare – taste disturbance.
Eye disorders: rare – blurred vision.
Ear and labyrinth disorders: uncommon – vertigo.
Respiratory, thoracic and mediastinal disorders: rare – bronchospasm.
Gastrointestinal disorders: common – abdominal pain, diarrhea, constipation, nausea/vomiting, flatulence, fundic gland polyps (benign); rare – dry mouth, stomatitis, gastrointestinal candidiasis; frequency not known – microscopic colitis.
Hepatobiliary disorders: uncommon – increased liver enzymes; rare – hepatitis with or without jaundice; very rare – liver failure, encephalopathy in patients with pre-existing liver disease.
Skin and subcutaneous tissue disorders: uncommon – dermatitis, pruritus, rash, urticaria; rare – alopecia, photosensitivity, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS); very rare – erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis; frequency not known – subacute cutaneous lupus erythematosus.
Musculoskeletal and connective tissue disorders: uncommon – fracture of femur, wrist, or spine; rare – arthralgia, myalgia; very rare – muscle weakness.
Renal and urinary disorders: rare – tubulointerstitial nephritis (with possible progression to renal failure).
Reproductive system disorders: very rare – gynaecomastia.
General disorders: uncommon – malaise, peripheral edema; rare – increased sweating.
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 esophagitis over 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 study data on the effect of omeprazole treatment on sexual maturation and growth.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients or their legal representatives should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of the reach of children.
Packaging. 14 capsules in a blister; 2 blisters in a cardboard box.
Prescription status. Prescription only.
Manufacturer. Tova Pharmaceuticals Europe S.L.
Manufacturer's address and place of business.
Calle de Sant Martí 75-97, Polígon Industrial Martorelles, Martorelles, 08107, Spain.