Omeprazole 20 ananta
Ukraine
Table of Contents
INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT OMEPRAZOLE 20 ANANTA (OMEPRAZOLE 20 ANANTA)
Composition:
Active substance: omeprazole;
1 capsule* contains omeprazole (in the form of enteric-coated pellets) 20 mg;
Excipients: maize starch, sucrose, spherical sugar, light magnesium carbonate, talc, sodium phosphate, hydroxypropylcellulose, hypromellose (hydroxypropylmethylcellulose), methacrylate copolymer (type A), polyethylene glycol (macrogol) 6000, colloidal anhydrous silicon dioxide, sodium hydroxide, titanium dioxide (E 171).
*Capsule shell contains:
Body: titanium dioxide (E 171), gelatin, carmoisine (E 122), tartrazine (E 102), brilliant blue (E 133);
Cap: titanium dioxide (E 171), gelatin, erythrosine (E 127).
Pharmaceutical form. Capsules.
Main physicochemical properties: hard gelatin capsules with grey body and pink cap; capsule contents – white or almost white pellets (granules).
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 is a racemic mixture of two enantiomers that reduces gastric acid secretion through a targeted mechanism of action. It is a specific inhibitor of the proton pump (PPI) in the parietal cells of the stomach. It acts rapidly and causes controlled, reversible inhibition of gastric acid secretion when administered once daily.
Omeprazole is a weak base that accumulates and is converted into its active form in the acidic environment of the intracellular canaliculi of parietal cells, where it inhibits the H+/K+-ATPase enzyme—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 omeprazole once daily results in rapid and effective inhibition of daytime and nighttime gastric acid secretion. The maximum effect is achieved within 4 days of treatment. In patients with duodenal ulcer, omeprazole at a dose of 20 mg reduces gastric acidity by approximately 80% on average over 24 hours after administration, and the average 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 an average of 17 hours out of a 24-hour period in patients with duodenal ulcer.
Due to reduced acid secretion and intragastric acidity, omeprazole reduces/normalizes acid exposure in the esophagus in patients with gastroesophageal reflux disease (GERD), depending on the dose.
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 disease, including duodenal ulcer and gastric ulcer, is associated with H. pylori. H. pylori is considered a major factor in the development of gastritis, and together with gastric acid, it plays a decisive role in the development of peptic ulcer disease. H. pylori is also a key 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 high healing rates and prolonged remission of peptic ulcers.
Dual therapy has been tested and found to be less effective than triple therapy. However, it may be considered in cases where known hypersensitivity excludes the use of any triple combination.
Other Effects Related to Acid Suppression
During long-term treatment, a slightly increased frequency of glandular cysts in the stomach has been reported. These changes are a physiological consequence of acid secretion inhibition, the cysts are benign and reversible.
Reduced gastric acidity, caused by any agent including PPIs, 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 and Campylobacter, and in hospitalized patients, possibly also those caused by Clostridium difficile.
During treatment with antisecretory drugs, plasma gastrin concentration increases as a result of reduced hydrochloric acid secretion. Due to reduced hydrochloric acid secretion, chromogranin A (CgA) levels increase. Elevated CgA levels may affect test results for detecting neuroendocrine tumors. Based on available published data, it is recommended that PPI therapy be discontinued 5 to 14 days before planned CgA measurements to avoid false-positive results caused by PPI use.
During long-term omeprazole therapy, an increase in the number of enterochromaffin-like cells (ECL) has been observed in some patients (both children and adults), possibly due to elevated serum gastrin levels. These findings are considered to be of no clinical significance.
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 another study, infants aged 0 to 24 months with a clinically confirmed diagnosis of gastroesophageal reflux disease received omeprazole 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
According to data from a randomized, double-blind clinical trial, omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) was safe and effective in treating H. pylori infection in children aged 4 years and older with gastritis. The H. pylori eradication rate was 74.2% (23/31 patients) with omeprazole + amoxicillin + clarithromycin, compared to 9.4% (3/32 patients) with amoxicillin + clarithromycin alone. However, no clinical benefit regarding dyspeptic symptoms was demonstrated. Data in children under 4 years of age are lacking.
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 dosing. Absorption occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake does not affect bioavailability. Systemic availability (bioavailability) of a single dose of omeprazole is approximately 40%. After repeated once-daily dosing, bioavailability increases to about 60%.
Distribution
The apparent volume of distribution in healthy volunteers is approximately 0.3 L/kg body weight. Omeprazole is 97% bound to plasma proteins.
Biotransformation
Omeprazole is completely metabolized by the cytochrome P450 (CYP) system. The majority of its metabolism depends on the polymorphically expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the main metabolite in plasma. Another part depends on a different specific isoenzyme, CYP3A4, responsible for the formation of omeprazole sulfone. Due to omeprazole's high affinity for CYP2C19, competitive inhibition and metabolic interactions may occur between omeprazole and other drugs that are substrates of CYP2C19. However, due to its low affinity for CYP3A4, omeprazole does not inhibit the metabolism of other CYP3A4 substrates. Additionally, omeprazole does not inhibit major CYP enzymes.
Approximately 3% of Caucasian and 15–20% of Asian individuals have a deficiency in 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 usually less than 1 hour, both after single and repeated once-daily dosing. Omeprazole is completely cleared from plasma between doses, with no tendency for accumulation when administered once daily. Approximately 80% of an oral dose of omeprazole is excreted in urine as metabolites, the remainder in feces via biliary secretion.
Linearity/Non-linearity
The AUC of omeprazole increases with repeated administration. This increase is dose-dependent and results in a non-linear relationship between AUC and dose after repeated dosing. This time- and dose-dependent relationship 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 effect of omeprazole metabolites on gastric acid secretion has been observed.
Special Patient Groups
Hepatic Impairment
Omeprazole metabolism is impaired in patients with hepatic dysfunction, leading to increased AUC. Omeprazole does 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 of age).
Children
Plasma concentrations observed during treatment of children aged 1 year and older using recommended doses were similar to those in adult patients. In children under 6 months of age, omeprazole clearance is reduced due to low metabolic capacity.
Clinical characteristics.
Indications.
Adults
- Treatment of duodenal ulcer;
- prevention of recurrence of duodenal ulcer;
- treatment of gastric ulcers;
- prevention of recurrence of gastric ulcers;
- in combination with appropriate antibiotics for eradication of Helicobacter pylori (H. pylori) in peptic ulcer disease;
- treatment of NSAID-associated gastric and duodenal ulcers;
- prevention of NSAID-associated gastric and duodenal ulcers in patients at risk;
- treatment of reflux esophagitis;
- long-term treatment of patients with healed reflux esophagitis;
- treatment of symptoms of gastroesophageal reflux disease (GERD);
- treatment of Zollinger–Ellison syndrome.
Children
Children aged 1 year and older with body weight ≥ 10 kg
- Treatment of reflux esophagitis;
- symptomatic treatment of heartburn and acid regurgitation in GERD.
Children aged 4 years and adolescents
- 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 (PPIs), should not be used concomitantly with nelfinavir (see section "Interaction with other medicinal products and other types of interactions").
Interaction with other medicinal products and other types of interactions.
Effect of omeprazole on the pharmacokinetics of other medicinal products
Medicinal products whose absorption is pH-dependent
Reduced gastric acidity during omeprazole treatment may increase or decrease absorption of drugs whose absorption depends on gastric pH.
Nelfinavir and atazanavir
Plasma concentrations of nelfinavir and atazanavir are reduced when these drugs are administered concomitantly with omeprazole.
Concomitant administration of omeprazole and nelfinavir is contraindicated (see section "Contraindications").
Concomitant use 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 (see section "Special precautions for use"). Concomitant administration of omeprazole (40 mg once daily) with atazanavir 300 mg/ritonavir 100 mg combination 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. Concomitant administration of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg combination reduced atazanavir exposure by 30% compared to atazanavir 300 mg/ritonavir 100 mg combination.
Digoxin
Concomitant treatment with omeprazole (20 mg daily) and digoxin increases 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. Therapeutic drug monitoring of digoxin should be intensified.
Clopidogrel
A pharmacokinetic/pharmacodynamic (PK/PD) interaction between clopidogrel (loading dose 300 mg followed by 75 mg daily) and omeprazole (80 mg daily) was observed in a clinical study involving healthy volunteers, resulting in a 46% reduction in exposure to the active metabolite of clopidogrel and a mean 16% reduction in maximum inhibition (adenosine diphosphate (ADP)-induced) of platelet aggregation.
Conflicting data on the clinical implications of this PK/PD interaction regarding major cardiovascular events have been reported in observational and clinical studies. Therefore, concomitant use of omeprazole and clopidogrel should be avoided (see section "Special precautions for use").
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 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.
Cilostazol
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.
Phenytoin
Monitoring of phenytoin plasma concentrations is recommended during the first two weeks after initiation of omeprazole treatment and whenever phenytoin dose adjustment is made. Monitoring and further dose adjustment should continue after discontinuation of omeprazole.
Interactions with unknown mechanisms
Saquinavir
Concomitant administration of omeprazole with saquinavir/ritonavir increased saquinavir plasma concentrations by approximately 70%, which was associated with good tolerability in HIV-infected patients.
Tacrolimus
Increased serum concentrations of tacrolimus have been reported with concomitant use of omeprazole. Serum tacrolimus concentrations and renal function (creatinine clearance) should be closely monitored during concomitant use with omeprazole, and tacrolimus dosage adjusted as necessary.
Metotrexate
Data indicate increased methotrexate levels in some patients when administered 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 is metabolized by CYP2C19 and CYP3A4, drugs that inhibit CYP2C19, CYP3A4, or both enzymes (such as clarithromycin and voriconazole) may increase omeprazole serum levels by slowing its metabolism. Concomitant use of voriconazole may lead to more than a two-fold increase in omeprazole exposure. As high doses of omeprazole are well tolerated, dose adjustment is not required during short-term concomitant use. 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
Drugs that induce CYP2C19 and/or CYP3A4 or both enzymes (such as rifampicin, St. John's wort) may lead to decreased omeprazole serum levels by accelerating its metabolism.
Special precautions for use.
In the presence of any alarming symptom (e.g., significant weight loss, recurrent vomiting, dysphagia, hematemesis, or melena) or suspicion or presence of gastric ulcer, malignancy must be excluded, as the drug may mask its symptoms and delay correct diagnosis.
Concomitant use of atazanavir with PPIs is not recommended (see section "Interaction with other medicinal products and other forms of interaction"). 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.
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 therapy, potential interactions with medicinal products metabolized by CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole (see section "Interaction with other medicinal products and other forms of interaction"). The clinical significance of this interaction is not fully established. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.
In patients taking PPIs, including omeprazole, for at least 3 months, significant hypomagnesemia may occur (in most cases, patients had been taking the drug for approximately 1 year). Hypomagnesemia may be suspected based on serious manifestations such as fatigue, muscle spasms, seizures, delirium, vertigo, and ventricular arrhythmias. However, it should be noted that in some cases symptoms may be masked, hindering timely recognition of this complication. In most patients, symptoms of hypomagnesemia resolve and magnesium levels normalize after administration of magnesium supplements and discontinuation of the PPI.
In patients requiring long-term PPI therapy, and in patients concomitantly taking digoxin or other medicinal products that may cause hypomagnesemia (e.g., diuretics), magnesium levels should be checked before starting PPI therapy and periodically during treatment.
Omeprazole may cause severe skin reactions. Symptoms may include skin redness, blisters, and rash. If an allergic reaction occurs, treatment should be discontinued and medical advice sought.
Severe cutaneous adverse reactions (SCAR), including Stevens–Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP), have been reported during omeprazole use, which may be life-threatening or fatal.
Therapy with proton pump inhibitors, particularly at high doses and for prolonged periods (>1 year), may be associated with a small increased risk of fractures of the spine, wrist, and hip, primarily in elderly patients and those with additional risk factors. According to observational studies, PPIs increase the overall risk of fractures by 10–40%. Patients at risk of progressive osteoporosis or osteoporotic fracture should be advised appropriate clinical monitoring according to current clinical guidelines for this condition and should consume adequate amounts of vitamin D and calcium.
Subacute cutaneous lupus erythematosus (SCLE)
PPI use has occasionally been associated with the development of subacute cutaneous lupus erythematosus. If skin manifestations appear, especially in sun-exposed areas, and are accompanied by arthralgia, immediate medical consultation is required and discontinuation of omeprazole should be considered. A history of subacute cutaneous lupus erythematosus following PPI use may increase the risk of developing SCLE when other PPIs are used.
Renal function impairment
Acute tubulointerstitial nephritis (ATIN) has been observed in patients taking omeprazole and may occur at any time during omeprazole therapy (see section "Adverse reactions"). Acute tubulointerstitial nephritis may progress to renal failure. If ATIN is suspected, omeprazole should be discontinued and appropriate treatment initiated immediately.
Effect on diagnostic test results
During treatment with antisecretory drugs, plasma gastrin concentration increases due to reduced gastric acid secretion. As a result of reduced acid secretion, chromogranin A (CgA) levels increase. Elevated CgA levels may interfere with tests for detecting neuroendocrine tumors. To avoid such interference, PPIs should be discontinued at least 5 days before measuring CgA levels (see section "Pharmacodynamics"). 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 therapy.
For treatment of chronic conditions, the drug should not be used in children for longer than recommended.
The medicinal product contains sucrose (in the sugar spheres) as an excipient; therefore, patients with diagnosed intolerance to certain sugars should consult their physician before taking this medicinal product.
PPI therapy slightly increases the risk of gastrointestinal infections caused by Salmonella and Campylobacter, and possibly also Clostridium difficile in hospitalized patients (see section "Pharmacodynamics").
As with any long-term therapy, particularly if duration exceeds 1 year, the patient's condition should be monitored.
The medicinal product contains carmoisine (E 122) and tartrazine (E 102), which may cause allergic reactions.
Use during pregnancy or breastfeeding.
Pregnancy
Results from three prospective epidemiological studies (over 1000 outcomes) indicate no negative effects of omeprazole on pregnancy or fetal/neonatal health; therefore, the drug may be used during pregnancy.
Breastfeeding
Omeprazole passes into breast milk, but is unlikely to affect the infant when used at therapeutic doses.
Fertility
Preclinical studies (animal studies) using the racemic mixture of oral omeprazole do not indicate effects on fertility.
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. However, adverse reactions such as dizziness and visual disturbances may occur (see section "Adverse reactions"). If such disorders occur, patients should not drive or operate machinery.
Dosage and Administration
Dosage
Adults
Treatment of duodenal ulcer
The recommended dose for patients with active duodenal ulcer is 20 mg of omeprazole once daily. In most patients, healing of the duodenal ulcer occurs within 2 weeks. For patients who do not achieve complete healing after the initial course, an additional 2 weeks of treatment is recommended. For patients with poor response to therapy, the recommended dose is 40 mg of omeprazole per day; 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 possible, the recommended dose is 20 mg of omeprazole once daily. In some patients, a daily dose of 10 mg* may be sufficient. If treatment is ineffective, the dose may be increased to 40 mg.
Treatment of gastric ulcers
The recommended dose is 20 mg of omeprazole once daily. In most patients, healing of the gastric ulcer occurs within 4 weeks. Patients who do not achieve complete healing after the initial course should be treated for an additional 4 weeks. In severe cases or cases of recurrence, 40 mg of omeprazole once daily is recommended, with healing usually achieved within 8 weeks.
Prevention of recurrence of gastric ulcers
For prevention of recurrence in patients with gastric ulcer and inadequate response to treatment, the recommended dose is 20 mg of omeprazole once daily. If necessary, the dose may be increased to 40 mg of omeprazole once daily.
Eradication of H. pylori in peptic ulcer disease
For eradication of H. pylori when selecting antibacterial agents, individual drug tolerance, relevant national and local guidelines and treatment recommendations 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.
For each regimen, if the patient remains H. pylori-positive after treatment, 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, healing occurs within 4 weeks. In patients not fully healed after the initial course, healing usually occurs during an additional 4-week treatment period.
Prevention of gastric and duodenal ulcers associated with NSAID use in patients at risk
For prevention of gastric and duodenal ulcers associated with NSAID use in patients at 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.
Treatment of 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 an additional 4 weeks. For patients with severe esophagitis, 40 mg of omeprazole per day is recommended, with healing usually occurring within 8 weeks.
Long-term treatment of patients with healed reflux esophagitis
For long-term treatment of patients with GERD, the recommended dose is 10 mg* 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 be further evaluated.
Treatment of Zollinger-Ellison syndrome
For patients with Zollinger-Ellison syndrome, dosage should be individually adjusted. Treatment continues until clinical manifestations of the disease disappear. The recommended initial dose is 60 mg of omeprazole once daily. Observations in more than 90% of patients with severe disease and inadequate response to other treatments have shown the effectiveness of maintenance therapy at doses of 20–120 mg per day. Daily doses exceeding 80 mg should be divided and administered in two doses.
Children
Children aged 1 year and older with body weight ≥ 10 kg
Treatment of reflux esophagitis
Symptomatic treatment of heartburn and acid regurgitation in GERD
Dosing recommendations:
| Age |
Body weight |
Dosage |
| ≥ 1 year |
10−20 kg |
10 mg* once daily. The dose may be increased to 20 mg once daily if necessary. |
| ≥ 2 years |
> 20 kg |
20 mg once daily. The dose may be increased to 40 mg once daily if necessary. |
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 outcome is not achieved after 2−4 weeks, the patient should be further examined.
Children aged 4 years and adolescents.
Treatment of duodenal ulcer caused by H. pylori
Selection of the appropriate combination therapy 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 agents should also be considered. Treatment should be conducted under medical supervision.
Dosing recommendations:
| Body weight |
Dosage |
| 15–30 kg |
Combination with two antibiotics: Omeprazole 10 mg* + amoxicillin 25 mg/kg body weight + clarithromycin 7.5 mg/kg body weight. Take the drugs together twice daily for 1 week |
| 31–40 kg |
Combination with two antibiotics: Omeprazole 20 mg + amoxicillin 750 mg + clarithromycin 7.5 mg/kg body weight. Take the drugs together twice daily for |
| > 40 kg |
Combination with two antibiotics: Omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg. Take the drugs together twice daily for 1 week |
* If a dose of 10 mg is required, administer the drug in the appropriate dosage form.
Special patient populations
Renal impairment
Dose adjustment is not required in patients with impaired renal function (see section "Pharmacokinetics").
Hepatic impairment
In patients with impaired liver function, a daily dose of 10*–20 mg is sufficient (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), 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 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 taken immediately after preparation or within 30 minutes. The mixture should be shaken before administration and followed with half a glass of water.
Alternatively, patients may suck the capsule and swallow the granules, followed by half a glass of water. The enteric-coated granules should not be chewed.
Children
The medicinal product may be used in children aged 1 year and older with a body weight exceeding 10 kg, under medical supervision, for the treatment of reflux esophagitis, symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease (GERD), and in children aged 4 years and older for the treatment of H. pylori-associated duodenal ulcer, under medical supervision.
Overdose
Human data on omeprazole overdose are very limited. Doses up to 560 mg of omeprazole have been described in the scientific literature, and there have been isolated reports of single oral doses reaching 2400 mg of 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.
However, all reported symptoms were transient, and no serious consequences were reported. Elimination rate of the drug was not altered (first-order kinetics) with increasing dose. If necessary, symptomatic treatment should be administered.
Adverse Reactions.
Summary of safety profile
The most commonly reported adverse reactions (in 1–10% of patients) are headache, abdominal pain, constipation, diarrhoea, bloating and nausea/vomiting.
Severe cutaneous adverse reactions (SCAR) have been reported with omeprazole, including Stevens-Johnson syndrome, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) (see section "Special precautions").
The adverse reactions listed below have been identified or suspected during clinical trials or post-marketing use of omeprazole. These were found not to be dose-dependent. Adverse reactions are categorized by organ systems. Frequencies are defined as follows: very common (≥ 1/10); common (≥ 1/100, < 1/10); uncommon (≥ 1/1000, < 1/100); rare (≥ 1/10000, < 1/1000); very rare (< 1/10000); frequency not known (cannot be estimated from available data).
Blood and lymphatic system disorders:
Rare: leucopenia, thrombocytopenia.
Very rare: agranulocytosis, pancytopenia.
Immune system disorders:
Rare: hypersensitivity reactions, including fever, angioedema, and anaphylactic reactions/shock.
Metabolism and nutrition disorders:
Rare: hyponatremia.
Frequency not known: hypomagnesemia; severe hypomagnesemia may lead to hypocalcemia. Hypomagnesemia associated with hypokalemia.
Psychiatric disorders:
Uncommon: insomnia.
Rare: agitation, confusion, depression.
Very rare: aggression, hallucinations.
Nervous system disorders:
Common: headache.
Uncommon: dizziness, paraesthesia, somnolence.
Rare: taste disturbance.
Eye disorders:
Rare: blurred vision (see section "Ability to influence reaction rate when driving or operating machinery").
Ear and labyrinth disorders:
Uncommon: vertigo (see section "Ability to influence reaction rate when driving or operating machinery").
Respiratory, thoracic and mediastinal disorders:
Rare: bronchospasm.
Gastrointestinal disorders:
Common: abdominal pain, constipation, diarrhoea, flatulence, nausea/vomiting, benign fundic gland polyps.
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 (AGEP), 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 (see section "Special precautions").
Musculoskeletal and connective tissue disorders:
Uncommon: fractures of the hip, wrist or spine.
Rare: arthralgia, myalgia.
Very rare: muscle weakness.
Renal and urinary disorders:
Rare: tubulointerstitial nephritis (with possible progression to renal failure).
Reproductive system and breast disorders:
Very rare: gynaecomastia.
General disorders and administration site conditions:
Uncommon: malaise, peripheral oedema.
Rare: increased sweating.
Children
The safety of omeprazole has been evaluated in 310 children aged 0 to 16 years with acid-related disorders. Limited data are available on long-term safety in 46 children who received maintenance therapy with omeprazole for the treatment of severe erosive esophagitis over 749 days. The adverse reaction profile was similar to that observed in adults during short- and long-term treatment. There are no data on the long-term or delayed effects of omeprazole treatment on sexual maturation and growth.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua
Shelf life: 3 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 30 °C.
Keep out of reach of children.
Packaging. 10 capsules per blister, 10 blisters per carton.
Prescription status. Prescription only.
Manufacturer.
Flamingo Pharmaceuticals Ltd.
Manufacturer's address and place of business.
E-28, Opp. Fire Brigade, MIDC, Talodha, Raigad District, Maharashtra, IN-410 208, India.
Marketing Authorisation Holder.
Ananta Medicare Ltd.
Address of the Marketing Authorisation Holder and/or its representative.
Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.