Instructions for Omez capsules 10 mg No. 30
Composition
active ingredient: omeprazole;
1 capsule contains omeprazole 10 mg;
Excipients: mannitol (E 421), crospovidone, poloxamer, hydroxypropylmethylcellulose, meglumine, povidone, methacrylate copolymer (type C), triethyl citrate, magnesium stearate.
Dosage form
Capsules.
Main physicochemical properties: off-white to light yellow elliptical and/or spherical shaped pellets in a size “3” hard opaque gelatin capsule with a lavender cap and yellow body with black inscription “OMEZ 10” on the cap and body of the capsule.
Pharmacotherapeutic group
Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors.
ATX code A02B C01.
Pharmacological properties
Pharmacodynamics
Mechanism of action: Omeprazole, a racemic mixture of two enantiomers, reduces gastric acid secretion by a targeted mechanism of action. It is a specific inhibitor of the gastric proton pump in parietal cells. It acts rapidly and provides control of gastric acid suppression with once-daily dosing.
Omeprazole is a weak base that is concentrated and converted to the active form in the acidic environment of the intracellular tubules in parietal cells, where it inhibits the enzyme H+K+-ATPase - the acid pump. This effect on the final stage of the process of gastric acid formation 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 can be explained by the effect of omeprazole on acid secretion.
Effect on gastric acid secretion.
Oral administration of 20 mg omeprazole once daily causes rapid and effective inhibition of daytime and nighttime gastric acid secretion, with the maximum effect being achieved within 4 days of treatment. In patients with duodenal ulcer, a mean reduction in gastric acidity of approximately 80% occurs within 24 hours after taking 20 mg omeprazole, and a mean reduction in peak acid output after pentagastrin stimulation is approximately 70% 24 hours after taking omeprazole.
Oral administration of 20 mg omeprazole maintains an intragastric pH of ≥ 3 in patients with duodenal ulcer for a mean of 17 hours out of a 24-hour period. Omeprazole reduces/normalizes esophageal acid exposure in patients with gastroesophageal reflux disease in a dose-dependent manner by reducing acid secretion and intragastric acidity. The inhibition of acid secretion is associated with the area under the plasma concentration-time curve (AUC) of omeprazole and not with the actual plasma concentration at that time.
No tachyphylaxis was observed during treatment with omeprazole.
Effect on Helicobacter pylori (H. pylori).
Peptic ulcers are associated with H. pylori, including duodenal ulcers and gastric ulcers. H. pylori is considered a major determinant in the development of gastritis. H. pylori, together with gastric acid, are major factors in the development of peptic ulcer disease. H. pylori is a major factor in the development of atrophic gastritis, which is associated with an increased risk of gastric cancer.
Eradication of H. pylori with omeprazole and antimicrobials is associated with more rapid symptom relief, a high rate of mucosal healing, and long-term remission of peptic ulcer disease.
Other effects related to acid suppression.
A slightly increased incidence of gastric glandular cysts has been reported during long-term treatment. These changes are a physiological consequence of the existing inhibition of acid secretion, are benign and probably reversible.
Reducing stomach acid by any means, including proton pump inhibitors, increases the number of bacteria in the stomach that are normally present in the gastrointestinal tract. Treatment with acid-reducing drugs slightly increases the risk of gastrointestinal infections, such as those caused by Salmonella, Campylobacter, and Clostridium difficile in hospitalized patients.
Application in pediatrics.
In an uncontrolled study in children (aged 1 to 16 years) with severe erosive esophagitis, omeprazole at doses of 0.7–1.4 mg/kg improved the condition of patients with esophagitis in 90% of cases and significantly reduced reflux symptoms. In a blinded, non-comparative study in children aged 0 to 24 months with established gastroesophageal reflux disease treated with doses of 0.5 mg/kg, 1.0 mg/kg and 1.5 mg/kg of omeprazole, the frequency of vomiting/regurgitation episodes was reduced by 50% after 8 weeks of treatment regardless of dose.
A randomized, double-blind clinical trial (Héliot study) concluded that omeprazole in combination with two antibiotics (amoxicillin and clarithromycin) was safe and effective in the treatment of H. pylori infection in children aged 4 years and older with gastritis: H. pylori eradication rate: 74.2% (23/31 patients) in the omeprazole + amoxicillin + clarithromycin group, compared with 9.4% (3/32 patients) in the amoxicillin + clarithromycin group. However, no evidence of clinical benefit was demonstrated for dyspeptic symptoms. This study did not include children aged under 4 years.
Pharmacokinetics
Absorption. Absorption of omeprazole is rapid, with peak plasma levels occurring approximately 1–2 hours after dosing. Absorption of omeprazole occurs in the small intestine and is usually complete within 3–6 hours. Concomitant food intake has no effect on bioavailability. The systemic availability (bioavailability) of omeprazole after a single oral dose of omeprazole is approximately 40%. After repeated once-daily administration, bioavailability increases to approximately 60%.
Distribution: The apparent volume of distribution in healthy subjects is approximately 0.3 l/kg body weight. The plasma protein binding of omeprazole is 97%.
Metabolism: Omeprazole is completely metabolised by the cytochrome P450 system. The majority of omeprazole metabolism is dependent on the expressed CYP2C19, responsible for the formation of hydroxyomeprazole, the major metabolite in plasma. The remainder is dependent on another specific isoform, CYP3A4, responsible for the formation of omeprazole sulfone. As a result of the high affinity of omeprazole for CYP2C19, there is a potential for competitive inhibition and metabolic interactions between drugs with other substrates for CYP2C19. However, due to its low affinity for CYP3A4, omeprazole has no potential to inhibit the metabolism of other CYP3A4 substrates. Furthermore, omeprazole has no inhibitory effect on major CYP enzymes.
Approximately 3% of the Caucasian population and 15–20% of Asian populations lack a functional CYP2C19 enzyme. In these individuals, the metabolism of omeprazole is likely to be primarily catalyzed by CYP3A4. After repeated once-daily administration of 20 mg omeprazole, the mean AUC was 5–10 times higher in poor metabolizers than in individuals with a functional CYP2C19 enzyme (extensive metabolizers). The mean peak plasma concentrations were also 3–5 times higher. These observations have no relevance to the dosing of omeprazole.
Elimination: The terminal half-life of omeprazole from plasma is generally less than 1 hour after both single and multiple once-daily oral administration. Omeprazole is completely eliminated from plasma between doses without a tendency for accumulation during once-daily administration. Approximately 80% of an oral dose of omeprazole is excreted as metabolites in the urine, the remainder in the faeces, mainly via biliary secretion.
With repeated administration, the AUC of omeprazole increases. This increase is dose-dependent and results in a non-linear relationship between dose and AUC after repeated administration. This time- and dose-dependence is associated with a decrease in presystemic metabolism and systemic clearance, possibly due to inhibition of the CYP2C19 enzyme by omeprazole and/or its metabolites (e.g. the sulfone).
The metabolite was not found to have any effect on gastric acid secretion.
Special populations.
Hepatic impairment: In patients with hepatic impairment, the metabolism of omeprazole is altered, leading to an increase in AUC. Omeprazole did not show any tendency for accumulation when administered once daily.
Renal impairment: The pharmacokinetics of omeprazole, including systemic bioavailability and elimination rate, are not altered in patients with reduced renal function.
Elderly patients: The metabolic rate of omeprazole is slightly reduced in elderly patients (75-79 years).
Children: When treated with recommended doses in children from 1 year of age, plasma concentrations were similar to those in adults. In children under 6 months of age, clearance of omeprazole is low due to a low capacity to metabolize omeprazole.
Indication
Dyspeptic syndrome associated with increased acidity of gastric juice, manifested by heartburn, acid regurgitation, and pain in the epigastric region.
Contraindication
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 Interactions with other medicinal products and other forms of interaction).
Interaction with other medicinal products and other types of interactions
Effect of omeprazole on the pharmacokinetics of other drugs.
Inhibition of gastric secretion by omeprazole and other PPIs may reduce or increase the absorption of drugs whose absorption depends on gastric pH. As with other drugs that reduce gastric acidity, the absorption of drugs such as ketoconazole, itraconazole and erlotinib may be reduced, while the absorption of drugs such as digoxin may be increased by omeprazole. Concomitant administration of omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10% (in two out of ten subjects – up to 30%).
Nelfinavir, atazanavir
Plasma levels of nelfinavir and atazanavir are decreased when co-administered with omeprazole.
Concomitant use of omeprazole and nelfinavir is contraindicated. Co-administration of omeprazole (40 mg once daily) decreased the mean exposure of nelfinavir by approximately 40% and the mean exposure of the pharmacologically active metabolite M8 decreased by approximately 75–90%. The interaction may also be due to inhibition of CYP2C19 activity.
Concomitant use of omeprazole with atazanavir is not recommended. Concomitant use of omeprazole (40 mg once daily) and atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a 75% decrease in atazanavir exposure. Increasing the atazanavir dose to 400 mg did not compensate for the effect of omeprazole on atazanavir exposure. Concomitant use of omeprazole (20 mg once daily) with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers resulted in an approximately 30% decrease in atazanavir exposure compared to atazanavir 300 mg/ritonavir 100 mg once daily.
Digoxin
Concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10%. Rare cases of digoxin-induced toxicity have been reported. However, caution should be exercised when prescribing high doses of omeprazole to elderly patients. In case of concomitant use with digoxin, patients should be closely monitored.
Clopidogrel
A clinical study in healthy volunteers showed a pharmacokinetic/pharmacodynamic (PK/PD) interaction between clopidogrel (300 mg loading dose followed by 75 mg/day) and omeprazole (80 mg/day), resulting in a 46% decrease in exposure to the active metabolite of clopidogrel and a 16% decrease in maximal inhibition (induced by adenosine diphosphate (ADP)) of platelet aggregation.
Conflicting data on the clinical consequences of PK/PD interactions with omeprazole in terms of major cardiovascular events have been obtained from both observational and clinical studies. Therefore, concomitant use of omeprazole and clopidogrel should be avoided.
Other medicines
The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced and therefore clinical efficacy may be reduced. Concomitant use with posaconazole and erlotinib should be avoided.
Medicinal products metabolized by CYP2C19
Omeprazole is a moderate inhibitor of CYP2C19, the main enzyme that metabolizes omeprazole. Therefore, the metabolism of concomitant drugs that are also metabolized by CYP2C19 may be reduced and the systemic exposure of these drugs may be increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.
In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg/day orally, i.e. a dose 4 times the standard daily dose), resulting in a mean 46% decrease in exposure to the active metabolite of clopidogrel and a mean 16% decrease in the maximum inhibitory effect (induced by ADP) on platelet aggregation. The clinical significance of this interaction remains unclear. As a precautionary measure, the concomitant use of omeprazole and clopidogrel should be avoided.
Cilostazol
In healthy volunteers, administration of omeprazole at a dose of 40 mg increased the Cmax and AUC of cilostazol by 18% and 26%, respectively, and one of its active metabolites by 29% and 69%, respectively.
Phenytoin
Monitoring of phenytoin plasma concentrations is recommended during the first two weeks after starting treatment with omeprazole and, if phenytoin dose adjustment has been made, monitoring and further dose adjustment of the drug should be carried out after the end of treatment with omeprazole.
Unknown mechanism of interaction
Saquinavir
Concomitant use of omeprazole with saquinavir/ritonavir resulted in an increase in plasma levels of saquinavir of approximately 70%, which was associated with good tolerability in HIV-infected patients.
Tacrolimus
Increased serum tacrolimus levels have been reported with concomitant use of omeprazole. Increased monitoring of tacrolimus concentrations and renal function (creatinine clearance) is required and, if necessary, tacrolimus dosage should be adjusted.
Increased methotrexate levels have been reported in some patients when co-administered with proton pump inhibitors. If high doses of methotrexate are necessary, temporary withdrawal of omeprazole should be considered.
Effect of other drugs on the pharmacokinetics of omeprazole.
CYP2C19 and/or CYP3A4 inhibitors
Since omeprazole is metabolised by CYP2C19 and CYP3A4, drugs that inhibit CYP2C19 or CYP3A4 (such as clarithromycin and voriconazole) may increase omeprazole serum levels by decreasing its metabolic rate. Concomitant use of voriconazole resulted in a more than two-fold increase in omeprazole exposure. Since high doses of omeprazole were well tolerated, dose adjustment of omeprazole is generally not necessary. However, dose adjustment should be considered in patients with severe hepatic impairment and if long-term treatment is indicated.
Omeprazole is also partially metabolized by CYP3A4, but does not inhibit this enzyme. Thus, omeprazole does not affect the metabolism of drugs metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin, and budesonide.
CYP2C19 and CYP3A4 inducers
Drugs that induce CYP2C19 or CYP3A4 activity (such as rifampicin and St. John's wort) may lead to decreased serum levels of omeprazole as a result of an increase in its metabolic rate.
Application features
In the presence of any alarming symptom (e.g. significant weight loss not due to diet; frequent vomiting; dysphagia; vomiting with blood or melena) and when gastric ulcer is diagnosed or suspected, malignant disease should be excluded, since taking the drug may mask its symptoms and delay the establishment of the correct diagnosis.
Concomitant use of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor cannot be avoided, close clinical monitoring (e.g. viral load) is recommended in conjunction with an increase in the dose of atazanavir to 400 mg per 100 mg of ritonavir; the dose of omeprazole should not exceed 20 mg.
Omeprazole, like all drugs that inhibit the secretion of hydrochloric acid in the stomach, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account in patients with cachexia or risk factors for reduced absorption of vitamin B12 during long-term therapy.
Omeprazole is an inhibitor of CYP2C19. When initiating or ending treatment with omeprazole, the possibility of interactions with medicinal products metabolised by CYP2C19 should be considered. An interaction has been observed between clopidogrel and omeprazole (see section 4.5). The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.
Patients taking proton pump inhibitors, including omeprazole, may develop severe hypomagnesemia for at least three months (in most cases of hypomagnesemia, patients have been taking the drug for about a year). Hypomagnesemia can be suspected by such serious manifestations as fatigue, muscle spasms, tetany, seizures, delirium, dizziness, ventricular arrhythmia. However, it should be borne in mind that in some cases the manifestations may be masked, which prevents timely recognition of such a complication. In most patients, the manifestations of hypomagnesemia disappear and the condition normalizes after the use of magnesium preparations and the withdrawal of proton pump inhibitors.
In patients on long-term treatment or taking PPIs with digoxin or drugs that can cause hypomagnesemia (e.g., diuretics), magnesium levels should be measured, if possible, before starting PPI treatment and periodically during treatment.
A prolonged decrease in gastric acidity can lead to an increase in the number of bacteria present in the gastrointestinal tract.
Treatment with proton pump inhibitors slightly increases the risk of gastrointestinal infections caused by Salmonella, Campylobacter, and Clostridium difficile in hospitalized patients.
In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/daily maintenance dose 75 mg) and omeprazole (80 mg/day orally, i.e. a dose 4 times the standard daily dose), resulting in a mean 46% decrease in exposure to the active metabolite of clopidogrel and a mean 16% decrease in the maximum inhibitory effect (induced by ADP) on platelet aggregation.
The use of proton pump inhibitors, especially at high doses and in long-term treatment, may be associated with a small increased risk of fractures, predominantly in the elderly and in the presence of additional risk factors. Although a causal relationship between the use of omeprazole/esomeprazole and osteoporotic fractures has not been proven, appropriate clinical surveillance should be recommended in patients at risk of progressive osteoporosis or osteoporotic fracture, in accordance with current clinical guidelines.
The use of proton pump inhibitors may be associated with very rare cases of PsA. If lesions occur, especially in sun-exposed areas of the skin, and if accompanied by arthralgia, the patient should seek medical advice immediately and the healthcare professional should consider discontinuing omeprazole. If PsA develops after previous treatment with a proton pump inhibitor, the risk of PsA increases with the use of other proton pump inhibitors.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug is unlikely to affect the ability to drive or use machines. Undesirable effects such as dizziness and visual disturbances may occur (see section "Adverse reactions"). If such disorders are observed, patients should not drive or use machines.
Use during pregnancy or breastfeeding
The results of the studies indicate that there is no negative effect on pregnancy, the health of the fetus or the newborn. Omeprazole can be used during pregnancy if the expected benefit to the mother outweighs the possible risk to the fetus. Omeprazole passes into breast milk in small amounts, but its effect on the child is unknown, so breastfeeding should be discontinued during treatment with the drug.
Method of administration and doses
Adults and children aged 12 and over.
The usual recommended dose is 1 or 2 capsules of Omez® once a day, corresponding to 10 mg or 20 mg of omeprazole, for 2–4 weeks, depending on the severity and persistence of symptoms. If there is no relief after 4 weeks or if symptoms recur shortly after, you should consult a doctor.
It is recommended to take the capsules in the morning, preferably before meals, without damaging the capsule (the capsules should not be chewed or broken) and with a small amount of water.
For patients with swallowing difficulties and for children who can drink or swallow semi-solid food. The capsules can be opened and the contents swallowed directly with half a glass of water, or mixed in a slightly acidic liquid, such as any fruit juice or applesauce or unsalted water. This mixture should be drunk immediately after preparation or within 30 minutes. The mixture should be shaken before taking and washed down with half a glass of water. Do not use milk or carbonated water.
Special patient groups.
Renal impairment: No dose adjustment is required for patients with renal impairment (see Pharmacokinetics).
Hepatic impairment: For patients with hepatic impairment, a daily dose of 10–20 mg is sufficient (see Pharmacokinetics).
Elderly patients (> 65 years): No dose adjustment is required for elderly patients (see section 5.2).
Children
The drug is used to treat children over 12 years of age.
Overdose
Data on the effects of omeprazole overdose in humans. There is very limited literature describing doses up to 560 mg of omeprazole, and there are isolated reports of a single oral dose of 2400 mg of omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhea, and headache have been reported. Apathy, depression, and confusion have also been reported in isolated cases.
The described symptoms are transient in nature. The rate of elimination does not change (first-order kinetics) with increasing dose. Treatment, if necessary, is symptomatic.
Adverse reactions
The most common adverse reactions are headache, abdominal pain, constipation, diarrhea, bloating, and nausea/vomiting. The following adverse drug reactions have been identified during clinical trials with omeprazole or during post-marketing use. Adverse reactions are classified according to their effect on organ systems.
From the blood and lymphatic system: leukopenia, thrombocytopenia, agranulocytosis, pancytopenia.
Immune system disorders: hypersensitivity reactions, e.g. fever, angioedema and anaphylactic reaction/shock.
Metabolism and digestion: hyponatremia, hypomagnesemia, severe hypomagnesemia may lead to hypocalcemia. Hypomagnesemia may also be associated with hypokalemia.
On the part of the psyche: insomnia, agitation, confusion, depression, aggression, hallucinations.
From the nervous system: headache, dizziness, paresthesia, drowsiness, taste disturbance.
From the organs of vision: blurred vision.
From the organs of hearing and balance: tinnitus, vertigo.
Respiratory, thoracic and mediastinal disorders: bronchospasm.
Gastrointestinal: abdominal pain, constipation, diarrhea, bloating, nausea/vomiting, dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis, fundic gland polyps (benign).
Skin and subcutaneous tissue disorders: dermatitis, pruritus, rash, urticaria, alopecia, photosensitivity, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, subacute cutaneous lupus erythematosus (see section "Special warnings and precautions for use").
Musculoskeletal system: arthralgia, myalgia, muscle weakness, increased risk of fractures with prolonged use (see section "Special instructions").
Renal and urinary disorders: interstitial nephritis, renal failure.
From the reproductive system and mammary glands: gynecomastia.
General disorders: discomfort, malaise, peripheral edema, increased sweating.
Pediatric patients.
The safety of omeprazole has been evaluated in 310 children aged 0 to 16 years with acid-dependent diseases. There are limited data from long-term safety studies in 46 children who received maintenance therapy with omeprazole for the treatment of severe erosive esophagitis for 749 days. The adverse reaction profile is similar to that in adults with short-term and long-term treatment. There are no long-term data on the effects of omeprazole treatment on puberty and growth.
Expiration date
3 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
10 capsules in a blister, 3 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
Dr. Reddy's Laboratories Ltd.
Location of the manufacturer and its business address
Station No. 41, Bachupali Village, Bachupali Mandal, Medchal Malkaigiri District, Telangana 500090, India.
