Instructions for Omeprazole-Darnitsa capsules 20 mg No. 10
Composition
active ingredient: omeprazole;
1 capsule contains omeprazole pellets (equivalent to omeprazole) 20 mg;
Excipients: mannitol (E 421), hypromellose, methacrylate copolymer dispersion, sodium lauryl sulfate, sodium hydrogen phosphate anhydrous, diethyl phthalate, sucrose, titanium dioxide (E 171), povidone, calcium carbonate, talc, polysorbate-80, sodium hydroxide.
Dosage form
Capsules. Capsules contain pellets.
Main physicochemical properties: hard gelatin capsules with a dark red opaque body and an opaque cap of dark gray or black color, containing spherical granules from white to white with a creamy pink tint.
Pharmacotherapeutic group
Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. Proton pump inhibitors. ATC code A02B C01.
Pharmacological properties
Pharmacodynamics
Omeprazole is an antiulcer antisecretory drug. It easily penetrates the parietal cells of the gastric mucosa, concentrates in them and is activated at an acidic pH. The active metabolite, sulfenamide, inhibits the H+, K+-ATPase of the secretory membrane of the parietal cells (proton pump), stopping the release of hydrogen ions into the gastric cavity and blocking the final stage of hydrochloric acid secretion. It dose-dependently reduces the level of basal and stimulated secretion, the total volume of gastric secretion and the release of pepsin. It effectively inhibits both night and day production of hydrochloric acid.
It has a bactericidal effect on Helicobacter pylori (H. pylori). Eradication of H. pylori with the simultaneous use of omeprazole and antibiotics allows you to quickly relieve the symptoms of the disease, achieve a high degree of healing of the affected mucosa and stable long-term remission, and reduces the likelihood of bleeding from the digestive tract.
In reflux ulcerative esophagitis, normalization of acid exposure in the esophagus and maintenance of intragastric pH > 4.0 for 24 hours with a decrease in the destructive properties of gastric contents (inhibition of the transition of pepsinogen to pepsin) contributes to the relief of symptoms and complete healing of esophageal lesions (healing rate exceeds 90%). Highly effective in the treatment of severe and complicated forms of erosive and ulcerative esophagitis resistant to H2-blockers of histamine receptors. Long-term maintenance therapy prevents relapses of reflux esophagitis and reduces the risk of complications.
Pharmacokinetics
After oral administration, the drug is rapidly and significantly absorbed from the digestive tract, however, bioavailability is no more than 50-55% (the effect of "first pass" through the liver). Binding to blood plasma proteins (albumin and acid alpha1-glycoprotein) is very high - 95%.
After a single dose of 20 mg omeprazole, inhibition of gastric secretion occurs within the first hour, reaches a maximum after 2 hours and lasts for approximately 24 hours, the manifestations of the effect depend on the dose. The ability of parietal cells to produce hydrochloric acid is restored within 3-5 days after the end of therapy.
The drug is transformed in the liver with the formation of at least 6 metabolites, characterized by the practical absence of antisecretory activity.
Excreted mainly by the kidneys in the form of metabolites (72-80%) and through the intestines
(18-23%). The half-life is 0.5-1 hour (with normal liver function) or 3 hours (with chronic liver disease).
In elderly patients, a slight increase in bioavailability and a decrease in the rate of excretion are possible.
Indication
Benign gastric ulcer and duodenal ulcer, including those associated with the use of nonsteroidal anti-inflammatory drugs; eradication of Helicobacter pylori (as part of combination therapy with antibacterial agents); gastroesophageal reflux disease; prevention of aspiration of acidic gastric contents; Zollinger-Ellison syndrome; relief of symptoms of acid-dependent dyspepsia.
Contraindication
Hypersensitivity to omeprazole, substituted benzimidazoles or to any of the other ingredients of the drug. Omeprazole, like other proton pump inhibitors, should not be taken with nelfinavir and atazanavir.
Interaction with other medicinal products and other types of interactions
Effect of omeprazole on the pharmacokinetics of other drugs.
Drugs whose absorption depends on the pH of the stomach.
Suppression of gastric secretion during treatment with omeprazole and other PPIs (proton pump inhibitors) 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 during treatment with omeprazole. Concomitant administration of omeprazole (20 mg/day) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10% (in two out of ten subjects – up to 30%).
Plasma levels of nelfinavir and atazanavir are decreased when co-administered with omeprazole.
Concomitant use of omeprazole and nelfinavir is contraindicated. Concomitant use 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/day) 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. Therapeutic drug monitoring of digoxin should be intensified.
Clopidogrel.
In a crossover clinical study, clopidogrel (300 mg loading dose, then 75 mg/day) was administered as monotherapy and with omeprazole (80 mg concomitantly with clopidogrel) for 5 days. When clopidogrel and omeprazole were administered together, the exposure to the active metabolite of clopidogrel was reduced by 46% (day 1) and 42% (day 5). The mean inhibition of platelet aggregation was reduced by 47% (after 24 hours) and 30% (day 5) when clopidogrel and omeprazole were administered together. In another study, it was shown that taking clopidogrel and omeprazole at different times did not interfere with their interaction, which is likely due to the inhibitory effect of omeprazole on CYP2C19. Conflicting data regarding the clinical manifestations of this PK/PD interaction in terms of major cardiovascular diseases have been reported in observational and clinical studies.
Other medicines.
The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced, therefore clinical efficacy may be reduced. Concomitant use of the medicinal product with posaconazole and erlotinib should be avoided.
Drugs 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 include R-warfarin and other vitamin K antagonists, cilostazol, diazepam and phenytoin.
In healthy volunteers, a pharmacokinetic/pharmacodynamic interaction was observed between clopidogrel (loading dose 300 mg/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 (ADP-induced) on platelet aggregation. The clinical significance of this interaction remains unknown. As a precautionary measure, 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 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 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.
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 the tacrolimus dosage should be adjusted if necessary.
Increased methotrexate levels have been reported in some patients when co-administered with proton pump inhibitors. If high doses of methotrexate are required, temporary withdrawal of omeprazole should be considered.
Effect of other drugs on the pharmacokinetics of omeprazole.
Since omeprazole is metabolised by CYP2C19 and CYP3A4, medicinal products known to inhibit CYP2C19 or CYP3A4, or both (e.g. 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/or CYP3A4 inducers.
Drugs known to induce the activity of CYP2C19 or CYP3A4, or both enzymes (e.g. rifampicin and St. John's wort), may lead to decreased serum levels of omeprazole as a result of increased metabolic rate.
Application features
If patients with gastric ulcer or suspected gastric ulcer develop alarming symptoms such as significant weight loss not caused by diet, frequent vomiting, dysphagia, vomiting with blood or melena, the presence of malignant disease should be excluded, since taking the drug may mask its symptoms and delay the diagnosis.
Concomitant use of atazanavir with proton pump inhibitors is contraindicated.
Omeprazole, like other acid-inhibiting substances, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account when treating patients with vitamin B12 deficiency or at risk of reduced vitamin B12 absorption during long-term therapy. In individual cases, monitoring of vitamin B12 plasma levels may be appropriate.
Omeprazole is an inhibitor of CYP2C19. When initiating or ending treatment with omeprazole, the potential for interactions with drugs metabolized by CYP2C19, such as clopidogrel, should be considered.
For the treatment of chronic diseases in children, the drug should not be used for longer than recommended.
Taking proton pump inhibitors may lead to a slightly increased risk of infectious diseases of the digestive tract caused by pathogens such as Salmonella and Campylobacter.
During long-term therapy, especially in cases where the treatment period exceeds 1 year, patients should be under regular medical supervision and undergo laboratory determination of magnesium and calcium in serum.
There are reports of an increased risk of hypomagnesemia with long-term use of omeprazole (1 year or more) at usual doses of 20-40 mg per day.
After discontinuation of the drug, serum magnesium levels returned to normal values. The clinical picture of hypomagnesemia is characterized by: increased neuromuscular excitability, which is manifested by spasm of the muscles of the hands and feet, motor excitement; tachycardia, cardiac arrhythmia, increased blood pressure; dystrophic disorders in the form of trophic erosions and skin ulcers. The criterion for diagnosing hypomagnesemia is a decrease in the concentration of magnesium in the blood serum of less than 1 mEq/l. In addition, cases have been identified when hypomagnesemia led to the development of hypocalcemia, caused by inhibition of parathyroid hormone secretion in conditions of low magnesium content in the body. Some patients experienced severe hypocalcemia and hypomagnesemia, accompanied by the development of convulsive syndrome, cardiac arrhythmias, tetany, mental disorders, and severe vomiting, leading to deterioration of electrolyte balance.
Ability to influence reaction speed when driving vehicles or other mechanisms
The effect of the drug on the ability to drive or operate machinery is unlikely, but the possibility of side effects such as dizziness and visual disturbances should be taken into account.
Use during pregnancy or breastfeeding
The results of studies have not revealed any negative effects of omeprazole during pregnancy on the health of the fetus/newborn child. The drug can be used during pregnancy if, in the opinion of the doctor, the expected benefit to the mother outweighs the possible risk to the fetus.
Omeprazole is excreted in small amounts in breast milk, but its effect on the child is unknown. Therefore, breastfeeding should be discontinued during the period of use of the drug.
Method of administration and doses
It is taken orally before or during meals, without chewing or damaging the capsule, with a small amount of liquid. The dosage regimen depends on the type and severity of the disease and is set by the doctor individually for each patient.
Adults and children over 12 years old.
Treatment and prevention of duodenal and gastric ulcers, as well as gastroduodenal erosion and dyspeptic symptoms associated with the use of nonsteroidal anti-inflammatory drugs: the recommended daily dose is 20 mg. The course of treatment is 4-8 weeks.
For eradication of Helicobacter pylori: omeprazole is prescribed in a daily dose of 40 mg (20 mg 2 times a day) as part of complex therapy according to approved international regimens:
"Triple" therapy for duodenal ulcer: for 1 week 2 times a day: amoxicillin 1 g and clarithromycin 500 mg; for 1 week 2 times a day: clarithromycin 250 mg and metronidazole 400 mg (or tinidazole 500 mg); for 1 week 3 times a day: amoxicillin 500 mg and metronidazole 400 mg.
"Dual" therapy for duodenal ulcer: for 2 weeks 2 times a day: amoxicillin 750 mg-1 g; for 2 weeks 3 times a day: clarithromycin 500 mg.
"Dual" therapy for stomach ulcers: amoxicillin 2 times a day for 2 weeks
750 mg – 1 g.
Gastroesophageal reflux disease: daily dose – 1 capsule, course of treatment – 4-8 weeks. Patients with reflux esophagitis resistant to treatment are prescribed 2 capsules daily for 8 weeks.
Prevention of aspiration of acidic gastric contents: the recommended dose of omeprazole is 40 mg the evening before and 40 mg 2-6 hours before anesthesia.
Zollinger-Ellison syndrome: the initial dose of omeprazole, administered once in the morning, is 60 mg/day; if necessary, the daily dose is increased to 80-120 mg. The dose should be selected individually, taking into account the body's response. If the daily dose exceeds 80 mg, it should be divided into 2-3 doses.
Acid-dependent dyspepsia: the daily dose is 10-20 mg once a day for 2-4 weeks. If after 4 weeks the symptoms do not disappear or quickly reappear, the patient's diagnosis should be reviewed. If it is necessary to use omeprazole in a single dose of less than 20 mg, a drug with a lower content of the active substance is used.
No dose adjustment of omeprazole is required in the elderly or in patients with renal impairment.
In patients with impaired liver function, the maximum daily dose of omeprazole is 20 mg.
Children. In this dosage form, omeprazole is used in children aged 5 years and older with a body weight of at least 20 kg.
For reflux esophagitis, the course of treatment is 4-8 weeks;
for symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease – 2-4 weeks. The daily dose is 20 mg, if necessary, the daily dose can be increased to 40 mg.
If the child is unable to swallow the capsule, it should be opened and the contents mixed with a small amount of apple juice or yogurt (approximately 10 ml). It is important to ensure that the child swallows this mixture immediately after preparation.
It is possible to use omeprazole as part of complex therapy for the eradication of Helicobacter pylori in children aged 5 years and older, but this therapy should be carried out with extreme caution under the close supervision of a physician. The course of treatment is 7 days, if necessary, the course of treatment is extended to 14 days.
Treatment regimen:
children weighing 30-40 kg: omeprazole 20 mg, amoxicillin 750 mg, clarithromycin
7.5 mg/kg body weight 2 times a day for 7 days;
children weighing more than 40 kg: omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg 2 times a day for 7 days.
Children
The drug is used in children over 5 years of age as prescribed by a doctor for reflux esophagitis and symptomatic treatment of heartburn and acid regurgitation in gastroesophageal reflux disease and for the treatment of duodenal ulcers caused by the presence of H. pylori, under the supervision of a doctor.
Overdose
Very limited data are available on the effects of omeprazole overdose in humans. Doses up to 560 mg omeprazole have been described in the literature and there have been isolated reports of single oral doses of 2400 mg omeprazole (120 times the usual recommended clinical dose). Nausea, vomiting, dizziness, abdominal pain, diarrhoea and headache have been reported. Apathy, depression and confusion have also been reported in isolated cases.
The symptoms described are transient in nature. The rate of elimination does not change (first-order kinetics) with increasing dose.
Treatment. There is no specific antidote. It is poorly removed by dialysis. Gastric lavage, symptomatic and supportive therapy are indicated.
Adverse reactions
The most common side effects are headache, abdominal pain, constipation, diarrhea, bloating, and nausea/vomiting.
The following frequency criteria are used to assess adverse reactions: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10,000, < 1/1000), very rare (< 1/10,000), frequency unknown (cannot be estimated due to lack of data).
On the part of the organs of vision: rarely - blurred vision, visual impairment.
From the side of the organs of hearing and vestibular apparatus: infrequently - vertigo.
From the respiratory system, thoracic organs and mediastinum: rarely - bronchospasm.
From the liver and biliary tract: infrequently - increased activity of liver enzymes; rarely - hepatitis, accompanied or not accompanied by jaundice; very rarely - hepatic failure, encephalopathy in patients with known severe liver dysfunction.
Renal and urinary disorders: rarely - interstitial nephritis.
From the side of metabolism: rarely - hyponatremia; frequency unknown - hypomagnesemia, hypocalcemia.
From the nervous system: often - headache; infrequently - dizziness, paresthesia, sleep disturbances, feeling of weakness, drowsiness; rarely - taste disturbances.
On the part of the psyche: infrequently - insomnia; rarely - anxiety, slight disorientation, depression; very rarely - aggression, hallucinations.
From the blood and lymphatic system: rarely - thrombocytopenia, leukopenia; very rarely - agranulocytosis, pancytopenia.
Immune system disorders: Rare: hypersensitivity reactions such as fever, angioedema and anaphylactic reaction/shock.
Skin and subcutaneous tissue disorders: infrequently - dermatitis, hyperemia, itching, rash, urticaria; rarely - alopecia, photosensitivity; very rarely - erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: rarely - arthralgia, myalgia; very rarely - muscular weakness.
From the reproductive system and mammary gland function: very rarely - impotence, gynecomastia.
Other: infrequently - malaise, peripheral edema; rarely - excessive sweating.
The adverse event profile observed in children is consistent with that seen in adults, both during short-term and long-term therapy.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
10 capsules in a contour blister pack; 1 contour blister pack in a pack.
Vacation category
According to the recipe.
Producer
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the manufacturer and its business address
Ukraine, 02093, Kyiv, Boryspilska St., 13.
