Composition, form of production and packaging
Capsules hard gelatinous, transparent, size 2, with a colorless body, pink lid and black marking "OMEZ" on both parts of the capsule; the contents of the capsules are granules of white or almost white color.
1 caps.
omeprazole 20 mg
Excipients:
Granules: mannitol - 143.567 mg, lactose - 10.14 mg, sodium lauryl sulfate - 0.545 mg, sodium hydrophosphate - 0.923 mg, sucrose - 8.951 mg, sucrose (25/30) - 25.524 mg, hypromellose 6 cps - 0.139 mg.
Coverage: hypromellose 6 cps - 10.49 mg.
The enteric coating: a copolymer of methacrylic acid and methyl acrylate (1: 1) (methacrylic acid copolymer (type C)) 37.8 mg, sodium hydroxide 0.504 mg, macrogol 6000 4.536 mg, talc 4.41 mg, titanium dioxide 3.15 mg.
The composition of capsules of gelatinous solid No. 2: propyl parahydroxybenzoate, methylparahydroxybenzoate, sodium lauryl sulfate, water, dye azorubin (E122) (cap capsule), gelatin.
10 pieces. - Strips aluminum (3) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Antiulcer drug.
Mechanism of action
Omeprazole is a weak base. Concentrates in the acidic environment of the secretory tubules of parietal cells of the gastric mucosa, is activated and inhibits the proton pump - the enzyme H + -K + -ATP-ase.
Effect of omeprazole on the last stage of the process of formation of hydrochloric acid in the stomach is dose-dependent and provides a highly effective inhibition of basal and stimulated secretion of hydrochloric acid regardless of the stimulating factor.
Effect on secretion of gastric juice
Omeprazole with a daily oral administration provides a fast and effective inhibition of day and night secretion of hydrochloric acid.
The maximum effect is achieved within 4 days of treatment. In patients with duodenal ulcers, omeprazole at a dose of 20 mg causes a steady decrease in 24-hour gastric acidity by at least 80%. At the same time, the mean C max of hydrochloric acid is reduced after pentagastrin stimulation by 70% within 24 hours.
In patients with duodenal ulcer omeprazole at a dose of 20 mg with a daily oral administration maintains in the intragastric environment the pH value of acidity? 3 on average for 17 hours a day.
The inhibition of the secretion of hydrochloric acid depends on the AUC of omeprazole, and not on the concentration of the drug in the plasma at a given time.
Action on Helicobacter pylori
In vitro, omeprazole has a bactericidal effect against Helicobacter pylori.
Eradication of Helicobacter pylori with omeprazole together with antibacterial agents is accompanied by rapid elimination of symptoms, high healing of defects in the gastrointestinal mucosa and long-term remission of peptic ulcer, which reduces the likelihood of complications such as bleeding, as effectively as constant maintenance therapy.
Other effects associated with inhibition of hydrochloric acid secretion
In patients taking drugs that reduce the secretion of the glands of the stomach, for a long period of time, the formation of glandular cysts in the stomach is more often noted; cysts are benign and pass independently on the background of continuation of therapy.
A decrease in the secretion of hydrochloric acid in the stomach leads to a slight increase in the risk of intestinal infections caused by Salmonella spp., РЎampylobacter spp. and Clostridium difficile.
During treatment with drugs that reduce the secretion of the glands of the stomach, the concentration of gastrin in the blood serum increases. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A increases.
PHARMACOKINETICS
Suction
Omeprazole is rapidly absorbed from the gastrointestinal tract, C max of omeprazole in blood plasma is reached after 0.5-1 hour. Bioavailability after a single oral intake is 30-40%, after a constant intake 1 time / day, bioavailability increases to 60%. Eating does not affect the bioavailability of omeprazole.
Distribution
The binding of omeprazole to plasma proteins is about 95%, V d is 0.3 l / kg.
Metabolism
Part of omeprazole undergoes pre-systemic hepatic metabolism involving isoenzymes CYP2S19 and CYP3A4 with the formation of inactive metabolites of sulfone, sulfide and hydroxyomeprazole. Omeprazole, not included parietal cells in the formation of active metabolites, is completely metabolized in the liver also with the participation of isoenzymes CYP2S19 and CYP3A4.
Excretion
The total plasma clearance is 0.3-0.6 l / min.
T 1/2 is about 40 minutes (30-90 minutes). About 80% is excreted as metabolites by the kidneys, the rest - by the intestine.
Pharmacokinetics in specific patient groups
There were no significant changes in the bioavailability of omeprazole in elderly patients or in patients with impaired renal function.
In patients with impaired liver function, there is an increase in the bioavailability of omeprazole and a significant decrease in plasma clearance.
INDICATIONS
Adults
- Stomach ulcer and duodenal ulcer (including the prevention of relapses);
- gastroesophageal reflux disease (GERD);
- hypersecretory conditions (Zollinger-Ellison syndrome, stress ulcers of the gastrointestinal tract, multiple endocrine adenomatosis, systemic mastocytosis);
- eradication of Helicobacter pylori in infected patients with peptic ulcer of stomach and duodenum (as part of combination therapy);
- prevention and treatment of damage to the mucous membrane of the stomach and duodenum caused by the intake of NSAIDs (NSAIDs): dyspepsia, erosion of the mucous membrane, peptic ulcer;
- Prevention of Mendelssohn syndrome (aspiration pneumonitis).
Children
- therapy of gastroesophageal reflux disease in children over 2 years old, with a body weight of more than 20 kg;
- therapy of duodenal ulcer caused by Helicobacter pylori in children over the age of 4, with a body weight of more than 20 kg.
The safety and efficacy of the drug in other indications in patients of childhood is not established.
DOSING MODE
The drug is taken orally, 30 minutes before meals, washed down with a sufficient amount of water (the contents of the capsule can not be chewed).
If the patient is not able to swallow the whole capsule, you can mix its contents with slightly acidified liquid, juice or fruit puree. Do not dissolve the contents of the capsule in carbonated drinks or milk. The resulting mixture should be used inside immediately after preparation.
Adults
With peptic ulcer of the stomach and duodenum (including for the prevention of relapses), the drug is prescribed 20 mg once a day; patients resistant to treatment with other antiulcer drugs, Omez В® is prescribed in a dose of 40 mg / day. The course of treatment for duodenal ulcer is 2 weeks, if necessary - up to 4 weeks; with peptic ulcer of the stomach - 4-8 weeks.
In gastroesophageal reflux disease (GERD) , depending on the severity of esophagitis, it is prescribed from 20 mg to 80 mg per day. The duration of the main course also depends on the severity of the esophagitis and is 4-8 weeks. Supportive therapy should be carried out at the lowest effective dose, incl. on demand, with intermittent courses. The duration of maintenance therapy is determined by the doctor.
When hypersecretory conditions (Zollinger-Ellison syndrome, stress ulcers of the gastrointestinal tract, multiple endocrine adenomatosis, systemic mastocytosis), thedrug is prescribed in a dose of 60 mg; if necessary, increase the dose to 80-120 mg / day (in this case, the dose should be divided into 2-3 doses).
For the eradication of Helicobacter pylori in infected patients with peptic ulcer of the stomach and duodenum, according to the recommendations of the working group Maastricht-4, Omez В® can be included in the following treatment regimens:
- the first line (standard triple scheme): Omez В® 20 mg 2 times / day + clarithromycin 500 mg 2 times / day + amoxicillin 1000 mg 2 times / day. To increase the effectiveness of therapy, it is possible to administer Omez В® in a dose of 40 mg (2 capsules to 20 mg) 2 times / day (doubling the standard dose) and increase the duration of the course from 7 to 10-14 days;
- the second line (four-component): it is used when the standard triple therapy is ineffective, or when the penicillin group is intolerant. Bismuth titrate dicitrate (120 mg 4 times / day) in combination with Omez В® preparation 20 mg 2 times / day, tetracycline (500 mg 4 times / day), metronidazole (500 mg 4 times / day) for 10 days;
- the third line and other alternative therapies are prescribed based on the study of the individual sensitivity of Helicobacter pylori to antibacterial drugs.
To prevent and treat damage to the mucous membrane of the stomach and duodenum caused by the intake of NSAIDs (NSAIDs) , such as dyspepsia, mucosal erosion, peptic ulcer, Omez В® is prescribed at a dose of 20 mg daily 30 minutes before breakfast for the entire course of treatment with NSAIDs; with the purpose of treatment - in a dose of 20 mg 2 times / day or 40 mg 1 time / day for 4-8 weeks.
For the prevention of Mendelssohn's syndrome (aspiration pneumonitis) 40 mg are prescribed once.
Children
In patients with gastroesophageal reflux disease, children over 2 years of age, with a body weight of more than 20 kg, are recommended to prescribe Omez В® in a dose of 20 mg once a day for 4-8 weeks (the recommended dose of omeprazole for the treatment of gastroesophageal reflux disease in pediatric practice is 0.7-3.3 mg / kg / day).
With duodenal ulcer caused by Helicobacter pylori, children over the age of 4 years, with a body weight of more than 20 kg, the drug is prescribed in a dose of 20 mg 1 time / day in combination with antibacterial drugs (the recommended dose of omeprazole in Helicobacter pylori eradication schemes in pediatric practice is 1-2 mg / kg / day).
Special patient groups
In patients with impaired renal function, dose adjustment is not required.
In patients with impaired liver function, bioavailability and omeprazole clearance are increased. In this regard, the therapeutic dose should not exceed 20 mg / day.
The rate of metabolism of omeprazole in elderly patients is reduced, but dose adjustment is not required.
SIDE EFFECT
The frequency of unwanted drug reactions is set out in accordance with the following gradation: very often (> 1/10); often (? 1/100, <1/10); infrequently (? 1/1000, <1/100); rarely (? 1/10 000, <1/1000); very rarely (<1/10 000, including isolated cases).
From the hemopoietic system: rarely - leukopenia, thrombocytopenia, hypochromic microcytic anemia in children; very rarely - agranulocytosis, pancytopenia, eosinophilia.
On the part of the immune system: rarely - hypersensitivity reactions (fever, angioedema, anaphylactic reaction / anaphylactic shock).
From the side of metabolism: rarely - hyponatremia; frequency is unknown - hypomagnesemia, which in severe cases can lead to hypocalcemia, hypokalemia.
Disorders of the psyche: infrequently - insomnia; rarely - increased excitability, depression, reversible confusion; very rarely - aggression, hallucinations.
From the nervous system: often - headache; infrequently - dizziness, paresthesia, drowsiness; rarely - a taste disorder.
From the side of the organ of vision: rarely - blurred vision.
From the side of the organ of hearing and labyrinthine disturbances: infrequently - impairment of auditory perception, vertigo.
From the respiratory system: rarely - bronchospasm.
From the GI tract: often - abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting; rarely dry mouth, stomatitis, gastrointestinal candidiasis, microscopic colitis; single cases - the formation of gastric glandular cysts during long-term treatment with simultaneous use with clarithromycin (a consequence of inhibiting the secretion of hydrochloric acid, is benign, reversible).
On the part of the liver and bile ducts: infrequently - increased activity of hepatic enzymes and alkaline phosphatase (reversible nature); rarely - hepatitis (with jaundice or without), hepatic insufficiency, encephalopathy in patients with previous severe liver diseases.
From the skin and subcutaneous tissues: infrequently - dermatitis, itchy skin, skin rash, urticaria; rarely - alopecia, photosensitivity reactions in the form of reddening of the skin after UFD, multiform exudative erythema, toxic epidermal necrolysis, Stevens-Johnson syndrome.
From the musculoskeletal system: infrequently - fractures of the vertebrae, bones of the wrist, head of the femur, associated with osteoporosis; rarely - arthralgia, myalgia, muscle weakness.
From the urinary system: rarely - interstitial nephritis.
From the genitals and the breast: rarely - gynecomastia.
Other: infrequent - malaise; rarely - increased sweating, peripheral edema.
In case of side effects not listed in this manual, the patient should immediately consult a doctor.
CONTRAINDICATIONS
- deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption (due to the presence of sucrose in the formulation);
- simultaneous reception with erlotinibom, posaconazole, nelfinavir and atazanavir;
- use in children other than as indicated by gastroesophageal reflux disease in children over 2 years of age and duodenal ulcer caused by Helicobacter pylori in children older than 4 years;
- Hypersensitivity to omeprazole, substituted benzimidazoles or other components of the drug.
With caution should prescribe the drug for osteoporosis.
PREGNANCY AND LACTATION
The results of the studies showed no side effects of omeprazole on the health of pregnant women, on the fetus or newborn.
Omeprazole is excreted in breast milk, but when applied in therapeutic doses, exposure to the baby is unlikely.
Omeprazole is approved for use during pregnancy and during breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
In patients with impaired renal function, dose adjustment is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired liver function, bioavailability and omeprazole clearance are increased. In this regard, the therapeutic dose should not exceed 20 mg / day.
APPLICATION FOR CHILDREN
Contraindicated use of the drug in children, except for the evidence of gastroesophageal reflux disease in children over 2 years and duodenal ulcer caused by Helicobacter pylori, in children older than 4 years.
APPLICATION IN ELDERLY PATIENTS
The rate of metabolism of omeprazole in elderly patients is reduced, but dose adjustment is not required.
SPECIAL INSTRUCTIONS
In the presence of any anxiety symptoms, such as significant spontaneous weight loss, frequent vomiting, dysphagia, vomiting with blood or melena, and in the presence of a stomach ulcer (or suspected gastric ulcer), the possibility of malignant growth should be excluded, since treatment with Omez В® can lead to a smoothing of the symptoms and delay the diagnosis.
The decrease in the secretion of hydrochloric acid in the stomach under the influence of proton pump inhibitors leads to an increase in the growth of normal intestinal microflora and may lead to a slight increase in the risk of intestinal infections caused by bacteria of the genus Salmonella spp., Campylobacter spp., And also bacteria Clostridium difficile.
Reducing acidity on the background of taking omeprazole can also lead to a decrease in absorption of vitamin B 12 (cyanocobalamin).
With the simultaneous use of omeprazole with clopidogrel, a decrease in the antiplatelet effect of the latter is observed.
Patients with a risk of developing osteoporosis or fractures against it should be under appropriate clinical supervision, although a causal relationship between the use of omeprazole / esomeprazole with fractures against osteoporosis is not established.
There are reports of the emergence of severe hypomagnesemia in patients receiving proton pump inhibitors therapy, including omeprazole, more than one year. Patients receiving omeprazole therapy for a long time, especially in combination with digoxin or other drugs that reduce the magnesium content in the blood plasma (diuretics) require regular monitoring of the magnesium content.
Before using the drug, the patient should consult a doctor in the following cases:
- in the presence of a previously diagnosed gastric ulcer, severe liver disease accompanied by hepatic insufficiency, renal failure, jaundice, previous surgical intervention on the gastrointestinal tract;
- in the presence of anxiety symptoms (significant spontaneous weight loss, repeated vomiting, vomiting with blood, a change in color of stool (tarry stool - melena), impaired swallowing);
- with the appearance of new symptoms or a change in the already existing symptoms from the gastrointestinal tract;
- with simultaneous use with one or more of the following drugs (clopidogrel, digoxin, ketoconazole, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, clarithromycin, voriconazole, rifampicin, St. John's wort preparations).
Impact on laboratory tests
A decrease in the level of hydrochloric acid secretion can lead to an increase in the concentration of chromogranin A (CgA), which affects the results of the examinations for the detection of neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors should be suspended 5 days before the study of the concentration of CgA.
Impact on the ability to drive vehicles and manage mechanisms
During treatment with omeprazole, dizziness, drowsiness, and visual impairment may occur, therefore, care should be taken when driving vehicles and performing other potentially dangerous activities requiring increased concentration of attention and speed of psychomotor reactions.
OVERDOSE
Symptoms: confusion, blurred vision, drowsiness, dry mouth, headache, nausea, tachycardia, arrhythmia.
Treatment: symptomatic therapy, hemodialysis is not effective enough.
DRUG INTERACTION
Means a pH-dependent absorption
Like other drugs, lowering gastric acidity, omeprazole treatment may result in decreased absorption of ketoconazole, itraconazole, posaconazole, erlotinib, iron and cyanocobalamin. Combined use should be avoided with omeprazole.
Digoxin
bioavailability of digoxin while the use of omeprazole is increased by 10% (may require correction mode digoxin). Caution must be exercised while the use of these drugs in elderly patients.
clopidogrel
According to the research mentioned interaction between clopidogrel (300 mg loading dose, a maintenance dose of 75 mg / day) and omeprazole (80 mg / day orally), which reduces the exposure of the active metabolite of clopidogrel and reduce platelet aggregation inhibition. Probably, the observed effect is due to the inhibitory effect of omeprazole on isoenzyme CYP2C19. Therefore, you should avoid the simultaneous use of omeprazole and clopidogrel.
antiretrovirals
The increase in pH during treatment with omeprazole may interfere with the absorption of antiretroviral drugs. It is also possible for the interaction CYP2C19 isozyme level. If concomitant use of omeprazole and certain antiretroviral drugs such as atazanavir and nelfinavir, against the background of omeprazole therapy, there is a decrease in their serum concentrations. While the use of omeprazole is reduced by 75% AUC atazanavir. In this connection, the combined use of omeprazole with antiretroviral drugs such as nelfinavir and atazanavir, is contraindicated.
While the use of omeprazole marked increase in plasma concentrations of saquinavir / ritonavir to 70%, while the patients tolerated the treatment of HIV infection is not deteriorated.
tacrolimus
With simultaneous use of omeprazole and tacrolimus was observed increase of tacrolimus concentrations in blood serum, which may require correction of the dose. It is necessary to control the spacecraft and the concentration of tacrolimus in the blood plasma by combining it with omeprazole.
Methotrexate
When combined with methotrexate proton pump inhibitors in some patients, there was a slight increase in MTX concentration in blood plasma. In the treatment with high-dose methotrexate should temporarily stop the use of omeprazole.
Formulations which participates in the metabolism of CYP2C19 isozyme
While the use of omeprazole may increase plasma concentrations and increased T 1/2warfarin (R-warfarin), diazepam, phenytoin, cilostazol, imipramine, clomipramine, citalopram, hexobarbital, disulfiram, and other drugs metabolized in the liver with isoenzyme CYP2C19 (may require dose reduction of these drugs). However, omeprazole 20 mg / day did not affect the concentration of phenytoin in the blood plasma in patients receiving long-term phenytoin. When omeprazole patients receiving warfarin and other vitamin K antagonists, requires monitoring INR. At the same time concomitant treatment with omeprazole 20 mg daily dose does not change the time of coagulation in patients receiving long-term warfarin.
Inhibitors isozymes CYP2C19 and / or CYP3A4
The simultaneous use of inhibitors of isozymes CYP2C19 and / or CYP3A4 metabolism slows omeprazole.
When co-administered with omeprazole clarithromycin or erythromycin concentration of omeprazole in blood plasma increases.
The combined use of voriconazole and omeprazole leads to an increase in AUC of omeprazole.
Omeprazole dose adjustment when combined with inhibitors of isozymes CYP2C19 and / or CYP3A4 may be required in patients with severe liver failure in the case of prolonged use of omeprazole. For short joint application of adjustment is required in connection with the good tolerability of high doses of omeprazole.
Inductors isozymes CYP2C19 and CYP3A4
Inductors isozymes CYP2C19 and CYP3A4, such as rifampicin, Hypericum perforatum preparations (Hypericum perforatum), when combined with omeprazole may lead to a decrease in the concentration of omeprazole in blood plasma by accelerating the metabolism of omeprazole.
No effect on the metabolism of
Joint reception of omeprazole with amoxicillin or metronidazole does not affect the concentration of omeprazole in blood plasma.
Not identified clinically significant interactions with omeprazole metoprolol, phenacetin, estradiol, budesonide, diclofenac, naproxen, piroxicam, S-warfarin.
Revealed no effect of omeprazole on antacids, theophylline, caffeine, quinidine, lidocaine, propranolol, ethanol.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children, dry, protected from light at a temperature of no higher than 25 В° C. Shelf life - 3 years.
