Composition, form of production and packaging
Powder for the preparation of a suspension for oral administration from white to almost white, with the smell of mint; the prepared suspension is from white to almost white.
1 pack.
omeprazole 20 mg
Excipients: sodium hydrogen carbonate - 1680 mg, xylitol - 2000 mg, sucrose - 2070 mg, sucralose - 30 mg, xanthan gum - 55 mg, flavoring mint - 30 mg.
5.885 g - sachets of the combined material (5) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
Antiulcer drug.
Mechanism of action
Omeprazole is a weak base. Concentrates in the acidic environment of the secretory tubules of the 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 ulcer, omeprazole at a dose of 20 mg causes a steady decrease in gastric acidity by at least 80% for 24 hours. At the same time, the mean C max of hydrochloric acid is reduced after pentagastrin stimulation by 70% for 24 hours.
In patients with duodenal ulcer, the daily oral administration of omeprazole at a dose of 20 mg maintains the value of intragastric acidity at pH> 3 for 17 hours.
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
Omeprazole in vitro has a bactericidal effect on 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 prolonged 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 for a long period of time drugs that reduce the secretion of the glands of the stomach, 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.
The decrease in the secretion of hydrochloric acid in the stomach results in a slight increase in the risk of intestinal infections caused by Salmonella spp., Campylobacter 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
Absorption is high; Time to reach C max , on average - 30 min (10-90 min), bioavailability - 30-40%. 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 CYP2C19 and CYP3A4 with the formation of inactive metabolites of sulfone, sulfide and hydroxyomeprazole. Omeprazole, not included by parietal cells in the formation of active metabolites, is completely metabolized in the liver also with the participation of CYP2C19 and CYP3A4 isoenzymes.
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 in the form of metabolites with urine, the rest - with feces.
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 (with liver failure increases to almost 100%) and a significant decrease in plasma clearance.
INDICATIONS
Adults
- heartburn and other symptoms associated with gastroesophageal reflux disease (GERD);
- non-erosive and erosive (reflux-esophagitis) forms of GERD;
- Stomach ulcer and duodenal ulcer (including the prevention of relapses);
- 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;
- hypersecretory states (Zollinger-Ellison syndrome, stress ulcers of the gastrointestinal tract, polyendocrine adenomatosis, systemic mastocytosis).
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.
Safety and efficacy in other indications in pediatric patients is not established.
DOSING MODE
The drug is taken orally. Pour the contents of the sachet into a cup, add 1-2 tablespoons of water (do not use other liquids or food products), stir thoroughly until a homogeneous suspension is obtained and immediately drink. If necessary, you can drink a small amount of water.
To ensure the following dosing regimens, the drug can be taken at another registered dosage (Omez В® , capsules 10 mg, 20 mg and 40 mg; Omega В® Insta, powder for oral suspension, 20 mg; Omega В® , lyophilizate for solution for infusion , 40 mg).
Adults
With heartburn and other symptoms associated with gastroesophageal reflux disease (GERD), a single dose of 20 mg of the drug is sufficient for rapid relief of symptoms.
With non-erosive and erosive (reflux-esophagitis) forms of GERD , depending on the severity of esophagitis - from 20 mg to 80 mg per day. The daily dose can be divided into 2-3 doses.
The duration of the basic course is 4-8 weeks. After healing of erosion, supportive treatment is shown for 26-52 weeks, with severe esophagitis - for life. Forprevention of exacerbation of reflux esophagitis - 20 mg / day.
With peptic ulcer of the stomach and duodenal ulcer (including the prevention of recurrence) appoint 20 mg 1 time / day. Patients resistant to treatment with other antiulcer drugs - 40 mg / day. The course of treatment for duodenal ulcer - 2 weeks, if necessary - up to 4 weeks, with peptic ulcer of the stomach - 4-8 weeks.
To eradicate Helicobacter pylori in infected patients with peptic ulcer of the stomach and duodenum , as well as other diseases requiring eradication (as part of a combination therapy), according to the recommendations of the Maestricht-4 working group, Omez В® Insta can be included in the following treatment regimens :
- the first line (the standard triple scheme): Omez В® Insta 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 prescribe Omez В® Insta 40 mg (2 bags of 20 mg) 2 times / day (doubling the standard dose) and increasing the course duration from 7 to 10-14 days;
- the second line (four-component): it is used for ineffectiveness of standard triple therapy or for intolerance to antibiotics of the penicillin group. Bismuth titrate dicitrate (120 mg 4 times / day) in combination with Omez В® Insta (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 antibiotics.
For the prevention and treatment of gastric and duodenal ulcer damage caused by NSAID (NSAID-gastropathy), such as dyspepsia, mucosal erosion, peptic ulcer, Omez В® Insta is prescribed at a dose of 20 mg daily before breakfast for the entire course of the course treatment of NSAIDs; for the purpose of treatment - in a dose of 20 mg 2 times or once 40 mg (2 bags of 20 mg) per day for 4-8 weeks.
At hypersecretory conditions (Zollinger-Ellison syndrome, stress ulcers of the gastrointestinal tract, polyendocrine adenomatosis, systemic mastocytosis) - 60 mg / day; if necessary, increase the dose to 80-120 mg / day (in this case, it is prescribed in 2-3 sessions).
Children
For gastroesophageal reflux disease, children over 2 years of age, with a body weight of more than 20 kg, are recommended to prescribe Omez В® Insta in a dose of 20 mg 1 time / day. The duration of treatment is 4-8 weeks;
With duodenal ulcer caused by Helicobacter pylori, children over the age of 4, 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.
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 per day.
The rate of metabolism of omeprazole in elderly patients is reduced, but dose adjustment is not required.
SIDE EFFECT
The incidence of unwanted drug reactions is described 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 and nutrition: 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 concomitant use with clarithromycin (a consequence of inhibiting the secretion of hydrochloric acid, is benign, reversible).
From the liver and biliary tract: infrequently - increased activity of liver 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, erythema multiforme exudative, 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
- hypersensitivity to omeprazole, substituted benzimidazoles or other components of the drug;
- fructose intolerance, sugarase / isomaltase deficiency, glucose-galactose malabsorption (due to the presence of sucrose in the formulation).
- simultaneous use with atazanavir, nelfinavir, erlotinib, posaconazole;
- the use of omeprazole in children, except as indicated by gastroesophageal reflux disease for children over 2 years old, with a body weight of more than 20 kg and duodenal ulcer caused by Helicobacter pylori, for children over 4 years of age, with a body weight of more than 20 kg.
With caution should prescribe the drug for renal failure (correction of the dose of omeprazole is not required) and liver failure.
PREGNANCY AND LACTATION
The results of the studies showed no side effects of omeprazole on the health of pregnant women, on the fetus or on the 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
With caution should prescribe the drug for kidney failure (correction of the dose of omeprazole is not required).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
With caution should prescribe the drug for liver failure.
APPLICATION FOR CHILDREN
Contraindicated the use of omeprazole in children, except for indications for gastroesophageal reflux disease for children over 2 years old, with a body weight of more than 20 kg and duodenal ulcer caused by Helicobacter pylori, for children over 4 years old, with a body weight of more than 20 kg.
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 with a stomach ulcer (or suspected gastric ulcer), the possibility of malignant growth should be excluded, since omeprazole therapy may result to smoothing the symptoms and delaying 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.
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 severe hypomagnesemia in patients receiving therapy for more than one year with proton pump inhibitors, including omeprazole.
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.
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, there is a decrease in the antiplatelet effect of the latter.
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: headache, dizziness, confusion, confusion, tachycardia, arrhythmia, blurred vision, drowsiness, dry mouth, nausea, vomiting, flatulence.
Treatment: symptomatic. If necessary - gastric lavage, activated charcoal. Hemodialysis is not effective enough.
DRUG INTERACTION
Substances with pH-dependent absorption
Like other drugs that reduce the acidity of gastric juice, treatment with omeprazole may lead to a decrease in absorption of ketoconazole, itraconazole, posaconazole, erlotinib, iron preparations and cyanocobalamin. They should be avoided together with omeprazole.
Digoxin
The bioavailability of digoxin when used concomitantly with omeprazole is increased by 10% (correction of the digoxin dosage regimen may be required). Care should be taken when using these drugs at the same time in elderly patients.
Clopidogrel
Based on the results of the studies, the interaction between clopidogrel (loading dose 300 mg, maintaining a dose of 75 mg / day) and omeprazole (80 mg / day inwards) is noted, which reduces the exposure of the active metabolite clopidogrel and reduces the inhibition of platelet aggregation. Probably, the observed effect is due to the inhibitory effect of omeprazole on the isoenzyme CYP2C19. Therefore, simultaneous use of omeprazole and clopidogrel should be avoided.
Antiretroviral drugs
An increase in pH on the background of omeprazole therapy may affect the absorption of antiretroviral drugs. It is also possible to interact at the level of the isoenzyme CYP2C19. 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 of methotrexate in high doses should temporarily stop taking 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.
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 dose 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 at a temperature of no higher than 25 В° C. Shelf life - 2 years.
