Ultop, 10 mg 28 pcs.

Ultop is a proton pump inhibitor.

Pharmacodynamics

Inhibits the enzyme H+-K+-ATPase (proton pump) in the parietal cells of the stomach and thus blocks the final stage of hydrochloric acid synthesis. This leads to a decrease in basal and stimulated secretion, regardless of the nature of the stimulus. After single oral administration, the action of omeprazole occurs within the first hour and lasts for 24 h, the maximum effect is reached after 2 h.

After discontinuation of the drug secretory activity is fully restored after 3-5 days. Basal gastric secretion decreases to 94% after 40 mg of omeprazole. Gastric acidity within 24 hours is reduced by 80-97% with 20 mg omeprazole and by 92-94% with 40 mg. Inhibition of 50% of maximum secretion lasts for 24 h.

Pharmacokinetics

Omeprazole is rapidly absorbed from the GI tract, Cmax in plasma is reached after 0.5-1 h. Bioavailability is 30-40%. Bioavailability is slightly increased in elderly patients and patients with hepatic impairment, and to a large extent in patients with chronic hepatic failure (can reach 100%). Binding to plasma proteins is about 90-95%.

Omeprazole is almost completely metabolized in the liver to form 6 pharmacologically inactive metabolites. It is an inhibitor of the CYP2C19 enzyme system. T1/2 is 0.5-1 hours. Renal excretion is 70-80% and bile excretion is 20-30%. In impaired renal function, excretion of omeprazole decreases in proportion to the decrease in creatinine clearance. In liver dysfunction T1/2 is 2-3 h. Total clearance is 500-600 ml/min.

Indications

Enteric capsules 40 mg

Adults

Peptic ulcer of the stomach and duodenum, including prevention of relapses.
Gastroesophageal reflux disease (GERD), reflux esophagitis, including relapse prevention.
Erosive and ulcerative lesions of the stomach and duodenum associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs).
Erosive and ulcerative lesions of the stomach and duodenum associated with Helicobacter pylori (as part of combination therapy).
Zollinger-Ellison syndrome and other pathological conditions associated with increased gastric secretion.

Children

Gastroesophageal reflux disease in children over 2 years of age.

Duodenal ulcer associated with Helicobacter pylori (as part of combination therapy) in children over 4 years of age.

Enteric capsules 10 mg

Short-term therapy of non-ulcer dyspepsia, which is manifested by stomach pain, nausea, heartburn, belching;
Long-term maintenance therapy to prevent relapses of gastroesophageal reflux disease (GERD) (prevention of heartburn relapses);
Long-term maintenance therapy to prevent relapses of gastric and duodenal ulcers.

Pharmacological effect

Pharmacotherapeutic group:

gastric gland secretion reducer, proton pump inhibitor

CodeATX: A02BC01

Pharmacological properties

Pharmacodynamics

Mechanism of action

Omeprazole is a weak base. Concentrated in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, it is activated and inhibits the proton pump – the enzyme H+, K+-ATPase. The effect of omeprazole on the last stage of the formation of hydrochloric acid in the stomach is dose-dependent and provides highly effective inhibition of basal and stimulated secretion of hydrochloric acid, regardless of the stimulating factor.

Effect on the secretion of gastric juice
Omeprazole, when administered orally daily, provides rapid and effective inhibition of daytime and nighttime hydrochloric acid secretion. The maximum effect is achieved within 4 days of treatment. In patients with duodenal ulcers, omeprazole 20 mg causes a sustained reduction in 24-hour gastric acidity by at least 80%. In this case, a decrease in the average maximum concentration of hydrochloric acid after stimulation with pentagastrin by 70% is achieved within 24 hours.

In patients with duodenal ulcers, omeprazole at a dose of 20 mg, when taken orally daily, maintains an acidity value in the intragastric environment at a pH level > 3, on average, for 17 hours a day.

Inhibition of hydrochloric acid secretion depends on the area under the concentration-time curve (AUC)
omeprazole, and not on the concentration of the drug in the blood plasma at a given time.

Effect on Helicobacter pylori

Omeprazole has a bactericidal effect against Helicobacter pylori in vitro. Eradication of Helicobacter pylori when using omeprazole simultaneously with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of defects in the mucous membrane of the gastrointestinal tract and long-term remission of peptic ulcer disease, which reduces the likelihood of complications such as bleeding, as effective as continuous maintenance therapy.

Other effects associated with inhibition of hydrochloric acid secretion

Patients taking drugs that reduce the secretion of gastric glands for a long period of time are more likely to experience the formation of glandular cysts in the stomach; the cysts are benign and go away on their own with continued therapy. These phenomena are caused by physiological changes resulting from inhibition of hydrochloric acid secretion.

Reducing the secretion of hydrochloric acid in the stomach under the influence of proton pump inhibitors or other agents that reduce gastric acidity leads to an increase in the growth of normal intestinal microflora,
which in turn may lead to a slight increase in the risk of developing intestinal infections caused by bacteria of the genus Salmonella spp. and Campylobacter spp., and in hospitalized patients, probably also Clostridium difficile.

During treatment with drugs that reduce the secretion of gastric glands, the concentration of gastrin in the blood serum increases.

Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A (CgA) in the blood plasma increases.
Increased concentrations of CgA in blood plasma may affect the results of examinations to detect neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors must be suspended 5 days before testing the concentration of CgA in the blood plasma. If after 5 days the concentrations of gastrin and CgA in the blood plasma have not returned to normal values, the study should be repeated 14 days after stopping the use of omeprazole. In children and adult patients taking omeprazole for a long time, an increase in the number of enterochromaffin-like cells was observed, probably associated with an increase in the concentration of gastrin in the blood serum. This phenomenon has no clinical significance.

Pharmacokinetics

Suction and distribution

Omeprazole is absorbed in the small intestine, usually within 3-6 hours. Bioavailability after oral administration is approximately 60%. Food intake does not affect the bioavailability of omeprazole. The binding rate of omeprazole to plasma proteins is about 95%, the volume of distribution is 0.3 l/kg.

Metabolism

Omeprazole is completely metabolized in the liver. The main enzymes involved in the metabolic process are isoenzymes CYP2C19 and CYP3A4. The resulting metabolites – sulfone, sulfide and hydroxyomeprazole do not have a significant effect on the secretion of hydrochloric acid.

The total plasma clearance is 0.3-0.6 l/min. The bioavailability of omeprazole increases by approximately 50% with repeated doses compared to a single dose.

Excretion

The half-life is about 40 minutes (30-90 minutes). About 80% is excreted as metabolites by the kidneys, and the rest through the intestines.

Special 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.

Special instructions

In the presence of any alarming symptoms (for example, such as significant spontaneous weight loss, repeated vomiting, dysphagia, vomiting with blood or melena), as well as in the presence of a gastric ulcer (or if a gastric ulcer is suspected), the presence of a malignant neoplasm should be excluded, since treatment with Ultop® may lead to a smoothing of symptoms and delay the diagnosis.

The simultaneous use of omeprazole with drugs such as atazanavir and nelfinavir is not recommended.

According to the results of the studies, a pharmacokinetic/pharmacodynamic interaction was noted between clopidogrel (loading dose of 300 mg and maintenance dose of 75 mg/day) and omeprazole (80 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel and a decrease in the maximum inhibition of ADP-induced platelet aggregation. Therefore, the simultaneous use of omeprazole and clopidogrel should be avoided (see section “Interaction with other drugs”).

Severe hypomagnesemia, manifested by symptoms such as fatigue, delirium, convulsions, dizziness and ventricular arrhythmia, has been reported in patients receiving omeprazole for at least 3 months. In most patients, hypomagnesemia was relieved after discontinuation of proton pump inhibitors and administration of magnesium supplements. In patients who are planning long-term therapy or who are prescribed omeprazole with digoxin or other drugs that can cause hypomagnesemia (for example, diuretics), plasma magnesium levels should be assessed before initiating therapy and monitored periodically during treatment.

Observational studies suggest that proton pump inhibitors may increase the overall risk of fracture by 10% to 40%. Some degree of this increase may be due to other risk factors.
Patients at risk of developing osteoporosis should be treated according to current clinical guidelines and should consume adequate amounts of vitamin D and calcium. Omeprazole, like all drugs that reduce acidity, can lead to decreased absorption of vitamin B12 (cyanocobalamin). This must be remembered in patients with a reduced supply of vitamin B12 in the body or with risk factors for impaired absorption of vitamin Bp during long-term therapy with omeprazole.

Patients taking drugs that reduce the secretion of gastric glands for a long time are more likely to experience the formation of glandular cysts in the stomach, which go away on their own with continued therapy. These phenomena are caused by physiological changes resulting from inhibition of hydrochloric acid secretion.

Reduced gastric acid secretion by proton pump inhibitors or other acid-inhibiting agents leads to an increase in the growth of normal intestinal microflora, which in turn may lead to a slight increase in the risk of developing intestinal infections caused by Salmonella spp. and Campylobacter spp., as well as possibly Clostridium difficile bacteria in hospitalized patients.

The use of proton pump inhibitors is associated with extremely rare cases of PCLE. In case of pathological changes in the skin, especially in open areas, accompanied by arthralgia, the patient should immediately seek medical help. The doctor should consider discontinuing Ultop®. PCLE due to prior therapy with a proton pump inhibitor may increase the risk of developing PCLE during subsequent therapy with other proton pump inhibitors.

Increased plasma concentrations of chromogranin A (CgA) may interfere with the results of studies performed to diagnose neuroendocrine tumors. To avoid this effect, treatment with Ultop® should be stopped at least 5 days before determining the concentration of CgA (see the “Pharmacodynamics” subsection of the “Pharmacological properties” section) in the blood plasma. If CgA and gastrin concentrations have not returned to normal after the initial measurement, a follow-up study should be performed 14 days after discontinuation of proton pump inhibitor treatment.

The drug Ultop® contains sucrose, therefore it is contraindicated in case of fructose intolerance, sucrase/isomaltase deficiency, glucose-galactose malabsorption syndrome. The hydrosorbent capsule sealed into the bottle cap should not be swallowed!

Effect on the ability to drive a car or other mechanical means

In normal doses, Ultop does not affect the speed of psychomotor reactions and concentration.

Active ingredient

Omeprazole

Composition

1 capsule 10 mg/40 mg contains:

Active substance: Omeprazole 10.00 mg/40.00 mg

Excipients: Granulated sugar (sucrose, starch syrup), hyprolose, magnesium hydroxycarbonate (magnesium carbonate, heavy), sucrose, corn starch, sodium lauryl sulfate, methacrylic acid and ethyl acrylate copolymer (1:1) 30% dispersion, talc, macrogol 6000, titanium dioxide

Composition of empty gelatin capsule

Cap: Gelatin, titanium dioxide (E171), red iron oxide dye (E172)

Body: Gelatin, titanium dioxide (E171), red iron oxide dye (E172)

Pregnancy

Research results indicate no adverse effects on the course of pregnancy, the health of the fetus and newborn child. Omeprazole can be used during pregnancy. Omeprazole is excreted in breast milk. However, when used in therapeutic doses, the effect on a child is unlikely.

Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or any of the components of the drug.
Fructose intolerance, sucrase/isomaltase deficiency, glucose-galactose malabsorption syndrome.
Concomitant use with erlotinib, posaconazole, nelfinavir, St. John’s wort preparations.
Concomitant use with clarithromycin in patients with liver failure.
Children under 2 years of age and weighing <20 kg (for the treatment of reflux esophagitis, symptomatic treatment of heartburn and sour belching, for gastroesophageal reflux disease). Children under 4 years of age (when treating duodenal ulcers caused by Helicobacter pylori).

With caution

Renal and/or liver failure, osteoporosis, pregnancy, simultaneous use with atazanavir (the dose of omeprazole should not exceed 20 mg per day), clopidogrel, warfarin, diazepam, saquinavir, clarithromycin, rifampicin, itraconazole, cilostazol, phenytoin, tacrolimus, voriconazole, the presence of “alarming” symptoms (significant weight loss, repeated vomiting, vomiting with blood, difficulty swallowing, change in the color of stool [tarry stools] and others [see section “Special instructions”]), deficiency of vitamin B12 (cyanocobalamin).

Side Effects

To indicate the frequency of side effects, the classification of the frequency of side effects recommended by the World Health Organization (WHO) was used:

very often > 1/10
often from > 1/100 to < 1/10
uncommon > 1/1000 to < 1/100
rarely from > 1/10000 to < 1/1000
very rare <1/10000
frequency unknown cannot be estimated from available data.

Blood and lymphatic system disorders:

rarely: leukopenia, thrombocytopenia;
very rarely: agranulocytosis, pancytopenia;

Immune system disorders:
rarely: hypersensitivity reactions (for example, fever, angioedema, anaphylactic reaction/anaphylactic shock).

Metabolic and nutritional disorders:
rarely: hyponatremia; frequency unknown: hypomagnesemia, hypocalcemia due to severe hypomagnesemia, hypomagnesemia may be associated with hypokalemia.

Mental disorders:
uncommon: insomnia;
rarely: agitation, confusion, depression;
very rarely: aggression, hallucinations.

Nervous system disorders:
often: headache; uncommon: dizziness, paresthesia, drowsiness;
rarely: taste disturbance.

Visual disturbances: rarely: blurred vision.

Hearing and labyrinthine disorders: uncommon: vertigo.

Disorders of the respiratory system, chest and mediastinal organs: rarely: bronchospasm.

Gastrointestinal disorders:
often: abdominal pain, diarrhea, flatulence, nausea/vomiting, constipation;
rarely: dryness of the oral mucosa, stomatitis, candidiasis of the gastrointestinal tract;

frequency unknown: microscopic colitis.

Liver and biliary tract disorders:
uncommon: increased activity of liver enzymes in the blood plasma; rarely: hepatitis (with or without jaundice); very rare: liver failure, encephalopathy in patients with liver disease.

Skin and subcutaneous tissue disorders:
uncommon: dermatitis, itching, skin rash, urticaria;
rarely: alopecia, photosensitivity;
very rare: erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis;
frequency unknown: subacute cutaneous lupus erythematosus (SCLE).

Musculoskeletal and connective tissue disorders:
uncommon: fracture of the hip, wrist and spine;
rarely: arthralgia, myalgia; very rarely: muscle weakness.

Renal and urinary tract disorders:/p>
rarely: interstitial nephritis.

Disorders of the genital organs and breast:
very rare: gynecomastia.

General disorders and disorders at the injection site:
uncommon: malaise, peripheral edema;
rarely: increased sweating.

Interaction

The effect of omeprazole on the pharmacokinetics of other drugs

A decrease in the secretion of hydrochloric acid in the stomach during treatment with omeprazole and other proton pump inhibitors can lead to a decrease or increase in the absorption of other drugs, the absorption of which depends on the acidity of the environment.

Like other drugs that reduce gastric acidity, treatment with omeprazole may result in decreased absorption of posaconazole, erlotinib, ketoconazole and itraconazole, and increased absorption of drugs such as digoxin.

Simultaneous administration of omeprazole at a dose of 20 mg 1 time per day and digoxin increases the bioavailability of digoxin by 10% (the bioavailability of digoxin increased by up to 30% in 20% of patients).

Omeprazole has been shown to interact with some antiretroviral drugs.

The mechanisms and clinical significance of these interactions are not always known. An increase in pH during omeprazole therapy may affect the absorption of antiretroviral drugs. Interaction at the level of the CYP2C19 isoenzyme is also possible. With the simultaneous use of omeprazole and some antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their concentration in the blood serum is observed during omeprazole therapy. In this regard, the simultaneous use of omeprazole with antiretroviral drugs such as atazanavir and nelfinavir is not recommended. With the simultaneous use of omeprazole and saquinavir, an increase in the concentration of saquinavir in the blood serum was noted; when used with some other antiretroviral drugs, their concentration did not change.

Omeprazole inhibits the CYP2C19 isoenzyme, the main isoenzyme involved in its metabolism.
Concomitant use of omeprazole with other drugs metabolized by the CYP2C19 isoenzyme, such as diazepam, warfarin (R-warfarin) or other vitamin K antagonists, phenytoin and cilostazol, may lead to a slower metabolism of these drugs. Monitoring of patients taking phenytoin and omeprazole is recommended; a dose reduction of phenytoin may be required. However, simultaneous treatment with omeprazole at a daily dose of 20 mg does not affect the concentration of phenytoin in the blood plasma in patients taking the drug for a long time.

When using omeprazole in patients receiving warfarin or other vitamin K antagonists, monitoring of the international normalized ratio (INR) is necessary; in some cases, it may be necessary to reduce the dose of warfarin or another vitamin K antagonist. At the same time, simultaneous treatment with omeprazole at a daily dose of 20 mg does not lead to a change in coagulation time in patients taking warfarin for a long time.

The use of omeprazole at a dose of 40 mg 1 time per day leads to an increase in the maximum concentration (Cmax) and AUC in the blood plasma for cilostazol and one of its active metabolites.

A pharmacokinetic/pharmacodynamic interaction has been noted between clopidogrel (loading dose 300 mg and maintenance dose 75 mg/day) and omeprazole (80 mg/day orally), which leads to a decrease in exposure to the active metabolite of clopidogrel and a decrease in the maximum inhibition of ADP-induced platelet aggregation.

The clinical significance of this interaction is unclear. There is no proven increase in the risk of cardiovascular complications with simultaneous use of clopidogrel, acetylsalicylic acid (ASA) and proton pump inhibitors, including omeprazole at a dose of 20 mg/day. The results of a number of observational studies are contradictory and do not provide a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications during the simultaneous use of clopidogrel and proton pump inhibitors. When clopidogrel was administered concomitantly with a fixed combination of 20 mg esomeprazole and 81 mg ASA, exposure to the active metabolite of clopidogrel was reduced by almost 40% compared with clopidogrel monotherapy, while the maximum levels of inhibition of ADP-induced platelet aggregation were similar, which is likely due to the concomitant use of low dose ASA.

Overdose

Patients tolerate daily doses of up to 360 mg well.

Symptoms: abdominal pain, drowsiness, headache, dizziness, dry mouth, tachycardia, arrhythmia, blurred vision, agitation, confusion, increased sweating, nausea; in rare cases: convulsions, shortness of breath, hypothermia.

Treatment is symptomatic. There is no specific antidote. Hemodialysis is not enough
effective.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children

Shelf life

3 years

Do not use after expiration date.

Manufacturer

KRKA-RUS, Russia