Gastrozol 10 mg 28 pcs. enteric capsules

pharmachologic effect

Antiulcer drug, inhibitor of H+-K+-ATPase (proton pump). Omeprazole reduces acid production - inhibits the activity of H+-K+-ATPase in the parietal cells of the stomach and thereby blocks the final stage of hydrochloric acid synthesis. The drug is a prodrug and is activated in the acidic environment of the secretory tubules of parietal cells. Reduces the level of basal and stimulated secretion, regardless of the nature of the stimulus. After taking the drug orally at a dose of 20 mg, the antisecretory effect develops within the first hour, maximum after 2 hours. Inhibition of 50% of maximum secretion continues for 24 hours. Taking the drug 1 time per day provides rapid and effective inhibition of day and night gastric secretion, reaching its maximum after 4 days of treatment and disappearing by the end of 3-4 days after stopping the drug. In patients with duodenal ulcer, taking the drug at a dose of 20 mg maintains the intragastric acidity level (pH) at level 3 for 17 hours.

Side effect

From the digestive system: - diarrhea or constipation, abdominal pain, nausea, vomiting, flatulence; - rarely - increased activity of liver transaminases, taste disturbances, formation of gastric glandular cysts during long-term treatment (a consequence of inhibition of gastric hydrochloric acid secretion, is benign, reversible); - in some cases - dry mouth, stomatitis; in patients with previous severe liver disease - hepatitis (including jaundice), impaired liver function. From the hematopoietic system: in some cases - leukopenia, thrombocytopenia, agranulocytosis, pancytopenia. From the central nervous system and peripheral nervous system: - in patients with severe concomitant somatic diseases - dizziness, headache, agitation, depression; - in patients with previous severe liver disease - encephalopathy. From the musculoskeletal system: in some cases - arthralgia, myasthenia, myalgia. Dermatological reactions: - rarely - skin rash and/or itching; - in some cases - photosensitivity, exudative erythema multiforme, alopecia. Allergic reactions: urticaria, angioedema, fever, bronchospasm, interstitial nephritis, anaphylactic shock. Other: rarely - gynecomastia, malaise, blurred vision, peripheral edema, increased sweating.

Gastrozol 10 mg 28 pcs. enteric capsules

pharmachologic effect

A drug that reduces the secretion of gastric glands - a proton pump inhibitor.

Composition and release form Gastrozol 10 mg 28 pcs. enteric capsules

Capsules - 1 kps.:

• active ingredient: omeprazole - 10.0 mg;
• excipients: mannitol - 19.97 mg, sucrose - 32.11 mg, disodium hydrogen phosphate - 1.49 mg, sodium lauryl sulfate - 0.40 mg, lactose monohydrate - 4.00 mg, calcium carbonate - 4.00 mg, hypromellose (hydroxypropyl methylcellulose E-5) - 10.28 mg, methacrylic acid and ethyl acrylate copolymer [1:1 ](L-30D) - 29.37 mg, propylene glycol - 0.95 mg, diethyl phthalate - 2.94 mg, cetyl alcohol - 0.88 mg, sodium hydroxide - 0.18 mg, polysorbate-80 - 0.35 mg, povidone (polyvinylpyrrolidone, povidone K-30) - 0.30 mg, titanium dioxide - 0.21, talc - 0.07 mg ;
• capsule shell body: titanium dioxide (E 171) - 2.0000%, gelatin - up to 100%;
• capsule shell cap: titanium dioxide (E171) - 1.3333%, sunset yellow dye (E 110) - 0.0044%, quinoline yellow (E 104) - 0.9197%, gelatin - up to 100%.

7 or 10 capsules in a blister pack made of polyvinyl chloride film or PA/Al/PVC film and aluminum foil.

1,2, 3 or 4 blister packs together with instructions for use are placed in a cardboard pack.

Description of the dosage form

Opaque capsules No. 2. The body is white, the cap is yellow. The contents of the capsules are white to almost white pellets.

Directions for use and doses

Orally, with a sufficient amount of water (the contents of the capsule must not be chewed), 30 minutes before meals. If the patient is unable to swallow the capsule whole, its contents can be dissolved in a small amount of water or fruit juice (do not dissolve in carbonated drinks). The resulting drug solution should be drunk immediately after preparation with an additional 1/2 glass of water.

Symptoms of gastroesophageal reflux such as heartburn, sour belching.

The usual dose of Gastrozol® is 10 mg (1 capsule) once a day. The maximum daily dose of the drug should not exceed 20 mg. The lowest effective dose should always be used. The maximum course of treatment without consulting a doctor is 14 days. The interval between 14-day courses of treatment should be at least 4 months.

If symptoms do not improve within 2 weeks or if they worsen, you should consult your doctor!

Use of the drug in special cases

The possibility of using the drug Gastrozol® in special cases is assessed by a doctor.

Renal dysfunction.

No dose adjustment is required.

Liver dysfunction.

In patients with impaired liver function, the bioavailability and clearance of omeprazole is increased. Before use, you should consult your doctor.

Elderly age.

Despite the fact that the rate of metabolism of omeprazole in elderly people decreases, dose adjustment is not required when using the drug in a daily dose of 20 mg or less.

Pharmacodynamics

Omeprazole inhibits the enzyme H+K+-ATPase (“proton pump”) in the parietal cells of the stomach, thereby blocking the final stage of hydrochloric acid secretion. This leads to a decrease in the level of basal and stimulated acid secretion, regardless of the nature of the stimulus. After a single oral dose, the effect of omeprazole occurs within the first hour and continues for 24 hours. The maximum effect is achieved after 2 hours. After stopping the drug, secretory activity is completely restored after 3 to 5 days.

Pharmacokinetics

Suction

After oral administration, omeprazole is rapidly absorbed from the gastrointestinal tract, the maximum concentration (Cmax) of omeprazole in the blood plasma is reached after 0.5 - 3.5 hours. Bioavailability is 30 - 40%.

Distribution

Binding to blood plasma proteins is about 95%.

Metabolism

Omeprazole is almost completely metabolized in the liver with the participation of the CYP2C19 isoenzyme with the formation of six pharmacologically inactive metabolites.

Removal

The half-life (T1/2) is 0 5-1 hour. Excreted in the form of metabolites by the kidneys (70 - 80%) and with bile (20 - 30%).

Pharmacokinetics in special clinical situations

In patients with hepatic impairment, bioavailability increases significantly and the half-life increases to 3 hours. In elderly patients, the rate of elimination decreases, bioavailability increases.

Indications for use Gastrozol 10 mg 28 pcs. enteric capsules

Symptoms of gastroesophageal reflux such as heartburn, sour belching.

Contraindications

Hypersensitivity to omeprazole, substituted benzimidazoles or other components of the drug.

Concomitant use with nelfinavir, atazanavir, erlotinib, posaconazole.

Age up to 18 years.

Carefully:

Before using the drug, you should consult your doctor in the following cases:

• in the presence of previously diagnosed gastric ulcer; severe liver disease accompanied by liver failure; jaundice; previous surgical intervention on the gastrointestinal tract;
• in the presence of “alarming” symptoms: significant spontaneous weight loss, repeated vomiting, vomiting with blood, changes in the color of stool (tarry stools - melena), difficulty swallowing;
• when new symptoms appear or changes in existing symptoms from the gastrointestinal tract;
• in the presence of osteoporosis;
• against the background of ongoing symptomatic treatment for indigestion or persistent heartburn (for 4 weeks or more);
• when used simultaneously with one or more of the following drugs: clopidogrel, digoxin, erlotinib, ketoconazole, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, clarithromycin, voriconazole, rifampicin, St. John's wort preparations.

It is also recommended to consult a doctor before using Gastrozol® during pregnancy and breastfeeding.

Application Gastrozol 10 mg 28 pcs. enteric capsules during pregnancy and breastfeeding

The results of three prospective epidemiological studies (more than 1000 observations) showed that the use of omeprazole in pregnant women does not have a negative effect on the course of pregnancy and the health of the fetus/newborn. However, before using the drug during pregnancy, it is recommended to consult a doctor.

Omeprazole passes into breast milk. If it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

special instructions

Omeprazole is not intended for use in cases of occasional heartburn (heartburn less than 2 times a week).

Before starting therapy with omeprazole, it is necessary to exclude the presence of a malignant process in the upper gastrointestinal tract, since taking omeprazole can mask symptoms and delay the correct diagnosis.

A 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 developing intestinal infections caused by bacteria of the genus Salmonella spp., Campylobacter spp., as well as Clostridium difficile bacteria. A decrease in hydrochloric acid secretion may lead to an increase in chromogranin A (CgA) concentrations, which affects the results of examinations for the detection of neuroendocrine tumors, therefore, to prevent this effect, it is necessary to temporarily stop taking omeprazole 5 days before the CgA concentration test. If during this time the CgA concentration has not returned to normal, the study should be repeated.

The risk-benefit ratio of long-term (more than 1 year) omeprazole maintenance therapy should be regularly assessed. There is evidence of an increased risk of fractures of the vertebrae, wrist bones, and head of the femur, mainly in elderly patients or in the presence of other risk factors. Patients at risk of developing osteoporosis should ensure adequate intake of vitamin D and calcium.

Severe hypomagnesemia, manifested by symptoms such as fatigue, delirium, seizures, dizziness and ventricular arrhythmia, has been reported in patients receiving omeprazole for at least three months. In most patients, hypomagnesemia was relieved after discontinuation of proton pump inhibitors and administration of magnesium supplements. Patients receiving omeprazole therapy for a long time, especially in combination with digoxin or other drugs that reduce magnesium levels in the blood plasma (diuretics), require regular monitoring of magnesium levels.

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 during long-term therapy.

In patients taking drugs orally for a long time that reduce the secretion of gastric glands, the formation of glandular cysts in the stomach was more often observed. These phenomena are caused by physiological changes as a result of inhibition of hydrochloric acid secretion, and undergo reverse development as therapy continues.

Impact on the ability to drive vehicles and operate machinery

During treatment with omeprazole, dizziness, confusion, drowsiness, and blurred vision may occur, so care should be taken when driving a vehicle or operating other mechanisms and performing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Overdose

Symptoms: dizziness, confusion, apathy, depression, drowsiness, headache, blurred vision, vascular dilation, tachycardia, nausea, vomiting, flatulence, abdominal pain, diarrhea, increased sweating, dry mouth.

Treatment: symptomatic. If necessary, gastric lavage and administration of activated carbon. Hemodialysis is not effective enough.

Side effects Gastrozol 10 mg 28 pcs. enteric capsules

The frequency of side effects is presented in accordance with the following gradation: very often (≥ 1/10); often (≥ 1/100,

Allergic reactions: uncommon - urticaria, skin rash, itching; rarely - fever, urticaria, angioedema, anaphylactoid reactions; very rarely - eosinophilia.

From the gastrointestinal tract: often - nausea, vomiting, abdominal pain, diarrhea or constipation, flatulence; infrequently - increased activity of liver enzymes (transaminases) and alkaline phosphatase (reversible), taste distortion (usually resolves after cessation of therapy); rarely - dry mouth, stomatitis, candidiasis of the gastrointestinal tract, hepatitis (with or without jaundice), microscopic colitis, discoloration of the tongue to brown-black and the appearance of benign cysts of the salivary glands when used simultaneously with clarithromycin (the phenomena are reversible after discontinuation therapy); very rarely - liver failure (in patients with previous severe liver disease).

From the nervous system: often - headache; infrequently - dizziness, paresthesia, drowsiness, insomnia; rarely - agitation, reversible confusion, depression; very rarely - aggression, confusion, hallucinations; against the background of severe liver disease - encephalopathy.

From the skin and subcutaneous tissues: infrequently - dermatitis; rarely - photosensitivity (redness of the skin), alopecia; very rarely - exudative erythema multiforme, Stevens-Johnson syndrome (severe erythema multiforme, characterized by the appearance of spots and blisters on the skin and mucous membranes against the background of high fever and joint pain), toxic epidermal necrolysis; frequency unknown - subacute cutaneous lupus erythematosus.

On the part of the organ of vision: infrequently - visual disturbances, including a decrease in visual fields, a decrease in the acuity and clarity of visual perception (usually disappear after cessation of therapy).

From the organ of hearing and labyrinthine disorders: infrequently - disorders of auditory perception, including “ringing in the ears” (usually disappear after cessation of therapy), vertigo.

From the musculoskeletal and connective tissue side: infrequently - fractures of the vertebrae, wrist bones, femoral head; rarely - myalgia (muscle pain), arthralgia (joint pain), muscle weakness.

From the respiratory system: rarely - bronchospasm.

From the kidneys and urinary tract: rarely - interstitial nephritis.

From the hematopoietic organs: rarely - leukopenia, thrombocytopenia; very rarely - agranulocytosis, pancytopenia.

From the endocrine system: very rarely - gynecomastia.

Other: infrequently - peripheral edema, malaise; rarely - increased sweating, hyponatremia; very rarely - hypomagnesemia, hypocalcemia due to severe hypomagnesemia.

Cases of the formation of glandular cysts in the stomach have been reported in patients taking drugs that reduce the secretion of gastric glands for a long period of time; The cysts are benign and go away on their own with continued therapy.

If side effects not listed in these instructions occur, you should immediately consult a doctor.

Drug interactions

You should consult your doctor before taking Gastrozol® if you are being treated with one or more of the drugs listed in this section.

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 lead to decreased absorption of ketoconazole, itraconazole, posaconazole, erlotinib, iron supplements and cyanocobalamin. Their co-administration with omeprazole should be avoided.

The bioavailability of digoxin when used simultaneously with omeprazole increases by 10% (adjustment of the digoxin dosage regimen may be required). Caution should be exercised when these drugs are used concomitantly in elderly 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. When omeprazole is co-administered with certain antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their serum concentrations is observed during omeprazole therapy. When used simultaneously with omeprazole, the area under the concentration-time curve of atazanavir decreases by 75%. In this regard, the combined use of omeprazole with antiretroviral drugs such as atazanavir and nelfinavir is contraindicated. When used concomitantly with omeprazole, an increase in plasma concentrations of saquinavir/ritonavir is observed by up to 70%, while the tolerability of treatment in patients with HIV infection does not deteriorate.

With simultaneous use of omeprazole with clopidogrel, a decrease in the antiplatelet effect of the latter is observed.

When used simultaneously with omeprazole, it is possible to increase the plasma concentration and increase the half-life of warfarin, diazepam, phenytoin, cilostazol, imipramine, clomipramine, citalopram, hexobarbital, disulfiram, as well as other drugs metabolized in the liver with the participation of the CYP2C19 isoenzyme (a dose reduction of these drugs may be required ).

With simultaneous use of omeprazole and tacrolimus, an increase in the concentration of tacrolimus in the blood serum was noted, which may require dose adjustment. In some patients, an increase in methotrexate concentrations was observed during combined use with proton pump inhibitors. When prescribing high doses of methotrexate, the possibility of temporary withdrawal of omeprazole should be considered.

Concomitant use with inhibitors of the CYP2C19 and CYP3A4 isoenzymes (such as clarithromycin and voriconazole) may lead to an increase in the plasma concentration of omeprazole, which may require dose adjustment of omeprazole in patients with severe liver failure, in case of long-term use.

Inducers of the CYP2C19 and CYP3A4 isoenzymes (for example, rifampicin, preparations of St. John's wort (Hypericum perforatum), when used together with omeprazole, can accelerate its metabolism, thereby reducing the concentration of omeprazole in the blood plasma.

No clinically significant interaction of omeprazole with antacids, caffeine, propranolol, theophylline, metoprolol, lidocaine, quinidine, erythromycin, phenacetin, estradiol, amoxicillin, budesonide, diclofenac, metronidazole, naproxen, piroxicam has been established.

Mode of application

The drug is taken orally, usually in the morning, the capsules are not chewed and washed down with a small amount of water (immediately before or during meals). For duodenal ulcer in the acute phase, the drug is prescribed at a dose of 20 mg/day for 2-4 weeks; if the effectiveness is insufficient, the dose can be increased to 40 mg/day. For gastric ulcers in the acute phase and erosive-ulcerative esophagitis - 20-40 mg/day for 4-8 weeks. For erosive and ulcerative lesions of the gastrointestinal tract caused by taking NSAIDs - 20 mg/day for 4-8 weeks. For the purpose of eradication of Helicobacter pylori, 20 mg is prescribed 2 times a day for 7 days in combination with antibacterial agents. To prevent relapses of gastric and duodenal ulcers - 20 mg/day. To prevent relapses of reflux esophagitis - 20 mg/day for a long time (up to 6 months). For Zollinger-Ellison syndrome, the dose is set individually depending on the initial level of gastric secretion, usually starting from 60 mg/day. If necessary, the dose is increased to 80-120 mg/day, in which case it is divided into 2 doses.

Gastrozol®

The drug is taken orally, the capsules are not chewed, usually in the morning with a small amount of water (immediately before or during meals).

For patients with difficulty swallowing and for children who cannot swallow the capsule

Open the capsule and swallow the contents with 100 ml of warm water, or mix the contents of the capsule with an acidic liquid, such as apple juice or still water. Patients should be advised that the resulting dispersion solution should be taken immediately (within 30 minutes) and stirred immediately before use.

Adults

Duodenal ulcer

Patients with an active duodenal ulcer are recommended to take omeprazole 1 capsule (20 mg) once a day.

The drug provides rapid relief of symptoms. In most patients, ulcer healing occurs within 2 weeks. In cases where complete healing of the ulcer does not occur within 2 weeks, healing is achieved with a subsequent 2-week intake of the drug.

Patients with duodenal ulcers that are poorly responsive to treatment are usually prescribed omeprazole 40 mg (2 capsules) once a day; Ulcer healing usually occurs within 4 weeks.

To prevent relapses, patients with duodenal ulcers are recommended to take omeprazole 20 mg once a day. If necessary, the dose can be increased to 40 mg (2 capsules) 1 time per day.

Stomach ulcer

The recommended dose of omeprazole is 20 mg once a day.

The drug provides rapid relief of symptoms. In most patients, cure occurs within 4 weeks. In cases where healing does not occur after the first course of taking the drug, a repeat 4-week course is usually prescribed, during which healing is achieved.

Patients with stomach ulcers that are poorly responsive to treatment are usually prescribed omeprazole 40 mg (2 capsules) once a day; healing is usually achieved within 8 weeks.

To prevent relapses, a dose of 20 mg once daily is recommended for patients with gastric ulcers. If necessary, the dose can be increased to 40 mg 1 time per day.

NSAID-associated gastric ulcers or duodenal erosions

In the presence of NSAID-associated gastric, duodenal ulcers or gastroduodenal erosions in patients with discontinued or ongoing NSAID therapy, the recommended dose of omeprazole is 20 mg once daily.

The drug provides rapid relief of symptoms; in most patients, cure occurs within 4 weeks. In those patients who do not heal during the initial therapy period, healing is usually achieved with a 4-week repeat dosing.

For duodenal ulcers, erosions and symptoms of dyspepsia associated with taking NSAIDs, the recommended dose of the drug is 20 mg once a day.

Helicobacter pylori eradication regimens for peptic ulcer disease

Three-component treatment regimen:

- omeprazole 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg 2 times a day in the morning and evening for 7 days;

- omeprazole 20 mg + metronidazole 400 mg (or tinidazole 500 mg) + clarithromycin 250 mg 2 times a day in the morning and evening for 7 days;

— omeprazole 40 mg (2 capsules) once a day + amoxicillin 500 mg 3 times a day + metronidazole 400 mg 3 times a day for 7 days.

Two-component treatment regimen:

- omeprazole 40-80 mg (2-4 capsules) + amoxicillin 1.5 g daily (the dose should be divided into parts) for 2 weeks.

To ensure complete healing, further treatment should be carried out in accordance with the recommendations in the sections “Duodenal Ulcer” and “Gastric Ulcer”.

In cases where, after completing a course of treatment, a test for Helicobacter pylori

remains positive, the course of treatment can be repeated.

Reflux esophagitis

The recommended dose of omeprazole is 20 mg once a day.

The drug provides rapid relief of symptoms; in most patients, cure occurs within 4 weeks. In cases where, after the first course of taking the drug, complete cure does not occur, a repeated 4-week course of treatment is usually prescribed, during which a cure is achieved.

For patients with severe reflux esophagitis, omeprazole 40 mg (2 capsules) 1 time per day is recommended; cure usually occurs within 8 weeks.

Patients with reflux esophagitis in remission are prescribed omeprazole 20 mg once a day as long-term courses of maintenance therapy. If necessary, the dose can be increased to 40 mg.

Symptomatic gastroesophageal reflux disease

The recommended dose of omeprazole is 20 mg once a day.

The drug provides rapid relief of symptoms. If after 4 weeks of treatment (20 mg 1 time per day) symptoms do not disappear, additional examination of the patient is recommended.

Dyspepsia associated with hyperacidity

To relieve pain and/or eliminate discomfort in the epigastric region, with or without heartburn, omeprazole is prescribed - 20 mg 1 time per day.

If after 4 weeks of treatment symptoms do not disappear, additional examination of the patient is recommended.

Zollinger-Ellison syndrome

For patients with Zollinger-Ellison syndrome, the drug is prescribed in an individual dosage. Treatment is continued according to clinical indications for as long as necessary.

The recommended starting dose of the drug is 60 mg (3 capsules) daily.

In all patients with severe forms of the disease, as well as in cases where other therapeutic methods did not lead to the desired result, the use of the drug was effective in more than 90% of patients when taking 20-120 mg of the drug daily.

In cases where the daily dose of the drug exceeds 80 mg (4 capsules), the dose should be divided into two parts and taken 2 capsules 2 times a day.

Renal dysfunction

In patients with impaired renal function, no dose adjustment is required.

Liver dysfunction

In patients with impaired liver function, the bioavailability and plasma half-life of omeprazole are increased. In this regard, a dose of 20 mg per day is sufficient.

Elderly patients (aged > 65 years)

In elderly people, no dose adjustment is required.

Children

Gastroesophageal reflux disease (GERD) in children over 2 years of age (body weight more than 20 kg)

20 mg 1 time per day.

If necessary, the dose can be increased to 40 mg (2 capsules) 1 time per day.

The duration of treatment for reflux esophagitis is 4-8 weeks.

The duration of treatment for the symptomatic treatment of heartburn and sour belching with GERD is 2-4 weeks.

If the symptoms of the disease do not disappear after using omeprazole for 2-4 weeks, further examination is recommended.

Duodenal ulcer associated with Helicobacter pylori (as part of combination therapy) in children over 4 years of age (body weight more than 31 kg)

For the purpose of eradication of Helicobacter pylori

in children over 4 years of age with duodenal ulcer, combination therapy is carried out taking into account national and regional recommendations regarding bacterial resistance (using appropriate antibacterial agents).

Omeprazole is prescribed 20 mg 2 times a day.

Duration of treatment is 7-14 days.

Interaction

Gastrozole may reduce the absorption of ampicillin esters, iron salts, itraconazole and ketoconazole, because Omeprazole increases the pH of the stomach. As an inhibitor of isoenzymes of the cytochrome P450 system, omeprazole can increase plasma concentrations and reduce the excretion of diazepam, indirect anticoagulants, phenytoin (drugs metabolized in the liver with the participation of CYP2C19), which in some cases may require a reduction in the doses of these drugs. With long-term use of omeprazole at a dose of 20 mg 1 time / day in combination with caffeine, theophylline, piroxicam, diclofenac, naproxen, metoprolol, propranol, ethanolol, cyclosporine, quinidine and estradiol did not lead to a change in their plasma concentrations. Gastrozole enhances the inhibitory effect of other drugs on the hematopoietic system. There was no interaction between omeprazole and concomitantly taken antacids.

GASTROZOL

Interaction

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. When omeprazole is co-administered with certain antiretroviral drugs, such as atazanavir and nelfinavir, a decrease in their serum concentrations is observed during omeprazole therapy. In this regard, the combined 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 serum was noted; when used with some other antiretroviral drugs, their concentration did not change.

Omeprazole inhibits CYP2C19, 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 cilostozol, 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, concomitant 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 is necessary; in some cases, it may be necessary to reduce the dose of warfarin or another vitamin K antagonist. At the same time, concomitant 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 once daily led to an increase in Cmax and AUC of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol, the increase was 29% and 69%, respectively.

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 by an average of 46% and decrease in maximum inhibition of ADP-

induced platelet aggregation by an average of 16%.

The clinical significance of this interaction is unclear. An increased risk of cardiovascular complications with concomitant use of clopidogrel and proton pump inhibitors, including omeprazole, has not been shown in randomized clinical trials. The results of a number of observational studies are contradictory and do not give a clear answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications during the combined use of

Effect of drugs on the pharmacokinetics of omeprazole The isoenzymes CYP2C19 and CYP3A4 are involved in the metabolism of omeprazole. The combined use of omeprazole and inhibitors of the CYP2C19 and CYP3A4 isoenzymes, such as clarithromycin, erythromycin and voriconazole, may lead to an increase in the concentration of omeprazole in the blood plasma by slowing down the metabolism of omeprazole. Concomitant use of omeprazole and voriconazole results in a more than twofold increase in the AUC of omeprazole. Due to the good tolerance of high doses of omeprazole, short-term joint use of these drugs does not require dose adjustment of omeprazole. Drugs that induce the isoenzymes CYP2C19 and CYP3A4, such as rifampicin and St. John's wort preparations, when used together with omeprazole, can lead to a decrease in its concentration in the blood plasma due to accelerated metabolism of the drug. Co-administration of omeprazole with amoxicillin or metronidazole does not affect the concentration of omeprazole in the blood plasma.

Compound

1 capsule contains: omeprazole 20 mg.
Excipients: mannitol, sucrose, sodium lauryl sulfate, sodium hydrogen phosphate (disodium phosphate disubstituted), calcium carbonate, lactose, hypromellose (hydroxypropyl methylcellulose), methacrylic acid and ethyl acrylate copolymer (methacrylic acid copolymer L30D), propylene glycol, diethyl phthalate, cetyl alcohol, sodium hydroxide, polysorbate-80 (Tween-80), povidone (polyvinylpyrrolidone), titanium dioxide, talc. The capsules are opaque, hard gelatin, size No. 2, with a light pink body and a pinkish-brown cap. The contents of the capsules are white to almost white pellets.