Omeprazole Reneval, 20 mg 30 pcs.

Pharmacotherapeutic group: gastric secretion reducing agent – proton pump inhibitor.

ATX code: A02BC01

Pharmacological properties

Pharmacodynamics

Omeprazole is a racemic mixture of two enantiomers, reduces the secretion of hydrochloric acid by specific inhibition of the proton pump of gastric parietal cells. When administered once, it is fast acting and has a reversible inhibition of hydrochloric acid secretion.

Mechanism of action

. Omeprazole is a weak base, converts to its active form in the acidic environment of the tubules of the cells of the parietal layer of the gastric mucosa, where it is activated and inhibits H⁺/ K⁺-ATPase of the proton pump. It has a dose-dependent effect on
the last step of hydrochloric acid synthesis, inhibiting both basal and stimulated secretion regardless of the stimulating factor.

Influence on gastric hydrochloric acid secretion

After oral administration of omeprazole once daily, there is rapid and effective inhibition of daytime and nighttime hydrochloric acid secretion, which reaches a maximum within 4 days of treatment.

In patients with duodenal ulcer disease, use of 20 mg of omeprazole causes a sustained reduction of 24-hour gastric acidity by at least 80%. At the same time, a decrease in the average maximum concentration of hydrochloric acid after pentagastrin stimulation by 70% is achieved within 24 hours. Daily oral administration of 20 mg of omeprazole in patients with duodenal ulcer maintains the value of acidity at pH ≥ 3 for 17 hours on average.

The degree of inhibition of hydrochloric acid secretion is proportional to the area under the pharmacokinetic concentration-time curve (AUC) of omeprazole and is not proportional
to the actual plasma concentration of the drug at that time. No tachyphylaxis was observed during treatment with omeprazole.

Action on Helicobacter pylori

Omeprazole has a bactericidal effect on Helicobacter pylori in vitro. Eradication of Helicobacter pylori when using omeprazole in combination with antibacterial agents is accompanied by rapid elimination of symptoms, a high degree of healing of gastrointestinal (GI) mucosal defects and long-term remission of ulcer disease, which reduces the chance of complications such as bleeding as effectively as continuous maintenance therapy.

Other effects associated with inhibiting hydrochloric acid secretion

Patients taking drugs that decrease gastric gland secretion are more likely to have glandular cysts of the stomach floor over a long period of time. 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.

The decrease in gastric hydrochloric acid secretion by proton pump inhibitors or other gastric acid reducing agents leads to an increase in the growth of normal gut microflora, which in turn may lead to a small increase in the risk of intestinal infections caused by bacteria of the genus Salmonella spp. and Campylobacter spp, and, in hospitalized patients, probably also the bacteria Clostridium difficile.

During treatment with drugs that reduce gastric gland secretion, serum gastrin concentration increases. Due to decreased secretion of hydrochloric acid, plasma concentration of chromogranin A (CgA) increases. Increased plasma concentration of CgA may affect the results of examinations to detect neuroendocrine tumors. To prevent this effect, therapy with proton pump inhibitors should be suspended 5 days before the study of plasma CgA concentration determination. If plasma gastrin and CgA concentrations have not returned to normal values after 5 days, the study should be repeated 14 days after discontinuation of omeprazole.

In pediatric and adult patients on long-term omeprazole an increase in enterochromaffin-like cells was observed, probably related to an increase in serum gastrin concentrations. This phenomenon has no clinical significance.

Pharmacokinetics

Absorption

Omeprazole is rapidly absorbed from the gastrointestinal tract, the maximum concentration (C_max) in plasma is reached after 1-2 hours. Absorbed in the small intestine usually within 3-6 hours. Bioavailability after a single oral administration is about 40%, after continuous administration once a day bioavailability increases to 60%. Simultaneous intake of food does not affect the bioavailability of omeprazole.

Distribution

The binding of omeprazole to plasma proteins is about 95%, the volume of distribution is 0.3 l/kg.

Metabolism

Omeprazole is fully metabolized in the liver. The main isoenzymes involved in the process of metabolism are CYP2C19 and CYP3A4. Hydroxyomeprazole is the main metabolite formed under the action of CYP2C19 isoenzyme. Metabolites sulfone and sulfide have no effect on hydrochloric acid secretion.

Excretion

The half-life (T½) is about 40 minutes (30-90 minutes). About 80% is excreted as metabolites by the kidneys, the rest through the intestine.

Special patient groups

In elderly patients (75-79 years) a slight decrease in metabolism of omeprazole was noted.

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

The metabolism of omeprazole in patients with impaired liver function is delayed, resulting in increased bioavailability.

Indications

Adults:

Children over 2 years of age:

Children over 4 years of age:

Active ingredient

Composition

Omeprazole, pellet substance – 117.7 mg, – 235.3 mg

Pellet composition:

The active ingredient: omeprazole – 10.0 mg, – 20.0 mg;

Auxiliary substances: sucrose, mannitol (Pearlitol 160C)/mannitol, corn/maize starch, lactose monohydrate, sodium lauryl sulfate, sodium phosphate displaced, hydroxypropyl-methylcellulose; coating excipients: methacrylic acid copolymer, dispersion (L30D), hypromellose, propylene glycol, cetyl alcohol, titanium dioxide, mannitol (Pearlitol 160C)/mannitol, polysorbate – 80, sodium hydroxide 1.3815 q 18

The hard gelatin capsule:

capsule body composition: gelatin; capsule cap composition: gelatin, azorubin – carmoisin

How to take, the dosage

Ingestion.

The capsules are usually taken in the morning, preferably separately from food, swallowed whole with half a glass of water. The capsules should not be chewed or crushed.

If swallowing is difficult, the contents of the capsule may be mixed with a slightly acidic liquid (juice, yogurt) and used within 30 minutes after opening.

Dosage 20 mg

In an exacerbation of duodenal ulcer, it is recommended to take the drug at 20 mg once a day. Usually the therapy duration is 2 weeks; if necessary, it is possible to increase the course of therapy for another 2 weeks. Patients with duodenal ulcer resistant to treatment are usually prescribed the drug 40 mg 1 time per day for 4 weeks. For relapse prevention in patients with duodenal ulcer, 20 mg once daily; in some cases 10 mg once daily may be sufficient (capsules containing 10 mg of omeprazole must be taken). If necessary, the dose may be increased to 40 mg once daily.

In acute peptic ulcer disease, the recommended dose of the drug is 20 mg once daily. The duration of therapy is 4 weeks. In cases when after the first course of the drug full healing does not occur, a repeated 4-week course of treatment is prescribed. Patients with gastric ulcer disease resistant to treatment are usually prescribed the drug 40 mg 1 time per day, healing is usually achieved within 8 weeks. For prevention of relapse, patients with peptic ulcer disease are recommended to take the drug in a dose of 20 mg once daily. If necessary, the dose can be increased to 40 mg once a day.

Modes of eradication of Helicobacter pylori in peptic ulcer disease:

– omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg simultaneously 2 times a day for 1 week;

– omeprazole 20 mg, clarithromycin 250 mg (alternatively, 500 mg), metronidazole 400 mg (or 500 mg, or tinidazole 500 mg) simultaneously 2 times daily for 1 week;

– omeprazole 40 mg once daily and amoxicillin 500 mg with metronidazole 400 mg (or 500 mg, or tinidazole 500 mg) both 3 times daily for 1 week.

In cases where the patient is Helicobacter pylori positive after treatment, a second course of treatment is possible.

The recommended dose of omeprazole is 20 mg once daily. The course of treatment is 4 weeks. For patients in whom the ulcer has not healed, the course may be prolonged for another 4 weeks.

. As prophylaxis of NSAID-associated gastric and duodenal ulcerative erosive lesions in patients at risk (age >60 years, history of gastric and duodenal ulcers, history of upper GI bleeding) the recommended dose is 20 mg omeprazole once daily.

The recommended dose is 20 mg omeprazole once daily. The course of treatment is 4 weeks. For patients who are not cured during this period, the course may be prolonged by 4 weeks. For severe esophagitis, the recommended dose is 40 mg omeprazole once daily and the course of treatment is 8 weeks.

For maintenance therapy in patients with reflux esophagitis, the recommended dose of omeprazole is 10 mg once daily (10 mg omeprazole capsules should be taken). If necessary, the dose may be increased to 20-40 mg once daily.

The recommended dose is 20 mg once daily. Individual adjustment of the dose is possible.

If symptoms persist after 4 weeks of treatment at a dose of 20 mg omeprazole daily, further evaluation is required.

The usual dose is 10 mg daily. The maximum daily dose of the drug should not exceed 20 mg. The maximum course of treatment is 14 days. If within 2 weeks there is no relief of symptoms or they worsen, it is necessary to consult a physician.

The dose is set individually. The recommended starting dose is 60 mg once daily. If necessary, the dose is increased to 80-120 mg per day. If the dose is over 80 mg, it should be divided into 2 doses.

– In children over 2 years of age with a body weight greater than 20 kg, the recommended dose is 20 mg once daily. The dose may be increased to 40 mg once daily if necessary.

The course of treatment in reflux esophagitis is 4-8 weeks, in symptomatic treatment of heartburn and belching sourness in GERD – 2-4 weeks. If the symptoms persist after 2-4 weeks, the patient requires further examination.

. When choosing the appropriate combination therapy, official local and national recommendations in terms of bacterial resistance, duration of treatment (most often 7 days, but sometimes up to 14 days may be required) and appropriate antibacterial agents must be taken into account.

The treatment is supervised by a specialist.

– In children with a body weight of 15-30 kg:use in combination with two antibiotics: omeprazole 10 mg, clarithromycin and amoxicillin in this category of patients are prescribed in a dosing regimen according to the guidelines for clarithromycin and amoxicillin (used simultaneously 2 times a day for 1 week).

– In children with a body weight of 31-40 kg:use in combination with two antibiotics: omeprazole 20 mg, clarithromycin and amoxicillin in this category of patients are prescribed in dosing regimens according to the instructions for the use of clarithromycin and amoxicillin (used simultaneously 2 times a day for 1 week).

– In children with a body weight greater than 40 kg:use in combination with two antibiotics: omeprazole 20 mg, clarithromycin and amoxicillin in this category of patients are prescribed in dosing regimens according to the instructions for clarithromycin and amoxicillin (used simultaneously 2 times a day for 1 week).

In case of hepatic insufficiency, 10-20 mg (maximum daily dose 20 mg) once daily; no dosing adjustment is required in impaired renal function and in elderly patients.

Interaction

Actives with pH-dependent absorption

Lowering gastric acidity with omeprazole may increase or decrease absorption of pharmacologically active substances.

Nelfinavir, atazanavir

Concomitant use with omeprazole may significantly decrease plasma concentrations of atazanavir and nelfinavir.

The concomitant use of omeprazole and nelfinavir is contraindicated. Concomitant use of omeprazole (40 mg daily) reduces exposure to nelfinavir by approximately 40% and the average exposure to the pharmacologically active metabolite M8 is reduced by 75-90%. The mechanism of CYP2C19 inhibition may be involved in the interaction.
Concomitant use of omeprazole with atazanavir is not recommended. Concomitant use of omeprazole (40 mg daily) and atazanavir 300 mg/ritonavir 100 mg in healthy volunteers resulted in a 75% reduction in atazanavir exposure. Increasing the atazanavir dose to 400 mg does not compensate for the effect of omeprazole on atazanavir exposure. Using 20 mg of omeprazole daily with 400 mg of atazanavir and 100 mg of ritonavir in healthy volunteers resulted in approximately 30% reduction in atazanavir exposure and was comparable to exposure with a single dose of 300 mg of atazanavir and 100 mg of ritonavir. If atazanavir and omeprazole cannot be coadministered, close patient monitoring is recommended and the atazanavir dose should be increased to 400 mg with ritonavir at 100 mg, and the omeprazole dose should not exceed 20 mg daily.

Digoxin

The concomitant treatment with omeprazole (20 mg daily) and digoxin in healthy volunteers increased the bioavailability of digoxin by 10%. Although glycoside intoxication with omeprazole is not a frequent event, increased monitoring is necessary, especially when treating elderly patients.

Clopidogrel

. A pharmacokinetic/pharmacodynamic interaction has been observed between clopidogrel (loading dose 300 mg, maintenance dose 75 mg/day) and omeprazole (80 mg/day orally) that reduces exposure to the active metabolite clopidogrel by 46% (day 1) and 42% (day 5) and reduces mean platelet aggregation inhibition time by 47% (24 hours) and 30% (day 5). It has also been shown that taking clopidogrel and omeprazole at different times does not prevent their interaction, which is probably due to the inhibitory effect of omeprazole on CYP2C19. The results of several observational studies are inconsistent and do not provide a definite answer about the presence or absence of an increased risk of thromboembolic cardiovascular complications with clopidogrel and proton pump inhibitors concomitantly used.

Other drugs

The absorption of posaconazole, erlotinib, ketoconazole and itraconazole is significantly reduced, respectively, worsens their clinical effectiveness. Co-administration of omeprazole with posaconazole or erlotinib should be avoided.

Drugs metabolized by the CYP2C19 isoenzyme

Omeprazole moderately inhibits CYP2C19, the main enzyme of metabolism of omeprazole. Thus, the metabolism of other drugs that are also metabolized by CYP2C19 may be reduced and their systemic effects may be increased. Examples of such drugs are R-warfarin and other vitamin K antagonists, cilostazol, diazepam, and phenytoin. International normalized ratio (INR) monitoring is necessary when using omeprazole in patients receiving warfarin or other vitamin K antagonists; in some cases, it may be necessary to reduce the dose of warfarin or other vitamin K antagonist. In contrast, concomitant treatment with omeprazole at a daily dose of 20 mg does not alter the coagulation time in patients on long-term warfarin.

Omeprazole does not affect metabolism of drugs metabolized by CYP3A4 isoenzyme, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin and budesonide.

Omeprazole has not been found to interact with the following drugs: antacids, caffeine, theophylline, S-warfarin, piroxicam, diclofenac, naproxen, metoprolol, propranolol and ethanol.

Methotrexate

In some patients a slight increase in plasma concentrations of methotrexate was noted with concomitant use with proton pump inhibitors. If high doses of methotrexate are prescribed, temporary discontinuation of omeprazole should be considered.

Cilostazol

The use of omeprazole in dose of 40 mg once daily led to increase of maximal plasma concentration and AUC of cilostazol by 18% and 26%, respectively; for one of the active metabolites of cilostazol the increase was 29% and 69%, respectively.

Phenytoin

Phenytoin plasma concentration monitoring is recommended for the first 2 weeks after initiation of omeprazole therapy and if the phenytoin dose is adjusted; monitoring and subsequent adjustment of the phenytoin dose should be performed until completion of omeprazole treatment.

Unknown mechanism of interaction

Saquinavir

. Co-administration of omeprazole and saquinavir/ritonavir is well tolerated in HIV-infected patients and also results in increased plasma concentrations of saquinavir up to about 70%.

Tacrolimus

The co-administration with omeprazole increases the serum concentration of tacrolimus. Increased monitoring of tacrolimus concentrations and renal function (creatinine clearance) should be performed with dose adjustments of tacrolimus if necessary.

Influence of other drugs on the pharmacokinetics of omeprazole

Inhibitors of CYP2C19 and/or CYP3A4 isoenzyme

. Given the metabolism of omeprazole involving the CYP2C19 and CYP3A4 isoenzymes, drugs that can inhibit these enzymes (such as clarithromycin and voriconazole) can increase the serum concentration of omeprazole, slowing its metabolic rate. Concomitant use of voriconazole and omeprazole leads to more than twice the AUC of omeprazole. Due to good tolerability of high doses of omeprazole, no dose adjustment of omeprazole is required with short-term concomitant use of these drugs.

The concomitant use of omeprazole with amoxicillin or metronidazole does not affect the plasma concentration of omeprazole.

Drugs inducing CYP2C19 and CYP3A4 isoenzymes, such as rifampicin and St. John’s Wort preparations, when used concomitantly with omeprazole may decrease the plasma concentration of omeprazole by accelerating the metabolism of omeprazole.

Special Instructions

Before initiating therapy, the presence of a malignant process in the upper gastrointestinal tract should be excluded, as taking omeprazole may mask symptoms and delay a correct diagnosis. Decreased gastric acidity, including with proton pump blockers, increases the number of bacteria in the gastrointestinal tract, which increases the risk of gastrointestinal infections.

Elevated CgA concentrations may affect neuroendocrine tumor screenings. To prevent this effect, omeprazole should be temporarily stopped 5 days before the CgA study. If plasma CgA and gastrin concentrations have not normalized after initial measurement, a control study should be performed 14 days after proton pump inhibitor treatment is stopped.

In patients with significant liver function impairment, liver enzymes should be monitored regularly during therapy with omeprazole.

The drug contains sucrose and therefore is contraindicated in patients with congenital carbohydrate metabolism disorders (fructose intolerance, insufficiency of sucrose/isomaltase, glucose-galactose malabsorption syndrome).

In the therapy of ulcer-erosive lesions associated with taking NSAIDs, careful consideration should be given to limiting or discontinuing NSAIDs to improve the effectiveness of antiulcer therapy.

The drug contains sodium, which should be considered in patients on a controlled sodium diet.

The risk-benefit ratio of long-term (>1 year) maintenance therapy with omeprazole should be regularly evaluated. There are data on increased risk of vertebral fractures, carpal bones, femoral head mainly in elderly patients, as well as in the presence of predisposing factors. Patients at risk for osteoporosis should have adequate vitamin D and calcium intake.

There have been reports of severe hypomagnesemia in patients receiving therapy with proton pump inhibitors, including omeprazole, for more than 1 year.

Patients receiving therapy with omeprazole for a long time, especially in combination with Digoxin or other drugs that reduce plasma magnesium (diuretics), require regular monitoring of magnesium.

Omeprazole, like all acid-reducing drugs, may decrease absorption of vitamin B12 (cyanocobalamin). This should be kept in mind in patients with reduced vitamin B12 reserves in the body or with risk factors for impaired vitamin B12 absorption during long-term therapy.

The formation of glandular cysts in the stomach has been observed more frequently in patients who have taken drugs that decrease gastric gland secretion orally for a long period of time. These phenomena are due to physiologic changes resulting from inhibition of hydrochloric acid secretion and are reversed with continuation of therapy.

The decrease in secretion of hydrochloric acid in the stomach leads to an increase in the growth of normal intestinal microflora, which in turn may lead to a slightly increased risk of intestinal infections caused by bacteria of Salmonella spp. and Campylobacter spp, and probably Clostridium difficile.

The use of proton pump inhibitors is associated with extremely rare cases of subacute cutaneous lupus erythematosus (SLE). Patients should seek medical attention immediately if there are abnormal skin changes, particularly in exposed skin, accompanied by arthralgia. The physician should consider withdrawing omeprazole. Patients with PKV on prior proton pump inhibitor therapy have an increased risk of PKV on subsequent therapy with other proton pump inhibitors.

Impact on ability to drive, machinery

With regard to the possibility of occurrence of HP in central nervous system and vision, during treatment with omeprazole, caution should be exercised when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and rapid psychomotor reactions.

Synopsis

Contraindications

Hypersensitivity to omeprazole or any of the ingredients of the drug; fructose intolerance; sucrose/isomaltase deficiency; glucose-galactose malabsorption syndrome; simultaneous use with clarithromycin in patients with hepatic impairment; atazanavir, St. John’s wort, erlotinib, posaconazole.

Dosage 20 mg

With caution

Liver function deficiency; renal function deficiency; osteoporosis; concomitant use with clarithromycin, clopidogrel, itraconazole, warfarin, cilostazol, diazepam, phenytoin, saquinavir, tacrolimus, voriconazole, rifampicin; significant spontaneous weight loss; recurrent vomiting, vomiting with blood; impaired swallowing; discolored stools (tarry stools); and, if peptic ulcer is present (or suspected), malignancy should be excluded before starting treatment, as treatment may mask symptoms and delay correct diagnosis.

Side effects

The following are the adverse reactions (ARs) that have been identified in clinical trials as well as in the clinical use of omeprazole.

The following criteria were used to assess the frequency of NRs: “very common” (≥ 1/10); “common” (≥ 1/100, < 1/10); “infrequent” (≥ 1/1000, < 1/100); “rare” (≥ 1/10000, < 1/1000); “very rare” (< 1/10000). HPs are grouped according to the system-organ classes of the MedDRA Medical Regulatory Dictionary, within each class HPs are listed in descending order of frequency of occurrence, within each group allocated by frequency of occurrence HPs are allocated in decreasing order of importance.

Blood and lymphatic system involvement: frequently, hypochromic microcytic anemia in children; very rarely, reversible thrombocytopenia, leukopenia, pancytopenia, agranulocytosis.

Con the side of the immune system: very rarely – rash, increased body temperature, angioedema, bronchospasm, allergic vasculitis, fever, anaphylactic reactions/shock.

Nervous system disorders: frequent – headache, drowsiness, lethargy (the listed HRs find a tendency to worsen with long-term therapy); infrequent – insomnia, dizziness; rare – paresthesias, confusion, hallucinations, especially in older patients or with a severe course of the disease; very rare – anxiety, depression, especially in older patients or with a severe course of the disease.

Overlooking organ: infrequent – visual disturbances, including decreased visual fields, decreased visual acuity and clarity (usually subsides after
discontinuation of therapy).

Hearing organ and labyrinth disorders: infrequent – vertigo, auditory perception disorders, including “ringing in the ears” (usually goes away after discontinuation of therapy).

Gastrointestinal tract disorders: often – nausea, vomiting, flatulence, constipation, diarrhea, abdominal pain (in most cases the severity of these phenomena increases with continuation of therapy), glandular polyps of the fundamental part of the stomach (benign); rarely – taste disorder, discoloration of the tongue to brownish-black, and appearance of benign salivary gland cysts when concomitantly used with clarithromycin (the phenomena are reversible after discontinuation of therapy), microscopic colitis; very rarely – dry mouth, stomatitis, candidiasis, pancreatitis.

Hepatic and biliary tract disorders: frequent – changes in the activity of “liver” enzymes (reversible nature); very rare – hepatitis, jaundice, liver failure, encephalopathy in patients with background liver disease.

Skin and subcutaneous tissue disorders: infrequent – urticaria, rash, pruritus, alopecia, erythema multiforme, photosensitization, increased sweating; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis.

Some cases of skeletal-muscular and connective tissue disorders: frequently – fractures of vertebrae, carpal bones, femoral head (see section “Cautions”); rarely – myalgia and arthralgia; very rarely – muscle weakness.

Repnal and urinary tract disorders: frequently – interstitial nephritis.

General disorders and disorders at the site of administration: infrequent – peripheral edema (usually resolves after discontinuation of therapy); rare – hyponatremia; very rare – gynecomastia; frequency unknown – hypomagnesemia (see section “Special Indications”).

Overdose

Symptoms: Vomiting, abdominal pain, diarrhea, dizziness, depression, visual disturbance, drowsiness, agitation, confusion, headache, increased sweating, dry mouth, nausea, arrhythmia.

Treatment:conducting symptomatic therapy, hemodialysis is not sufficiently effective. A specific antidote is unknown.

Pregnancy use

Pregnancy

The results of studies indicate no adverse effects on pregnancy, fetal or newborn health. Omeprazole may be used with caution in pregnancy.

Breastfeeding

Omeprazole is excreted with breast milk. However, when used in therapeutic doses, effects on the baby are unlikely.

Similarities