Description
Pharmacological action
Pharmacodynamics
The combination of two active substances (domperidone and omeprazole) has a complex effect on the main pathogenesis of gastroesophageal reflux disease (GERD), dyspeptic disorders of various origins. Domperidone enhances and synchronizes physiological peristaltic waves, omeprazole reduces basal and stimulated secretion of hydrochloric acid.
Omeprazole
Mechanism of Action
Omeprazole is concentrated in the acidic environment of the secretory tubules of the parietal cells of the gastric mucosa, and the proton pump is activated and inhibits the enzyme H + / K + ATPase, which provides a dose-dependent highly effective inhibition of basal and stimulated secretion of hydrochloric acid, regardless of the stimulating factor.
Effect on gastric acidity
The maximum effect is achieved within 4 days of treatment. In patients with a duodenal ulcer, omeprazole at a dose of 20 mg causes a steady decrease of 24 hourly gastric acidity of not less than 80%. This achieves a decrease in the average maximum concentration of hydrochloric acid after stimulation with pentagastrin by 70% within 24 hours. In patients with duodenal ulcer, omeprazole 20 mg, with daily oral administration, maintains an intragastric pH value of pH 3 for an average of 17 hours a day. Inhibition of hydrochloric acid secretion depends on the area under the pharmacokinetic curve “concentration – time” (AUC) of omeprazole, and not on the concentration of the drug in plasma at a given time.
Effects on Helicobacter pylori
Eradication of Helicobacter pylori with omeprazole in combination with antibacterial agents is accompanied by a rapid elimination of symptoms, a high degree of healing of gastric mucosa defects intestinal tract and prolonged remission of peptic ulcer, which reduces the likelihood of complications such as bleeding, as effective as continuous maintenance therapy.
Other effects of
A decrease in the secretion of hydrochloric acid in the stomach leads to a slight increase in the risk of intestinal infections caused by Salmonella spp., Campylobacter spp. and Clostridium difficile. During treatment with drugs that lower the secretion of the glands of the stomach, the concentration of gastrin in the blood serum rises. Due to a decrease in the secretion of hydrochloric acid, the concentration of chromogranin A increases (see section “Special instructions”).
Domperidone
A dopamine antagonist that combines peripheral (gastrokinetic) action and antagonism to dopamine receptors in the trigger zone of the brain (central effect), due to which it has an antiemetic effect, stimulates the release of prolactin from the pituitary gland and eliminates the inhibitory effect of dopamine on gastrointestinal function intestinal tract, enhances and synchronizes peristaltic waves, thereby accelerating the natural emptying of the stomach and increases the pressure of the sphincter of the lower esophagus.
Pharmacokinetics
Omeprazole
Absorption of omeprazole is high, the time to reach maximum plasma concentration (TCmax) is 0.5 1 hour. Bioavailability – 30 40%, after continuous use
1 time per day increases to 60%.
distribution. Communication with plasma proteins – 90 95% Distribution volume 0.3 l / kg. Metabolism. Part of omeprazole undergoes a presystemic hepatic metabolism with the participation of CYP2C19 more than CYP3A4 with the formation of inactive metabolites. Omeprazole, not included by parietal cells in the formation of active metabolites, is completely metabolized in the liver. The total plasma clearance is 0.3 0.6 l / min.
Withdrawal. The half-life (T1 / 2) of omeprazole is about 40 minutes. It is excreted by the kidneys (70 ² 80%) and with bile (20 ² 30%).
In case of impaired liver function, bioavailability increases and plasma clearance of omeprazole decreases. In case of impaired renal function or in elderly patients, no changes in the bioavailability of omeprazole were noted.
Domperidone
This dosage form provides a sustained release of the active substance. In dissolution tests in an acidic medium after 8 hours, from 75% to 83% of the nominal content of domperidone in one capsule is determined, and after 12 hours from 86% to 94%.
Fast absorption on an empty stomach. TCmax – 30 60 minutes Low bioavailability (15%) is associated with the first-pass metabolism in the intestinal wall and liver.
distribution. Communication with plasma proteins – 90%. Penetrates into various tissues, poorly passes through the blood-brain barrier.
Metabolized in the liver (including due to the effect of the first passage) and in the intestinal wall (by hydroxylation and N dealkylation) with the participation of isoenzymes CYP3A4, CYP1A2 and CYP2 1.
Excretion: 66% through the intestines (unchanged – 10%), kidneys – 33% (unchanged 1%) in the form of glucuronides. In severe chronic renal failure, T1 / 2 lengthens.
Indications
Indigestion dyspepsia, accompanied by delayed gastric emptying esophageal reflux, esophagitis (a feeling of fullness in the epigastrium, a feeling of bloating, pain in the upper abdomen, belching, flatulence, nausea, vomiting of heartburn with or without refluxing the gastric contents into the oral cavity)
gastroesophageal reflux disease of sore throat, srdlp gastroesophageal reflux disease, gastritis, peptic ulcer of the stomach and duodenum, including after eradication therapy.
Contraindications
Hypersensitivity to omeprazole, substituted benzimidazoles, or other components of the drug.
Sucrose / isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption (due to the presence of sucrose in the formulation).
Concomitant use with erlotinib, posaconazole, nelfinavir and atazanavir.
The use of omeprazole in children is contraindicated, except as indicated: gastroesophageal reflux disease for children older than 2 years and duodenal ulcer caused by Helicobacter pylori for children older than 4 years (see section “Dosage and administration”).
Before using the drug, it is necessary to consult a doctor in the following cases: in the presence of a previously diagnosed stomach ulcer of a serious liver disease, accompanied by liver failure of renal failure of jaundice previous surgical intervention on the gastrointestinal tract
in the presence of disturbing symptoms: a significant spontaneous decrease in body weight repeated vomiting, vomiting with an admixture of blood, a change in the color of feces (tarry stool – melena), impaired swallowing of
when new symptoms appear or changes in existing symptoms of the gastrointestinal tract
with simultaneous use with one or more of the following drugs: clopidogrel, digoxin, ketoconazole, itraconazole, warfarin, cilostazole, diazepam, phenytoin, tacrolin , clarithromycin, voriconazole, rifampicin, preparations of St. John’s wort perforated (see the section “Interaction with other medicines”).
Osteoporosis. Although a causal relationship with the use of omeprazole with fractures associated with osteoporosis has not been established, patients with a risk of developing osteoporosis or fractures against its background should be under appropriate clinical supervision.
Use during pregnancy and lactation
Use of Omez ® DSR during pregnancy and during breast-feeding is contraindicated.
Special instructions
Lactose
Omeprazole granules contain lactose, so do not use Omez ® DSR in patients with lactose intolerance, galactosemia and glucose and galactose malabsorption.
Cardiovascular system
It has been shown that the use of domperidone may be associated with an increased risk of ventricular arrhythmias or sudden coronary death, which is more likely for patients over 60 with a daily dose of domperidone greater than 30 mg. The use of domperidone and other drugs, leading to lengthening of the QT interval requires caution in patients with existing conduction disturbances with QT lengthening, severe electrolyte imbalance or congestive heart failure).
Osteoporosis
Patients at risk of developing osteoporosis or fractures in the background should be under appropriate clinical supervision, although a causal relationship with the use of omeprazole with fractures in the setting of osteoporosis has not been established.
Hypomagnesemia
There are reports of severe hypomagnesemia in patients receiving proton pump inhibitor therapy, including omeprazole, for more than one year. Patients receiving omeprazole therapy for a long time, especially in combination with digoxin or other drugs that reduce plasma magnesium (diuretics), regular monitoring of magnesium content is required.
During treatment with Omez ® DSR, care should be taken when driving vehicles and performing other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.
Composition
Each capsule contains: active ingredients: omeprazole 20 mg (in the composition of enteric-coated granules 267 mg), domperidone 30 mg (in the composition of granules with sustained release 100 mg) excipients: talc 2 mg.
Composition of omeprazole granules: active ingredient: omeprazole 20 mg excipients: mannitol 137.86 mg, lactose monohydrate 9.66 mg, sodium lauryl sulfate 0.52 mg, sodium hydrogen phosphate 0.89 mg, sucrose (25/30) 24.35 mg, sucrose 8.54 mg, hypromellose 6 cps 0.14 mg coating: hypromellose 6 cps 13 mg enteric coating: methacrylic acid and ethyl acrylate copolymer [1: 1] (methacrylic acid copolymer [type C]) 40.47 mg, sodium hydroxide 0.54 mg, macrogol 6000 4.85 mg, talc 4.05 mg, titanium dioxide 2.13 mg.
Composition of domperidone granules: active ingredient: domperidone 30 mg
excipients: nonparel sugar grains 58.98 mg, colloidal silicon dioxide 0.48 mg, talc 4.51 mg, hypromellose 5 cps 0.57 mg coating: hypromellose 5 cps 2 , 34 mg, talc 0.71 mg, iron dye yellow oxide 0.12 mg, iron dye red oxide 0.04 mg, titanium dioxide 0.47 mg extended release coating: hypromellose 5 cps 0.40 mg, ethyl cellulose 10 cps 1 , 18 mg, triacetin 0.12 mg, talc 0.086 mg.
Composition of gelatin hard capsules No. 1: gelatin 85.42%, water 14.50%, sodium lauryl sulfate 0.08%.
Composition of black ink for the inscription on the capsule cap: ethanol 29 33%, isopropanol 9 12%, butanol 4 7%, shellac 24 28%, dye iron oxide black (E172) 24 28%, ammonia water 1 3%, propylene glycol 0.5 2%
Composition of red ink for inscription on the capsule body: ethanol 21 25% isopropanol 12 16%, butanol 7 10%, shellac 22 27%, crimson dye [Ponceau 4R] (E124) 18 24%, titanium dioxide (E171) 5 9%, ammonia water 1 3%, polysorbate 80 0.5 2%, propylene glycol 0.5 2%
Dosage and administration
Omez ® DSR is taken orally on an empty stomach, 20-30 minutes before a meal (the contents of the capsule cannot be chewed), washed down with a small amount of water.
Omez ® DSR is taken one capsule once a day in the morning.
The maximum daily dose is 1 capsule of Omez ® DSB, which corresponds to 20 mg of omeprazole and 30 mg of domperidone.
Use for impaired liver function. For mild hepatic impairment, dosage adjustment is not required.
Use for impaired renal function. Single dose adjustment is not required.
Use in the elderly. No dosage adjustment is required.
Side effects
Possible side effects are given below for body systems and frequency of occurrence for omeprazole and domperidone: very often (> 1/10) often (? 1/100, <1/10) infrequently (? 1/1000, <1 / 100) rarely (? 1/10000, <1/1000) very rarely (<1/10000, including isolated cases and frequency is not known). Disorders of the blood and lymphatic system Omeprazole – rarely: leukopenia, thrombocytopenia very rarely: agranulocytosis, pancytopenia, eosinophilia. Immune system disorders Omeprazole – rarely: hypersensitivity reactions: fever, angioedema, anaphylactic reaction / anaphylactic shock. Domperidone is very rare: anaphylactic reaction / anaphylactic shock, angioedema. Metabolism and nutritional disorders Omeprazole – rare: hyponatremia frequency unknown: hypomagnesemia, which in severe cases can lead to hypocalcemia, hypokalemia. Mental disorders Omeprazole – infrequently: insomnia rarely: irritability, depression, reversible confusion is very rare: aggression, hallucinations. Domperidone is very rare: agitation, nervousness, increased irritability and irritability. Disturbances from the nervous system Omeprazole – often: headache infrequently: dizziness, paresthesia, drowsiness rarely: taste disturbance. Domperidone is very rare: extrapyramidal effects, convulsions, drowsiness, headache. Visual disturbances Omeprazole – infrequently: visual disturbances, including decreased visual fields, decreased visual acuity and clarity (usually go away after therapy is stopped). Hearing impairment and labyrinthine disorders Omeprazole – infrequently: hearing impairment, including tinnitus (usually disappears after discontinuation of therapy), vertigo (a feeling of spinning your own body or surrounding objects). Disorders from the cardiovascular system: Domperidone – very rare: prolonged QT interval, ventricular tachycardia of the pirouette type, sudden coronary death (more likely for patients over 60 years of age, taking more than 30 mg per day). Disorders of the respiratory system, chest and mediastinal organs: Omeprazole – rarely: bronchospasm. Disorders of the gastrointestinal tract Omeprazole – often: abdominal pain, constipation, diarrhea, flatulence, nausea, vomiting rarely: dry oral mucosa, stomatitis, gastrointestinal candidiasis, microscopic colitis, discoloration of the tongue to brown-black and the appearance of benign salivary gland cysts when used simultaneously with clarithromycin (phenomena are reversible after discontinuation of therapy) isolated cases: the formation of gastric glandular cysts and during prolonged treatment with simultaneous use with clarithromycin (due to inhibition of hydrochloric acid secretion , is benign, reversible). Disorders from the liver and biliary tract Omeprazole – infrequently: increased activity of liver enzymes and alkaline phosphatase (reversible) rarely: hepatitis (with or without jaundice), liver failure, encephalopathy in patients with previous severe liver diseases. Disorders of the skin and subcutaneous tissue Omeprazole – infrequently: dermatitis, pruritus, skin rash, urticaria rarely: alopecia, photosensitivity reactions in the form of reddening of the skin after UVD, erythema multiforme exudative, toxic epidermal necrolysis, Stevens-Johnson syndrome (severe erythema, characterized by the appearance of spots and blisters on the skin and mucous membranes against a background of high temperature and pain in pain joints). Domperidone – very rare: Quincke’s edema, urticaria. Musculoskeletal and connective tissue disorders Omeprazole – infrequently: vertebral, wrist, femoral head fractures associated with osteoporosis rarely: arthralgia, myalgia, muscle weakness. Disorders of the kidneys and urinary tract Omeprazole – rare: interstitial nephritis. Domperidone – very rare: urinary retention. Genital and breast disorders Omeprazole – rarely: gynecomastia. General disorders Omeprazole – infrequently: malaise rarely: excessive sweating, peripheral edema. Laboratory and instrumental data Domperidone – very rare: changes in liver function tests, elevated blood prolactin levels. In case of side effects not listed in these instructions, you should immediately inform your doctor. Drug Interactions Omeprazole A potential metabolic interaction between omeprazole and other drugs is highly unlikely. However, since omeprazole delays the hepatic microsomal metabolism of drugs (cytochrome P450 enzyme system), the elimination of other drugs that require hepatitis metabolism via the cytochrome P450 enzyme system, or which is highly extracted for the liver, can be reduced during the concomitant use of omeprazole. Such an effect may be a consequence of further delayed withdrawal of the drug, an increase in the concentration of diazepam, diphenin and anticoagulants in the blood concentration, such as warfarin (control of blood concentration or prothrombin time, which is recommended in the further choice of dosage, after the initial dosage necessary during the entire period of treatment with omeprazole is determined). Omeprazole, by increasing the pH level in the stomach, can subsequently affect the bioaccumulation of any drugs for which the absorption is pH-dependent, and omeprazole can prevent a decrease in the effect of acid-changing drugs on the body. Therefore, the concomitant use of itraconazole and ketoconazole together with omeprazole can lead to a decrease in the absorption level of these drugs. Omeprazole does not affect any other significantly important CYP isoforms, resulting in a loss of metabolic interaction with the main substances for the formation of CYP1A2 (caffeine, phenacetin, aminophylline), CYP2C9 (S-warfarin), CYP2D6 (metoprolol, propranolol), CYP2E1, (ethanol) and CYP3A (cyclosporine, iodocaine, quinidine, estradiol, erythromycin). No strong effect of omeprazole on the steady state pharmacokinetics of piroxicam, diclofenac and naproxen was observed during the study of healthy patients in the process of receiving repeated doses of omeprazole 20 mg. Domperidone Positive effects of domperidone may be associated with concomitant cholinergic drugs. Since domperidone is used as a drug prescribed to improve the low motility of the gastrointestinal tract, the absorption of this drug can be accelerated in the small intestine, while the absorption of this drug through the stomach is very slow. Caution is advised when combining domperidone with monoamine oxidase inhibitors. The absorption of domperidone was not reduced when taken in combination with antacids or drugs that block H2 receptors. The main role in domperidone metabolism is played by the CYP3A4 isoenzyme. The results of in vitro studies and clinical experience show that the simultaneous use of drugs that significantly inhibit this isoenzyme can cause an increase in plasma concentrations of domperidone. Potential CYP3A4 inhibitors include: Azole antifungals such as fluconazole *, itraconazole, ketoconazole * and voriconazole * Macrolide antibiotics, such as clarithromycin * and erythromycin * HIV, antiviral antiviral agents, for example, antiviral inhibitors , indinavir, nelfinavir, ritonavir and sahinavir Calcium antagonists such as diltiazem and verapamil Amiodarone * Aprepitant Nefazodon. Telithromycin * (Drugs marked with an asterisk also extend the QT interval (see section “Contraindications”). Overdose Omeprazole Symptoms: confusion, drowsiness, headache, blurred vision, tachycardia, dry mouth, nausea, sweating. Treatment: gastric lavage, activated charcoal intake, symptomatic therapy. Domperidone Symptoms: drowsiness, disorientation and extrapyramidal reactions, impaired vision, drowsiness, agitation, confusion, headache, increased sweating, dry mouth, nausea, arrhythmia. Treatment: intake of activated charcoal, if extrapyramidal reactions occur – anticholinergic, antiparkinsonian, antihistamines. There is no specific antidote. Hemodialysis is ineffective. Storage conditions At a temperature not exceeding 25 ° C. Keep out of the reach of children! Expiration 2 years. Deystvuyuschee substances Omeprazole, Domperydol pharmacy terms for prescription Form of Treatment kapsul
