Instructions for Omez D hard capsules strip No. 30
Composition
active ingredients: omeprazole and domperidone;
1 capsule contains: omeprazole 10 mg, domperidone 10 mg;
Excipients: microcrystalline cellulose, sodium starch glycolate (type A); colloidal anhydrous silica; mannitol (E 421); sucrose; disodium hydrogen phosphate; sodium lauryl sulfate; magnesium stearate; talc; lactose monohydrate; calcium carbonate; hypromellose; propylene glycol, methacrylate copolymer (type C); polysorbates, diethyl phthalate; sodium hydroxide, cetyl alcohol, corn starch.
Dosage form
The capsules are hard.
Main physicochemical properties: hard gelatin capsules with a blue to purple cap and the inscription OMEZ D in white, with a body from almost white to white with a logo applied
black in color, containing off-white to white pellets and powdery mass.
Pharmacotherapeutic group
Drugs for the treatment of peptic ulcer and gastroesophageal reflux disease. ATC code A02B C.
Pharmacological properties
Pharmacodynamics.
A drug whose action is due to the components that make up its composition. Omeprazole is an antisecretory antiulcer agent that reduces spontaneous and stimulated gastric secretion by inhibiting the H+/K+-ATPase (proton pump), which is necessary for the transport of hydrogen ions. It inhibits the final phase of basal and stimulated secretion of hydrochloric acid, regardless of the nature of the stimulus.
Domperidone is a dopamine receptor antagonist, prokinetic. It practically does not penetrate the BBB. It increases the duration of peristaltic contractions of the antrum of the stomach and duodenum, increases the rate of gastric emptying, increases the tone of the lower esophageal sphincter. It does not disrupt digestive secretion. It exhibits an antiemetic effect, which is a combination of gastrokinetic action and antagonism to dopamine receptors in the chemoreceptor trigger zone, which is located outside the BBB.
Pharmacokinetics.
Omeprazole.
Omeprazole is rapidly absorbed. Peak plasma concentrations are reached 1-2 hours after oral administration. Absorption of omeprazole occurs in the small intestine and is usually complete within 3-6 hours. Concomitant food intake does not affect the bioavailability of omeprazole. The systemic availability (bioavailability) of a single oral dose of the drug is about 40%. With repeated administration in a once-daily regimen, bioavailability increases to 60%.
The apparent volume of distribution in healthy volunteers is about 0.3 l/kg body weight. Omeprazole is 97% bound to plasma proteins.
Omeprazole is completely metabolized by the cytochrome P450 (CYP) system, mainly with the participation of CYP2C19, which is responsible for the formation of hydroxyomeprazole as the main metabolite of omeprazole in blood plasma. The sulfone derivative of omeprazole is formed with the participation of another isoform, namely CYP3A4. Due to the high affinity of omeprazole for CYP2C19, competitive inhibition of the metabolism of other substrates by this isoform is possible. However, the affinity of omeprazole for CYP3A4 is low, so omeprazole cannot inhibit the metabolism of other CYP3A4 substrates. However, omeprazole does not inhibit the main enzymes of the cytochrome P450 system. The half-life of omeprazole from blood plasma is less than 1 hour after both single and multiple doses. Omeprazole is completely eliminated from blood plasma between doses. When taken once daily, there is no tendency for accumulation of the drug. About 80% of the dose of omeprazole that enters the body is excreted in the urine as metabolites. The rest is excreted in the feces due to bile secretion.
With repeated administration, the area under the concentration-time curve for omeprazole increases. This increase is dose-dependent and the relationship is not linear. The time and dose dependence is a consequence of a decrease in first-pass metabolism and systemic clearance, presumably due to inhibition of CYP2C19 by omeprazole and/or its metabolites (e.g. the sulfone). Omeprazole metabolites do not affect gastric acid secretion.
Domperidone.
After oral administration on an empty stomach, domperidone is rapidly absorbed. Peak plasma concentrations are reached within 30-60 minutes. The low absolute bioavailability of domperidone (about 15%) after oral administration is due to significant presystemic metabolism in the intestinal wall and liver. Although the bioavailability of domperidone increases in healthy volunteers when taken with food, patients with gastrointestinal complaints should take the drug 15-30 minutes before meals. Reduced acidity of gastric contents impairs the absorption of domperidone. The bioavailability of the drug after oral administration is reduced by prior administration of cimetidine and sodium bicarbonate. If domperidone is taken after meals, the time of maximum absorption is somewhat delayed, and the area under the "concentration-time" curve increases.
Domperidone is rapidly and extensively metabolized in the liver by hydroxylation and
N- dealkylation.
31% and 66% of the oral dose are excreted in the urine and feces, respectively. A small portion of the drug is excreted unchanged (10% in the feces and 1% in the urine). The plasma half-life after a single dose in healthy volunteers is 7-9 hours. This time is prolonged in patients with severe renal failure.
Indication
Functional dyspepsia, delayed gastric emptying and gastroparesis, reflux esophagitis, gastric and duodenal ulcers; in Helicobacter pylori eradication regimens in the presence of gastroesophageal reflux.
Contraindication
Hypersensitivity to domperidone, omeprazole, substituted benzimidazoles or to any of the other ingredients of the product. Prolactin-secreting pituitary tumor (prolactinoma). Gastrointestinal bleeding, mechanical intestinal obstruction, perforation of the stomach or intestines. Severe or moderate hepatic and/or renal dysfunction. Patients with known prolongation of cardiac conduction intervals, particularly QTc, patients with significant electrolyte imbalance or underlying heart disease such as congestive heart failure (see section "Special warnings and precautions for use"). Hepatic failure.
Concomitant use of ketoconazole, erythromycin or other potent CYP3A4 inhibitors, medicinal products that prolong the QT interval such as fluconazole, itraconazole, oral ketoconazole, posaconazole, ritonavir, saquinavir, telaprevir, voriconazole, clarithromycin, amiodarone, erythromycin, telithromycin (see sections “Special precautions” and “Interaction with other medicinal products and other types of interactions”). Concomitant use with nelfinavir and atazanavir.
Interaction with other medicinal products and other types of interactions
Domperidone.
Anticholinergic drugs may neutralize the antidyspeptic effect of domperidone.
Antacids and antisecretory drugs should not be taken simultaneously with domperidone, as they reduce its bioavailability after oral administration.
The main metabolic pathway of domperidone occurs with the participation of the CYP3A4 isoenzyme of the cytochrome P450 system, therefore, with the simultaneous use of domperidone and drugs that significantly inhibit this isoenzyme, an increase in the level of domperidone in the blood plasma is possible.
Concomitant use with ketoconazole, erythromycin or other potential CYP3A4 inhibitors may lead to prolongation of the QT interval.
With simultaneous use of domperidone at a dose of 10 mg 4 times a day and ketoconazole at a dose of 200 mg twice a day, an average prolongation of the QT interval by 9.8 msec (from 1.2 to 17.5 msec individually) is observed. With simultaneous use of domperidone at a dose of 10 mg 4 times a day and erythromycin at a dose of 500 mg three times a day, an average prolongation of the QT interval by 9.9 msec (from 1.6 to 14.3 msec individually) is observed. At steady state, with such an interaction, Cmax and area under the concentration-time curve for domperidone increase approximately threefold. In these studies, monotherapy with domperidone at a dose of 10 mg four times a day led to an increase in the QT interval by 1.6 msec (interaction study with ketoconazole) and by 2.5 msec (interaction study with erythromycin). Ketoconazole monotherapy (200 mg twice daily) resulted in an increase in the QT interval by 3.8 msec, and erythromycin monotherapy (500 mg three times daily) by 4.9 msec.
Clinically significant changes in the QT interval have been observed when domperidone was used concomitantly with potent CYP3A4 inhibitors that can prolong the QT interval. Therefore, the concomitant use of domperidone with certain drugs is contraindicated (see section "Contraindications").
Concomitant use of the following drugs with domperidone is contraindicated.
All drugs that prolong the QT interval:
Class IA antiarrhythmic drugs (e.g., disopyramide, quinidine, hydroquinidine);
Class III antiarrhythmic drugs (e.g. amiodarone, dofetilide, dronedarone, ibutilide, sotalol);
some neuroleptic drugs (e.g. haloperidol, pimozide, sertindole);
some antidepressants (e.g. citalopram, escitalopram);
certain antibiotics (e.g., levofloxacin, moxifloxacin, erythromycin, spiramycin);
some antifungal drugs (e.g. pentamidine);
certain antimalarial drugs (e.g., halofantrine, lumefantrine);
certain gastrointestinal medications (e.g., cisapride, dolasetron, prucalopride);
some antihistamines (e.g. mecitazine, mizolastine);
some drugs used in cancer (e.g. toremifene, vandetanib, vincamine);
some other drugs (e.g. bepridil, methadone, diphemanil).
Strong CYP3A4 inhibitors with which domperidone is not recommended:
azole antifungals such as fluconazole*, itraconazole*, ketoconazole* and voriconazole*;
macrolide antibiotics such as clarithromycin* and erythromycin;
protease inhibitors*;
HIV protease inhibitors such as amprenavir, atazanavir, fosamprenavir, indinavir, nelfinavir, ritonavir, and saquinavir;
calcium antagonists such as diltiazem and verapamil;
amiodarone*;
amrepitant;
nefazodone;
telithromycin*
(*prolong the QTc interval).
Use with caution with drugs that cause bradycardia and hypokalemia, as well as with the following macrolides that may cause QT prolongation: azithromycin and roxithromycin (clarithromycin is contraindicated as it is a potent CYP3A4 inhibitor).
Domperidone should be used with caution when used concomitantly with potent CYP3A4 inhibitors that have not been shown to prolong the QT interval, such as indinavir, and patients should be closely monitored for signs or symptoms of adverse reactions.
Domperidone can be combined with:
- neuroleptics, the effect of which it enhances;
- dopaminergic agonists (bromocriptine, L-dopa), whose undesirable peripheral effects, such as digestive disorders, nausea, vomiting, it suppresses without neutralizing the basic properties.
Omeprazole.
The decrease in gastric acidity during the use of omeprazole may alter the absorption of drugs for which this process is pH-dependent. When omeprazole is used concomitantly with nelfinavir, atazanavir, the concentration of the latter in the blood plasma decreases. The combined use of omeprazole with nelfinavir is contraindicated. The use of omeprazole at a dose of 40 mg once a day reduces the content of nelfinavir by an average of 40%, and its pharmacologically active metabolite M8 - by 75-90%. Another mechanism of interaction is possible through CYP2C19.
The concomitant use of omeprazole and atazanavir is not recommended. When omeprazole 40 mg once daily was co-administered with atazanavir 300 mg/ritonavir 100 mg in healthy volunteers, the exposure to atazanavir was reduced by 75%. Increasing the dose of atazanavir to 400 mg did not compensate for this effect of omeprazole. When omeprazole 20 mg once daily was co-administered with atazanavir 400 mg/ritonavir 100 mg in healthy volunteers, the exposure to atazanavir was reduced by approximately 30%.
Increased serum levels of other antiretroviral agents, such as saquinavir, have been reported. There are also other antiretroviral agents whose serum levels have been unchanged when co-administered with omeprazole.
Co-administration of omeprazole 20 mg once daily with digoxin in healthy volunteers increased the bioavailability of digoxin by 10%. Although no digoxin toxicity has been reported in such cases, caution should be exercised when administering high doses of omeprazole with digoxin in the elderly.
In a crossover clinical study, co-administration of clopidogrel (300 mg loading dose followed by 75 mg daily) with omeprazole (80 mg co-administered) for 5 days reduced the exposure of the active metabolite of clopidogrel by 46% (day 1) and 42% (day 2). Platelet aggregation was reduced by 47% after 24 hours and by 30% on day 5. In another clinical study, it was shown that taking clopidogrel and omeprazole at different times did not prevent this interaction, which is likely due to inhibition of CYP2C19 by omeprazole.
The use of omeprazole significantly reduces the absorption of posaconazole, erlotinib, ketoconazole and itraconazole, which may reduce the clinical efficacy of these drugs. Concomitant administration of the drug with posaconazole and erlotinib should be avoided.
Omeprazole inhibits CYP2C19, the main omeprazole-metabolizing enzyme. Therefore, the metabolism of concomitant drugs that are also metabolized by CYP2C19, such as diazepam, phenytoin, warfarin (R-warfarin) or other vitamin K antagonists and cilostazol, may be slowed down. Monitoring of patients taking phenytoin is recommended, and a reduction in the phenytoin dose may also be necessary. However, concomitant administration of 20 mg omeprazole per day did not change the blood concentration of phenytoin in patients taking this drug for a long time. Monitoring of MHC is recommended in patients taking warfarin or other vitamin K antagonists; a reduction in the dose of warfarin (or other vitamin K antagonist) may be necessary. However, concomitant administration of 20 mg omeprazole per day did not change the coagulation time in patients taking warfarin for a long time. Omeprazole is also partially metabolized by CYP3A4, but does not inhibit this enzyme. Thus, omeprazole does not affect the metabolism of drugs metabolized by CYP3A4, such as cyclosporine, lidocaine, quinidine, estradiol, erythromycin and budesonide. Increased methotrexate levels have been reported in some patients when administered concomitantly with proton pump inhibitors. If high doses of methotrexate are necessary, temporary withdrawal of omeprazole should be considered.
Concomitant use of omeprazole with tacrolimus may lead to increased serum concentrations of tacrolimus. It is recommended to monitor tacrolimus plasma concentrations at the beginning or after discontinuation of omeprazole treatment.
Drugs that induce CYP2C19, CYP3A4, or both enzymes (such as rifampicin, St. John's wort) may lead to decreased serum levels of omeprazole by accelerating its metabolism.
Other active ingredients.
Ampicillin: Omeprazole causes significant and prolonged inhibition of gastric acid secretion. Concomitant administration of ampicillin and omeprazole may impair the absorption of the antibiotic, leading to a decrease in its bioavailability.
Iron: Omeprazole administration results in significant and prolonged inhibition of gastric acid secretion, which may lead to reduced iron absorption in the gastrointestinal tract.
Carbamazepine: Omeprazole has been reported to increase the half-life, area under the concentration-time curve (AUC) and decrease the clearance of carbamazepine after a single dose of carbamazepine.
Cyanocobalamin: Omeprazole may reduce the absorption of vitamin B12 when taken orally.
Cyclosporine: The effect of omeprazole on cyclosporine concentrations has not been fully established. Controlled studies have not shown significant changes or decreases in cyclosporine plasma concentrations. Cases of increased and decreased cyclosporine levels have been reported. Therefore, when treating patients with cyclosporine and omeprazole simultaneously, it is necessary to monitor the level of cyclosporine in the blood plasma.
Disulfiram: Concomitant use with omeprazole may lead to increased serum concentrations of disulfiram with manifestations of disulfiram toxicity such as confusion, disorientation and changes in mental status.
Grapefruit juice: Concomitant administration of grapefruit juice and omeprazole 20 mg reduces the formation of omeprazole sulfone mediated by cytochrome P450 3A4, but does not inhibit the formation of 5-hydroxyomeprazole mediated by cytochrome P450 2C19. The clinical significance of this interaction has not been established.
Cranberry juice: when taken with omeprazole, causes a significant decrease in gastric pH. Regular consumption of cranberry juice during treatment with proton pump inhibitors may reduce their effectiveness. Occasional consumption of cranberry juice is unlikely to have a clinical effect on gastric acidity, but caution is advised. It is currently unknown whether dietary supplements containing cranberry extracts have the same effect on gastric acidity, but caution is advised.
The absorption of omeprazole may be slowed by food, so the drug should be administered on an empty stomach.
Ticlopidine: Ticlopidine inhibits the metabolism of omeprazole in individuals who have been identified as extensive metabolizers of cytochrome P450 2C19 (CYP2C19).
The mechanisms of interaction are unknown.
Co-administration of omeprazole with saquinavir/ritonavir resulted in an increase in plasma concentrations of saquinavir of approximately 70%, which is associated with good tolerability in HIV-infected patients.
Application features
Antacids or antisecretory drugs when used concomitantly with domperidone should be taken after meals, but should not be taken simultaneously with domperidone. Patients who experience persistent discomfort after meals and who have to take domperidone continuously for more than 2 weeks should consult a doctor. Patients whose nausea and vomiting last more than 48 hours should consult a doctor.
In interaction studies with oral ketoconazole, QT prolongation was observed. Although the significance of this study is not clearly established, alternative treatment should be considered if antifungal therapy with ketoconazole is indicated (see section 4.5).
Domperidone should be used with caution in patients with risk factors for QT prolongation, including hypokalemia, severe hypomagnesemia, organic heart disease, and in patients with mild hepatic and/or renal impairment.
Renal impairment. The elimination half-life of domperidone is prolonged in severe renal impairment. With prolonged use, the dosing frequency of domperidone should be reduced to once or twice daily, depending on the severity of the impairment. A dose reduction may also be required.
If peptic ulcer is present or suspected, or if any of the following symptoms are present: significant unexplained weight loss, vomiting, dysphagia, haematemesis or melena, malignancy should be excluded, as treatment with omeprazole may mask its symptoms and delay diagnosis.
If the patient has been diagnosed with an intolerance to some sugars, contact your doctor before taking this medicinal product.
The drug contains lactose and sucrose, so the drug should not be used in patients with lactose intolerance, galactosemia, and glucose/galactose, fructose, and sucrose-isomaltose malabsorption.
Domperidone may cause an increase in prolactin levels, causing galactorrhea in women and gynecomastia in men.
In patients with pheochromocytoma, hypertensive crisis may occur when using domperidone.
Cardiovascular Effects: Domperidone has been associated with QT prolongation on the ECG. Very rare cases of QT prolongation and ventricular fibrillation have been reported in post-marketing experience in patients taking domperidone. These reports included patients with other predisposing risk factors, electrolyte abnormalities, and concomitant medications that may have been contributing factors.
A study was conducted in healthy subjects in accordance with ICH-E14 guidelines to investigate the QT interval. The QT prolongation observed in the study with domperidone, at the recommended dosage regimen at the usual therapeutic doses (10 or 20 mg 4 times a day), is not clinically relevant.
Due to the increased risk of ventricular arrhythmias, domperidone is contraindicated in patients with prolongation of cardiac conduction intervals, particularly QTc, in patients with significant electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) or bradycardia, or in patients with underlying cardiac disease such as congestive heart failure. Electrolyte imbalance (hypokalemia, hyperkalemia, hypomagnesemia) and bradycardia are known to be conditions that increase the proarrhythmic risk.
If signs or symptoms that may be associated with cardiac arrhythmia appear, domperidone should be discontinued and the patient should consult a doctor immediately.
The following information should be considered regarding the risk of cardiovascular complications caused by medicines containing domperidone:
Some epidemiologists have used doses of the drug greater than 30 mg per day.
Domperidone should be prescribed to adults and children at the lowest effective dose.
The risk-benefit ratio of domperidone remains favorable.
Concomitant use of atazanavir with proton pump inhibitors is not recommended. If the combination of atazanavir with a proton pump inhibitor cannot be avoided, close clinical monitoring (e.g. viral load) is recommended in conjunction with an increase in the dose of atazanavir to 400 mg per 100 mg of ritonavir; the dose of omeprazole should not exceed 20 mg.
Reduced acid secretion in the stomach, which may result from the action of proton pump inhibitors or other acid-inhibiting agents, leads to an increase in the number of bacteria present in the gastrointestinal tract, which, in turn, leads to a slightly increased risk of developing intestinal infections caused by bacteria such as Salmonella and Campylobacter.
Omeprazole is an inhibitor of CYP2C19. When initiating or ending treatment with omeprazole, the potential for interactions with drugs metabolized by CYP2C19, such as clopidogrel, should be considered. The clinical significance of this interaction remains unclear. As a precautionary measure, concomitant use of omeprazole and clopidogrel should be avoided.
During treatment with antisecretory drugs, the concentration of gastrin in the blood plasma increases as a result of a decrease in hydrochloric acid secretion. As a result of a decrease in hydrochloric acid secretion, the level of chromogranin A (CgA) increases. An increase in the concentration of CgA may affect the results of studies for the detection of neuroendocrine tumors. To prevent such an effect, it is necessary to stop taking the proton pump inhibitor 5 days before determining the level of CgA.
Omeprazole may reduce the absorption of cyanocobalamin. This should be borne in mind when prescribing the drug for a long time to patients with reduced vitamin B12 levels in the body or with impaired absorption of vitamin B12 from the gastrointestinal tract.
Omeprazole, like other acid-inhibiting substances, may reduce the absorption of vitamin B12 (cyanocobalamin) due to hypo- or achlorhydria. This should be taken into account when treating patients with vitamin B12 deficiency or at risk of reduced vitamin B12 absorption during long-term therapy. In individual cases, monitoring of vitamin B12 plasma levels may be appropriate.
Use of proton pump inhibitors, especially at high doses and over long periods (>1 year), may slightly increase the risk of hip, wrist, and spine fractures, mainly in elderly patients or those with other known risk factors. Observational studies suggest that proton pump inhibitors may increase the risk of fractures by an overall 10-40%.
In some cases, this is due to the presence of other risk factors in the patient. Patients at risk of osteoporosis should be provided with appropriate treatment and adequate intake of vitamin D and calcium.
The use of proton pump inhibitors may be associated with an increased risk of C. difficile-associated diarrhea.
In patients requiring long-term use of proton pump inhibitors and in patients concomitantly taking digoxin or other drugs that may cause hypomagnesemia (e.g. diuretics), magnesium levels should be checked before starting treatment and periodically during treatment.
In some cases, treatment of chronic diseases in children may require longer-term use of the drug, although this is not recommended.
The use of proton pump inhibitors can sometimes cause the appearance of subacute cutaneous lupus erythematosus. If skin manifestations appear, especially in areas exposed to sunlight and accompanied by arthralgia, you should immediately consult a doctor and consider stopping omeprazole. A history of subacute cutaneous lupus erythematosus that developed after the use of proton pump inhibitors may increase the risk of subacute cutaneous lupus erythematosus with the use of other proton pump inhibitors.
Use during pregnancy or breastfeeding
It should not be used in pregnant women. If necessary, breastfeeding should be discontinued.
The ability to influence the reaction speed when driving or working with other mechanisms
During treatment with the drug, special care should be taken when driving vehicles and/or working with potentially dangerous mechanisms.
Method of administration and doses
Capsules should be taken whole, without opening or chewing. The recommended dose depends on the course of the disease and is set individually by the doctor. The average recommended dose for adults and children over 12 years of age is 1 capsule 2-3 times a day 30 minutes before meals, washed down with a glass of water. If necessary, the dose may be increased by the doctor to 2 capsules 2 times a day. The course of treatment is 4-8 weeks.
In eradication regimens, 2 capsules 2 times a day in combination with antibacterial agents.
Children
The drug should be used to treat children aged 12 years and over and weighing at least 35 kg.
Overdose
Overdose due to the action of domperidone.
Symptoms: agitation, impaired consciousness, convulsions, disorientation, drowsiness, extrapyramidal reactions.
Treatment: gastric lavage, administration of activated charcoal, anticholinergics to eliminate extrapyramidal disorders. In case of extrapyramidal reactions, use anticholinergic drugs and drugs for the treatment of parkinsonism.
Overdose due to the action of omeprazole.
Symptoms: dry mouth, nausea, vomiting, dizziness, profuse sweating, abdominal pain, flatulence, diarrhea, flushing, headache, blurred vision, tachycardia, apathy, depression, drowsiness, confusion. All symptoms are transient. The elimination rate remains unchanged regardless of the dose (first-order kinetics).
Treatment is symptomatic. There is no specific antidote. A significant part of omeprazole binds to plasma proteins, so hemodialysis is ineffective.
Side effects
Provided that the dosage and duration of treatment recommendations are followed, domperidone is usually well tolerated and adverse events occur infrequently.
Adverse reactions, information about which is given below, are classified by organ system and by frequency of occurrence: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10000 and <1/1000), very rare (<1/10000) and those whose frequency is unknown.
Immune system disorders: Rare: angioedema; hypersensitivity reactions including anaphylaxis, anaphylactic shock; fever, bronchospasm, abdominal swelling. Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis.
Skin and subcutaneous tissue disorders: Uncommon: skin rash, pruritus, dermatitis, urticaria. Rare: alopecia, photosensitivity, purpura and/or petechiae (sometimes with recurrence after re-administration), skin inflammation, dry skin, hyperhidrosis. Very rare: erythema multiforme, subacute cutaneous lupus erythematosus, angioedema.
Psychiatric disorders: Uncommon: anxiety. Rare: agitation, confusion, depression. Very rare: aggression, hallucinations, nervousness, irritability, decreased or absent libido.
Nervous system disorders: Very rare: headache, dizziness, paresthesia, drowsiness, taste disturbance, loss of consciousness, general weakness, insomnia, lethargy, anxiety, paresthesia, agitation, reversible confusion, aggressiveness, depression, nervousness, tremor, apathy, hallucinations, hemifacial dysesthesia. Frequency unknown: convulsions, extrapyramidal disorders, irritability, agitation, akathisia, systemic dizziness (vertigo).
Cardiovascular system: Very rare: ventricular arrhythmias, peripheral edema, palpitations, heart rate and rhythm disturbances. Frequency unknown: QT prolongation, torsade de pointes ventricular arrhythmias, sudden cardiac death, chest pain or angina pectoris, tachycardia, bradycardia, increased blood pressure, peripheral edema.
On the part of the organs of vision. Rare: blurred vision. Frequency unknown: oculogyric crisis.
Respiratory system: Rare: bronchospasm.
Gastrointestinal disorders: Common: abdominal pain, constipation, flatulence. Rare: gastrointestinal disorders including abdominal pain, acid regurgitation, change in appetite, nausea, heartburn, constipation. Very rare: dry mouth, transient intestinal spasms, diarrhoea, stomatitis, gastrointestinal candidiasis, loss of appetite, taste perversion. Frequency not known: intestinal colic, taste perversion, vomiting, microscopic colitis, pancreatitis (sometimes fatal), discolouration of stools, atrophy of the mucous membrane of the tongue, thirst. Fundic gland polyps have been reported rarely during treatment with omeprazole. These polyps are benign and may disappear after discontinuation of treatment. Gastric and duodenal carcinoids have been reported in patients with Zollinger-Ellison syndrome on long-term treatment with omeprazole. These changes are believed to be a manifestation of an underlying disease known to be associated with such tumors.
Musculoskeletal disorders: Rare: arthralgia, myalgia. Very rare: muscular weakness. Frequency unknown: leg pain, fractures of the hip, wrist or spine.
Hepatobiliary disorders: Rare: increased liver enzymes, hepatitis with or without jaundice. Very rare: hepatic failure, encephalopathy in patients with pre-existing liver disease.
Renal and urinary disorders: Rare: interstitial nephritis (sometimes with recurrence after resumption of treatment), urinary tract infection, micropyuria, increased serum creatinine, proteinuria, hematuria, glycosuria, testicular pain. Very rare: urinary retention, dysuria, frequent urination.
Reproductive system and breast disorders: Rare: galactorrhea, breast enlargement/gynecomastia, breast tenderness, breast discharge, breast pain, amenorrhea, increased prolactin levels, irregular menstrual cycle.
Metabolic disorders: Rare: hyponatremia, increased prolactin levels. Very rare: hypomagnesemia which may lead to hypokalemia; severe hypomagnesemia which may lead to hypocalcemia.
Blood system disorders: Rare: leukopenia, thrombocytopenia. Very rare: agranulocytosis (sometimes fatal), pancytopenia, neutropenia, anemia, leukocytosis, hemolytic anemia.
Laboratory parameters: Very rare: increased ALT, AST and cholesterol Rare: increased serum prolactin Very rare: abnormal liver function tests.
Since the pituitary gland is located outside the blood-brain barrier, domperidone may cause an increase in prolactin levels. In rare cases, this hyperprolactinemia may lead to neuroendocrine side effects such as galactorrhea, gynecomastia, and amenorrhea.
Other disorders. Rare: asthenia, malaise, peripheral edema. Rare: increased sweating, fever, impotence. Frequency unknown: conjunctivitis, stomatitis, lethargy.
During post-marketing use of domperidone, no differences in the safety profile of domperidone in adults and children were noted, with the exception of extrapyramidal disorders and other phenomena, seizures and agitation related to the central nervous system, which were observed mainly in children.
Expiration date
2 years.
Storage conditions
