Retch, tablets 50 mg 40 pcs

Gastrointestinal motility stimulator – acetylcholine release stimulator.

Pharmacokinetics

Intake

It is rapidly and almost completely absorbed in the gastrointestinal tract. Its relative bioavailability is 60%, which is due to metabolism during first passage through the liver.

The maximum plasma concentration (Cmax) of 0.28 mcg/ml, after 50 mg of the drug, is reached in 0.5-0.75 h

In repeated oral administration of the drug at a dose of 50-200 mg three times daily for 7 days, the pharmacokinetics is linear and cumulation is minimal.

Distribution

Binding to plasma proteins is 96%, mostly to albumin. Binding to alpha1-acid glycoprotein is less than 15%.

It is actively distributed in the tissues (volume of distribution 6.1 l/kg) and found in high concentrations in the kidneys, small intestine, liver, adrenal glands and stomach. In therapeutic doses it slightly penetrates into brain and spinal cord, into breast milk.

Metabolism

Metabolized in the liver. Three metabolites have been identified, one of which has negligible activity that has no pharmacological significance (approximately 2-3% of that of itoprid). The primary metabolite in humans is N-oxide, which is formed by oxidation of the quaternary amino-N-dimethyl group.

It is metabolized under the action of flavin-dependent monooxygenase (FMO3). The number and efficiency of human isoenzymes may vary depending on the genetic polymorphism, which in rare cases leads to the development of an autosomal recessive condition known as trimethylaminuria (fish odor syndrome).

In patients with trimethylaminuria, the half-life of the drug is prolonged.

The drug has no inhibitory or inducing effect on CYP2C19 and CYP2E1. The use of etopride has no effect on the activity of uridine diphosphate glucuronidyltransferase.

Itopride and its metabolites are excreted by the kidneys. Renal excretion of itopride and its N-oxide after a single oral administration of the drug in therapeutic doses in healthy subjects was 3.7% and 75.4%, respectively.

The half-life of the drug (T1/2) is 6 hours.

Pharmacodynamics

It increases motility of gastrointestinal tract (GIT) due to antagonism of D2-dopamine receptors and inhibition of acetylcholinesterase. It activates the release of acetylcholine and inhibits its degradation.

It has antiemetic effect due to interaction with D2-receptors located in the trigger zone. Causes dose-dependent suppression of apomorphine-induced vomiting.

Activates propulsive gastric motility through antagonism by D2-receptors and dose-dependent inhibition of acetylcholinesterase activity.

The action of the drug in patients with functional dyspepsia leads to a decrease in the severity of symptoms (overall patient evaluation, postprandial abdominal heaviness, early satiety).

The use of itopride in patients with diabetic gastroparesis promoted faster evacuation of liquid and solid food from the stomach.

In patients with gastroesophageal reflux disease (GERD), itopride reduces the number of transient relaxations of the lower esophageal sphincter and reduces the duration of time with high esophageal acidity (pH

It has a specific effect on the smooth muscles of the gastrointestinal tract, accelerating gastric transit and improving gastric emptying. It does not affect serum concentrations of gastrin.

Indications

Active ingredient

Composition

1 tablet:

How to take, the dosage

In adults, 1 tablet of Retch 50 mg 3 times daily before meals is usually prescribed orally.

The recommended daily dose is 3 tablets (150 mg).

The above dose may be reduced based on the age and symptoms of the patient.

If the drug is not taken on time, it should be taken at regular intervals thereafter. It is not recommended to take a double dose to make up for a missed dose.

In clinical trials, the duration of treatment with etopride was up to 8 weeks.

Interaction

No interactions have been found when taking itopride concomitantly with warfarin, diazepam, diclofenac, ticlopidine, nifedipine and nicardipine.

No metabolic interaction at the level of CYP450 isoenzymes is expected, because metabolism of itoprid is mainly via flavin monooxygenase.

Itopride increases gastric motility, which may affect absorption of the drugs when used together orally. Particular caution should be exercised when taking drugs with a narrow therapeutic index, drugs with prolonged release of the active substance or enteric-coated drugs.

The anti-ulcer drugs such as cimetidine, ranitidine, teprenone and cetraxate do not affect the prokinetic efficacy of itopride.

M-cholinoblockers decrease the efficacy of itopride.

The cholinergic effects of itopride may increase with concomitant use of M-cholinomimetics as well as cholinesterase inhibitors.

Special Instructions

Itopride enhances the effects of acetylcholine and may cause cholinergic adverse reactions.

Patients with impaired hepatic or renal function should be closely monitored by a physician, and if necessary, the dose of the drug should be reduced or therapy with the drug should be discontinued.

If symptoms of galactorrhea and gynecomastia occur, treatment should be discontinued or stopped completely.

The effect on the ability to drive and operate machinery

There have been no studies regarding the effect of etopride on the ability to drive and operate machinery.

We should, however, during the period of the drug treatment be careful when performing potentially dangerous activities requiring increased concentration and quick psychomotor reactions (driving vehicles, operating moving mechanisms, work of dispatcher and operator), since the use of the drug may cause dizziness.

Contraindications

Hypersensitivity to itopride or any excipient of the drug; patients with gastrointestinal bleeding, mechanical obstruction or perforation; childhood age (below 16 years); pregnancy and lactation; lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Patients with caution in whom the development of cholinergic adverse reactions (associated with increased acetylcholine action during drug therapy) may aggravate the underlying disease; patients with hepatic and renal dysfunction; patients of advanced age.

Side effects

World Health Organization (WHO) frequency classification of adverse reactions: very common (≥ 1/10), common (≥ 1/100 and

Blood and lymphatic system disorders: infrequent – leukopenia, unknown frequency – thrombocytopenia.

Immune system disorders: rare – skin hyperemia, skin itching, rash, frequency unknown – anaphylactoid reactions.

Endocrine system disorders: infrequent – hyperprolactinemia, frequency unknown – gynecomastia.

Nervous system disorders: infrequent – dizziness, headache, sleep disturbance, irritability, frequency is unknown – tremor.

Gastrointestinal disorders: infrequent – diarrhea, constipation, abdominal pain, increased salivation, frequency unknown – nausea, jaundice.

Muscular and connective tissue disorders: infrequent – pain in the chest or back.

Impact on the results of laboratory and instrumental studies: infrequent – increase in creatinine and urea nitrogen in the blood (BUN), frequency is unknown – increase in aspartate aminotransferase (ACT), alanine aminotransferase (ALT), gammaglutamyl transpeptidase, alkaline phosphatase and bilirubin levels.

Others: infrequent – fatigue.

Overdose

In human cases of overdose have not been described.

In case of overdose gastric lavage and symptomatic therapy are indicated.

Pregnancy use

Pregnancy

There are insufficient data on the use of itopride hydrochloride in pregnant women. Use during pregnancy is possible only if there is no alternative therapy available and the potential benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding

There is a potential risk of adverse reactions in the infant; there are also data on excretion of itopride with milk in rats. If administration during lactation is necessary, breastfeeding should be discontinued.

Similarities