Ganaton, 50 mg 70 pcs.

Pharmacotherapeutic group – gastrointestinal motility stimulator – acetylcholine release stimulator.

The ATC code is A03FA.

Pharmacological properties

The mechanism of action

Itopride hydrochloride increases gastrointestinal motility by antagonizing D2-dopamine receptors and inhibiting acetylcholinesterase. Itopride activates the release of acetylcholine and inhibits its degradation.

Pharmacodynamics

Itopride hydrochloride also gives an antiemetic effect due to interaction with D2 receptors located in the trigger zone. Itopride caused dose-dependent suppression of vomiting induced by apomorphine.

Itopride hydrochloride activates gastric propulsive motility through antagonism of D2 receptors and dose-dependent inhibition of acetylcholinesterase activity.

Itopride hydrochloride has a specific effect on the upper gastrointestinal tract, accelerating gastric transit and improving gastric emptying.

Itopride hydrochloride has no effect on serum levels of gastrin.

Pharmacokinetics

Intopride hydrochloride is rapidly and almost completely absorbed in the GI tract. Its relative bioavailability is 60%, which is due to metabolism during first passage through the liver. Food has no effect on bioavailability. The maximum plasma concentration (Cmax) of 0.28 µg/ml is reached 0.5-0.75 h after administration of 50 mg of itopride hydrochloride.

Recurrent oral administration of itopride hydrochloride at a dose of 50-200 mg three times daily for 7 days showed linear pharmacokinetics of the drug and its metabolites, and cumulation was minimal.

Distribution

Itopride hydrochloride is 96% bound to plasma proteins, mainly to albumin. Binding to alpha1-acid glycoprotein is less than 15% of total binding.

Itoprid is actively distributed in the tissues (volume of distribution 6.1 l/kg) and is found in high concentrations in the kidneys, small intestine, liver, adrenal glands and stomach. Penetration into the brain and spinal cord is minimal. Itoprid penetrates into breast milk.

Metabolism

Itoprid undergoes active biotransformation in the liver in humans. Three metabolites have been identified, only one of which exhibits little activity that has no pharmacological significance (approximately 2-3% of that of itopride). The primary metabolite in humans is N-oxide, which is formed by oxidation of the quaternary amino-N-dimethyl group.

Itoprid is metabolized by the action of flavin-dependent monooxygenase (FMO3). The number and efficiency of FMO isoenzymes in humans can vary depending on the genetic polymorphism, which in rare cases leads to the development of an autosomal recessive condition known as trimethylaminuria (fish-smell syndrome). In patients with trimethylaminuria, the half-life of ithopride is prolonged.

According to in vivo pharmacokinetic studies, itoprid has no inhibitory or inducing effect on CYP2C19 and CYP2E1. Therapy with itopride has no effect on CYP or uridine diphosphate glucuronidyltransferase activity.

Itopride hydrochloride and its metabolites are excreted mainly in the urine. Renal excretion of ithopride 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 terminal period of semi-elimination of itopride hydrochloride is about 6 hours.

Indications

Itopride hydrochloride is used for the symptomatic treatment of functional non-ulcer dyspepsia (chronic gastritis), in particular relief of bloating, rapid satiety, pain or discomfort in the upper abdomen, anorexia, heartburn, nausea and vomiting.

Pharmacological effect

Pharmacotherapeutic group – gastrointestinal motility stimulator – acetylcholine release stimulator.

ATX code – A03FA.

Pharmacological properties

Mechanism of action

Itopride hydrochloride enhances gastrointestinal motility due to antagonism of D2-dopamine receptors and inhibition of acetylcholinesterase. Itopride activates the release of acetylcholine and inhibits its destruction.

Pharmacodynamics

Itopride hydrochloride also provides an antiemetic effect due to interaction with D2 receptors located in the trigger zone. Itopride caused a dose-dependent suppression of apomorphine-induced vomiting.

Itopride hydrochloride activates propulsive gastric motility through antagonism of D2 receptors and dose-dependent inhibition of acetylcholinesterase activity.

Itopride hydrochloride has a specific effect on the upper gastrointestinal tract, accelerates gastric transit and improves gastric emptying.

Itopride hydrochloride does not affect serum gastrin levels.

Pharmacokinetics

Suction

Itopride hydrochloride is quickly and almost completely absorbed from the gastrointestinal tract. Its relative bioavailability is 60%, which is associated with first-pass metabolism through the liver. Food has no effect on bioavailability. The maximum plasma concentration (Cmax) of 0.28 mcg/ml is achieved 0.5-0.75 hours after taking 50 mg of itopride hydrochloride.

When itopride hydrochloride was repeatedly taken orally at a dose of 50-200 mg three times a day for 7 days, the pharmacokinetics of the drug and its metabolites were linear, and accumulation was minimal.

Distribution

Itopride hydrochloride is 96% bound to plasma proteins, mainly albumin. Binding to alpha1-acid glycoprotein accounts for less than 15% of total binding.

Itopride is actively distributed into tissue (volume of distribution 6.1 l/kg) and is found in high concentrations in the kidneys, small intestine, liver, adrenal glands and stomach. Penetration into the brain and spinal cord is minimal. Itopride passes into breast milk.

Metabolism

Itopride undergoes active biotransformation in the human liver. 3 metabolites have been identified, only one of which exhibits small activity that has no pharmacological significance (approximately 2-3% of that of itopride). The primary metabolite in humans is N-oxide, which is formed as a result of oxidation of the quaternary amino-N-dimethyl group.

Itopride is metabolized by flavin-dependent monooxygenase (FMO3). The amount and effectiveness of FMO isoenzymes in humans may vary due to genetic polymorphisms, which in rare cases lead to the development of an autosomal recessive condition known as trimethylaminuria (fishy odor syndrome). In patients with trimethylaminuria, the half-life of itopride increases.

According to in vivo pharmacokinetic studies, itopride does not have an inhibitory or inducing effect on CYP2C19 and CYP2E1. Itopride therapy does not affect CYP or uridine diphosphate glucuronyl transferase activity.

Removal

Itopride hydrochloride and its metabolites are excreted mainly in the urine. Renal excretion of itopride and its N-oxide after a single oral dose of the drug in therapeutic doses in healthy people was 3.7 and 75.4%, respectively. The terminal half-life of itopride hydrochloride is approximately 6 hours.

Special instructions

Due to the enhancement of the action of acetylcholine by itopride, the drug should be prescribed with caution due to the possible development of cholinergic adverse reactions in patients for whom their occurrence may aggravate the course of the underlying disease.

Active ingredient

Itopride

Composition

1 tablet contains:

Active ingredient:

itopride hydrochloride – 50 mg;

Excipients:

lactose – 34.975 mg (including excess due to weight loss during production – 2.93%),

corn starch – 15 mg,

carmellose – 20 mg,

anhydrous silicic acid – 4 mg,

magnesium stearate – 1 mg,

hypromellose – 4.4 mg,

macrogol 6000 – 0.4 mg,

titanium dioxide – 0.2 mg,

carnauba wax – 0.025 mg.

Pregnancy

It is recommended to use Ganaton during pregnancy and lactation only in cases where there is no safer alternative and the expected benefit outweighs the possible risk.

Contraindications

hypersensitivity to itopride or any auxiliary component of the drug;
patients with gastrointestinal bleeding, mechanical obstruction, or perforation;
children’s age (up to 16 years);
pregnancy and lactation period.

Use with caution

Due to the enhancement of acetylcholine by itopride, it should be prescribed with caution due to the possible development of cholinergic adverse reactions in patients for whom their occurrence may aggravate the course of the underlying disease.

Side Effects

From the blood and lymphatic system: leukopenia, thrombocytopenia.

Allergic reactions: skin hyperemia, itching, rash, anaphylaxis.

Endocrine disorders: increased prolactin levels, gynecomastia.

From the nervous system: dizziness, headache, tremor.

From the gastrointestinal tract: diarrhea, constipation, abdominal pain, increased salivation, nausea, jaundice.

Changes in laboratory parameters: increased activity of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transpeptidase, alkaline phosphatase and bilirubin levels.

Interaction

Metabolic interaction is unlikely since itopride is metabolized by flavin monooxygenase and not by CYP450.

With simultaneous use of warfarin, diazepam, diclofenac sodium, ticlopidine hydrochloride, nifedipine and nicardipine hydrochloride, no changes in protein binding were observed.

Itopride increases gastric motility, so it may affect the absorption of other drugs prescribed orally. Particular caution should be exercised when using drugs with a low therapeutic index, as well as sustained-release forms of the active substance or enteric-coated drugs.

Antiulcer agents such as cimetidine, ranitidine, teprenone and cetraxate do not interfere with the prokinetic action of itopride.

Anticholinergics may reduce the effect of itopride.

Overdose

Cases of overdose in humans have not been described. In case of overdose, gastric lavage and symptomatic therapy are indicated.

Storage conditions

List B. At temperatures below 25°C, in a dry place, protected from light. The drug should be stored out of the reach of children.

Shelf life

5 years

Manufacturer

Mailan EPD G.K., Japan