Ganaton (Itoprid)

1 tablet contains:

Active substance:

itoprida hydrochloride - 50 mg;

Excipients:

lactose - 34.975 mg (including excess due to loss in mass 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.

Ganaton - stimulating tone and motility of the gastrointestinal tract.

Pharmacodynamics

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

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

Itoprida hydrochloride activates propulsive motility of the stomach due to antagonism of D2 receptors and dose-dependent inhibition of acetylcholinesterase activity.

Itoprida hydrochloride has a specific effect on the upper gastrointestinal tract, accelerates the transit through the stomach and improves its emptying. Itoprida hydrochloride does not affect serum gastrin levels.

Pharmacokinetics

Suction. Itoprida hydrochloride is rapidly and almost completely absorbed from the digestive tract. Its relative bioavailability is 60%, which is associated with metabolism during the first passage through the liver. Food does not affect bioavailability.

After taking 50 mg of itopride hydrochloride inside, Cmax is reached after 0.5–0.75 hours and amounts to 0.28 μg / ml. When the drug was taken again at a dose of 50-200 mg 3 times / day for 7 days, the pharmacokinetics of the drug and its metabolites was linear, and the cumulation was minimal.

Distribution. It binds to plasma proteins (mainly with albumin) by 96%. The binding to α1-acid glycoprotein is less than 15% of the total binding.

It is actively distributed in tissues (Vd is 6.1 L / kg) and is found in high concentrations in the kidneys, small intestine, liver, adrenal glands and stomach. Penetrates into the brain and spinal cord in minimal quantities. Penetrates into breast milk.

Metabolism. Itopride undergoes active biotransformation in the liver. 3 metabolites have been identified, only one of which exhibits a small activity that does not have pharmacological significance (approximately 2-3% of that of itoprid). The primary metabolite is the N-oxide, which is formed as a result of the oxidation of the Quaternary amino-N-dimethyl group.

Itopride is metabolized by flavin-dependent monooxygenase (FMO3). The amount and effectiveness of FMO3 isoenzymes in humans may vary depending on genetic polymorphism, which in rare cases leads to the development of an autosomal recessive state known as trimethylaminuria (fish smell syndrome). In patients with trimethylaminuria, T1 / 2 of itopride increases.

According to in vivo pharmacokinetic studies, itopride has no inhibitory or inducing effect on CYP2C19 and CYP2E1. Itopride therapy does not affect CYP or uridine diphosphate glucuronizyl transferase activity.

Breeding. Itoprida hydrochloride and its metabolites are excreted mainly in urine. The renal excretion of itopride and its N-oxide after a single oral administration of the drug in therapeutic doses in healthy people was 3.7 and 75.4%, respectively.

The terminal T1 / 2 of itopride hydrochloride is about 6 hours.

Symptomatic treatment of functional non-ulcer dyspepsia (chronic gastritis), in particular relief of:

• Bloating.
• Feelings of quick satiation.
• Pain or discomfort in the upper abdomen.
• Anorexia.
• Heartburn.
• Nausea
• Vomiting

The use of Ganaton during pregnancy and lactation is possible only in cases where there is no safer alternative, and the expected benefit to the mother outweighs the possible risk to the fetus or child.

• hypersensitivity to itoprid or any auxiliary component of the drug;
• gastrointestinal bleeding, mechanical obstruction or perforation of the gastrointestinal tract;
• pregnancy;
• lactation period;
• children under 16 years old.

With caution: the drug should be used in patients for whom the appearance of cholinergic adverse reactions (associated with the increased action of acetylcholine under the influence of itopride) may aggravate the course of the underlying disease.

From the hemopoietic system: leukopenia, thrombocytopenia.

Allergic reactions: flushing of the skin, skin itching, rash, anaphylaxis.

From the endocrine system: increased levels of prolactin, gynecomastia.

From the side of the central nervous system: dizziness, headache, tremor.

From the digestive system: diarrhea, constipation, abdominal pain, increased salivation, nausea, jaundice.

Changes in laboratory parameters: increased activity of AST and ALT, GGT, alkaline phosphatase and bilirubin levels.

Metabolic interaction is hardly possible, because itopride is metabolized under the influence of flavin monooxygenase, and not isoenzymes of the cytochrome P450 system.

With the simultaneous use of Ganaton with warfarin, diazepam, diclofenac sodium, ticlopidine hydrochloride, nifedipine and nicardipine hydrochloride, no changes in the binding of itopride to proteins were observed.

Itopride enhances gastric motility, so it can affect the absorption of other drugs used simultaneously inside. Particular care should be taken when using drugs with a low therapeutic index, as well as forms with a slow release of the active substance or preparations with enteric coating.

Antiulcer drugs, such as cimetidine, ranitidine, teprenone and cetraxate, do not affect the prokinetic effect of itopride.

Anticholinergics can weaken the effect of itopride.

Adults: appoint inside 50 mg (1 tablet) 3 times a day before meals.

The recommended daily dose is 150 mg.

The indicated dose can be reduced taking into account the age of the patient.

Cases of overdose in humans are not described.

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

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

Tablets