Ganaton tablets p / o 50mg, No. 40

• 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.

Inside, adults - 50 mg (1 tab.) 3 times a day before meals.

The recommended daily dose is 150 mg.

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

Film-coated tablets

active substance: itopride hydrochloride

• Hypersensitivity to itopride or any auxiliary component of the drug;

• gastrointestinal bleeding, mechanical obstruction or perforation of the gastrointestinal tract;

• pregnancy;

• lactation period;

• children under 16 years of age.

The drug should be used with caution in patients for whom the appearance of cholinergic side reactions (associated with an increase in the action of acetylcholine under the influence of itopride) may aggravate the course of the underlying disease.

pharmachologic effect

Pharmacodynamics Itoprid hydrochloride is a gastroprokinetic drug for oral administration. The dosage form and composition of the tablets provide an immediate release of the active substance. Itopride is characterized by a dual mechanism of action: antagonism to D2-dopamine receptors and inhibition of acetylcholinesterase. As a result of the action of itopride, the concentration of acetylcholine increases, which leads to increased gastric motility, increased tone of the lower esophageal sphincter (LES), accelerated gastric emptying and improved gastroduodenal coordination. Itopride hydrochloride also has an antiemetic effect by interacting with D2-dopamine receptors located in the chemoreceptor trigger zone of the medulla oblongata. Itopride causes dose-dependent suppression of apomorphine-induced vomiting.The effect of the drug in patients with functional dyspepsia leads to a decrease in the severity of symptoms (overall patient assessment, postprandial heaviness in the abdomen, early satiety). The use of itopride in patients with diabetic gastroparesis facilitated the acceleration of liquid and solid food evacuation from the stomach. In patients with gastroesophageal reflux disease (GERD), itopride reduces the amount of transient relaxation of the lower esophageal sphincter and reduces the length of time with high acidity in the esophagus (pH <4). With the combined use of itopride hydrochloride with alpha-lipoic acid, an acceleration of the gastric emptying process and a decrease in the level of gastrin and motilin were observed in comparison with itopride monotherapy. Itopride hydrochloride has a highly specific effect on the upper gastrointestinal tract.Itopride hydrochloride accelerates gastric emptying. Itopride hydrochloride does not affect serum gastrin levels.

Pharmacokinetics

Suction

Itopride hydrochloride is rapidly and almost completely absorbed from the gastrointestinal tract. The relative bioavailability is 60%, which is related to the metabolism at the 'first pass' through the liver. Food has no effect on bioavailability. Cmax in blood plasma (0.28 ?g / ml) is achieved within 0.5-0.75 hours after taking 50 mg of itoprid hydrochloride. With repeated administration of itopride hydrochloride orally 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

Itopride hydrochloride binds 96% to plasma proteins, mainly albumin. Binding to alpha1-acid glycoprotein is less than 15% of the total binding. Itopride is actively distributed in tissues (Vd? = 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 Itoprid undergoes active biotransformation in the human liver. Three metabolites have been identified, only one of which exhibits little activity, which has no pharmacological significance (approximately 2-3% of that of itopride). The primary metabolite in humans is the N-oxide, which is formed by oxidation of the tertiary amino-N-dimethyl group.Itopride is metabolized by flavin-dependent monooxygenase (FMO3). The amount and potency of FMO isoenzymes in humans can differ depending on genetic polymorphism, which rarely leads to the development of an autosomal recessive condition known as trimethylaminuria (fishy odor syndrome). According to pharmacokinetic studies of CYP-mediated reactions in vivo, itopride has no inhibitory or inducing effect on the isoenzymes CYP2C19 and CYP2E1. Itopride therapy does not affect CYP or uridine diphosphate glucuronyltransferase activity.known as trimethylaminuria (fishy odor syndrome). According to pharmacokinetic studies of CYP-mediated reactions in vivo, itopride has no inhibitory or inducing effect on the isoenzymes CYP2C19 and CYP2E1. Itopride therapy does not affect CYP or uridine diphosphate glucuronyltransferase activity.known as trimethylaminuria (fishy odor syndrome). According to pharmacokinetic studies of CYP-mediated reactions in vivo, itopride has no inhibitory or inducing effect on the isoenzymes CYP2C19 and CYP2E1. Itopride therapy does not affect CYP or uridine diphosphate glucuronyltransferase activity.

Withdrawal

Itopride hydrochloride and its metabolites are excreted mainly in the urine. The renal excretion of itopride and its N-oxide after a single oral administration of the drug in a therapeutic dose (50 mg) in healthy people was 3.7 and 75.4%, respectively. T1 / 2 of itopride hydrochloride is about 6 hours.

Side effect

From the gastrointestinal tract: often - abdominal pain, diarrhea; infrequently - increased salivation.

Laboratory and instrumental data: infrequently - an increase in ALT activity, a decrease in the number of leukocytes.

From the nervous system: infrequently - dizziness, headache.

Skin and subcutaneous tissue disorders: infrequently - rash.

The following side effects were identified during post-registration use, based on the available data, it is not possible to estimate their frequency.

On the part of the blood and lymphatic system: leukopenia and thrombocytopenia.

From the immune system: hypersensitivity reactions, including anaphylactoid reaction.

From the endocrine system: an increase in the level of prolactin in the blood.

From the nervous system: dizziness, headache, tremors.

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

From the liver and biliary tract: jaundice.

On the part of the skin and subcutaneous tissues: rash, erythema and itching.

On the part of the genitals and mammary gland: gynecomastia.

Laboratory and instrumental data: increased activity of ACT, ALT, GGT, alkaline phosphatase and the level of bilirubin.

Application during pregnancy and lactation

Pregnancy At the moment, there is a limited amount of data (less than 300 pregnancy outcomes) on the use of itopride in pregnant women. Animal studies have not revealed signs of direct or indirect adverse effects of itopride, indicating reproductive toxicity. As a precaution, you should avoid using itopride during pregnancy.

Breastfeeding period

Itopride is excreted in milk in animals, but at the moment there is not enough data on the excretion of itopride in human breast milk. When breastfeeding, the risk of the drug's influence on the baby cannot be excluded. The decision to stop breastfeeding or to withdraw / interrupt the drug should be made based on an assessment of the benefits of breastfeeding for the baby and the benefits of the drug for the mother.

Fertility

There are no data on the effect of itopride on fertility in humans. However, animal studies have shown no signs of a negative effect of the drug on fertility.

Application in children

Contraindication: children under 16 years of age. Use in elderly patients Itoprid should be prescribed with caution to elderly patients due to frequent decrease in liver and kidney function, the presence of concomitant diseases or other treatment.

special instructions

Itopride enhances the action of acetylcholine and can cause cholinergic side reactions. There are no data on long-term use of the drug. Influence on the ability to drive vehicles and mechanisms No studies have been conducted on the effect of itopride on the ability to drive vehicles and mechanisms. However, during the period of drug treatment, care should be taken when performing potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions (driving vehicles, working with moving mechanisms, the work of a dispatcher and an operator), because use of the drug may cause dizziness.

Overdose

Treatment: in case of an overdose, gastric lavage and symptomatic therapy are indicated.

Drug interactions

Metabolic interactions are not expected as itopride is primarily metabolized by flavin monooxygenase, and not by the cytochrome CYP450 system. With the 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 can interfere with the absorption of other drugs taken by mouth. Particular care should be taken when using drugs with a low therapeutic index, as well as sustained-release or enteric-coated drugs. Antiulcer drugs such as cimetidine, ranitidine, teprenone, and cetraxate do not interfere with the prokinetic effect of itopride. Anticholinergics can weaken the effect of itopride.