Indications:
Treatment of gastrointestinal symptoms caused by chronic gastritis (bloated feeling, upper abdominal pain or discomfort, anorexia, heartburn, nausea and vomiting).
Dosage and administration:
Administration: ITOPAGI tablets are orally administered before meals.
Dosage:
The usual oral dosage for adults is 50 mg, 3 times a day.
The dose may be reduced according to the patient’s age and symptoms.
Some special attention on the handling of the medicine before and after use:
There are no special requirements for handling this medicine after use.
Contraindications:
Hypersensitivity to itopride or any of the excipients of the drug.
Pregnant women or nursing women (unless absolutely necessary).
Itopride use is contraindicated in children.
Warnings and precautions for use:
Conditions where caution should be taken:
This drug should be used with caution since it enhances the action of acetylcholine. This drug should not be consumed continuously for an extended period when no improvement of gastrointestinal symptoms is observed.
Use in the elderly:
Since the elderly often have a physiological hypofunction, they are prone to adverse reactions and should thus be closely monitored. If adverse reactions are evident, appropriate measures such as reduction or cessation of the drug should be implemented.
Pediatric use:
The safety of this product in children has not been established (There is limited clinical experience).
Pregnancy and lactation:
Pregnancy:
This drug should be given to pregnant women or women who may become pregnant only when it is considered that the expected therapeutic benefits outweigh the risks (Safety during pregnancy has not been established.)
Lactation:
Ideally, this drug should not be given to women during lactation, but if its administration is required, breast feeding should be avoided. It has been reportedly excreted in breast milk in animal studies (rats). (See section Pharmacokinetics)
Effects on ability to drive and use machines:
Itopride may cause dizziness. The ability to drive and operate machines may be impaired; therefore, caution should be exercised when driving or operating machinery if ITOPAGI tablet is being taken.
Interactions, incompatibilities of medicine:
Interaction with other medicinal products and other forms of interaction:
Itopride should be administered with care when coadministered with the following drugs:
| Drug names | Signs, symptoms and
treatment procedures |
Mechanism and
risk factors |
| Anticholinergic drugs: Tiquizium bromide, scopolamine butyl
bromide, timepidium bromide, etc. |
Symptoms:
There is a possibility of reducing the action of this product that activates gastrointestinal motility (cholinergic action). |
Mechanism: Inhibitory action of
anticholinergic drugs pharmacologically opposes the action of itopride. |
Incompatibilities:
Because there are no studies about the incompatibility of the medicine, it should not be mixed with other medicines.
Undesirable effects:
Clinically significant adverse reactions:
Shock and anaphylactoid reactions (frequency unknown): Shock and anaphylactoid reactions may occur, and close observation should be made. If any signs of hypotension, dyspnoea, larynx edema, urticaria, pallor and diaphoresis etc. occur, the drug should be discontinued and appropriate measures are implemented.
Hepatic function disorder and jaundice (incidence unknown): Hepatic function disorder and jaundice with increased AST (GOT), ALT (GPT) and γ-GTP etc., may occur, and close observation should be made. If abnormalities occur, the drug should be discontinued and appropriate therapeutic measures are implemented.
Other adverse reactions:
5% >ADR ≥ 0.1%
Gastrointestinal: Diarrhea, constipation, abdominal pain.
Hepatic: Increased AST (GOT), increased ALT (GPT).
ADR < 0.1%
Extrapyramidal symptoms: Tremor.
Endocrine: Increased prolactin.
Hematologic: Thrombocytopenia, leucopenia.
Gastrointestinal: Nausea, increased saliva.
Psychoneurologic: Headache, irritated feeling, sleep disorder, dizziness.
Hepatic: Increased γ-GTP.
Renal: Increased BUN, increased creatinine.
Others: Thoracodorsal pain, fatigue.
Incidence is unknown:
Hypersensitivity: Rash, redness, itching.
Endocrine: Gynecomastia.
If any above abnormal symptoms occur, appropriate measures and drug discontinuation should be considered.
Overdosage and management:
Overdose:
There are no data on the use of drug overdose. The recommended doses should not be exceeded.
Management:
In case of an overdose, common measures such as gastric lavage and symptomatic treatment should be applied. Actively monitor for timely remedies.
Pharmacodynamics:
Pharmacotherapeutic group: Propulsives.
ATC code: A03FA07.
Mechanism of action:
Itopride hydrochloride increases gastrointestinal motility with dual mechanism. It enhances the release of acetylcholine (ACh) through dopamine D2-receptor antagonistic action and inhibits the decomposition of released ACh through its acetylcholine esterase (AChE) inhibitory action.
Activator action of the gastrointestinal motility:
Activation of the gastric motility: The gastric motility in non-anesthetized dogs is activated in a dose-dependent manner.
Activation of the gastric emptying ability: The gastric emptying ability in humans, dogs and rats is activated.
Alleviation of vomiting:
Apomorphine-induced vomiting is inhibited in dogs in a dose-dependent manner.
Pharmacokinetics:
Serum concentrations:
The serum concentrations and pharmacokinetic parameters in healthy adults, after a single oral administration of 50 mg of itopride hydrochloride in the fasting state, are shown in the following Figure 1 and Table 1.
Figure 1: Serum concentrations after a single oral administration of 50 mg of itopride hydrochloride (Healthy adults in the fasting state, mean value ± S.E.)
Table 1: Pharmacokinetic parameters
Mean value ± standard deviation, n = 6
Distribution:
Results of the animal study:
The concentrations peaked in almost all tissues at 1 to 2 hours after a single oral administration of 5 mg/ kg of 14C-itopride hydrochloride to rats, while the level at 2 hours after administration was high in the kidneys, small intestines, liver, adrenal glands, and stomach in order of magnitude (high to low) and the transfer into the central nervous system, such as brain and spinal marrow, was minimal.
In intraduodenal administration of 5 mg/kg of 14C-itopride hydrochloride to rats, the radioactivity concentrations in the gastric muscular layers were about twice as high as those in the blood.
Excretion in breast milk: When 5 mg/kg of 14C-itopride hydrochloride was orally administered to rats, concentrations of radioactivity in breast milk in comparison to serum concentrations of radioactivity were 1.2 times higher in Cmax, 2.6 times higher in AUC, and 2.1 times higher in T1/2.
Metabolism and excretion:
At a single oral administration of 100 mg of this drug to healthy adults (6 men) in the fasting state, the urinary excretion rate within 24 hours after administration peaked in the N-oxide form [67.54% of the dose (89.41% of the urinary excretion)], followed by unchanged compound (4.14%) and the level in other metabolites were minimal.
In the experiments using microsomes that express a human CYP or flavine containing monooxygenase (FMO), it showed that FMO1 and FMO3 were involved in the production of the main metabolic N-oxide form. However, no involvement of N-oxygenase activity of CYP1A2, -2A6, -2B6, -2C8, -2C9, 2C19, 2D6, 2E1, or 3A4 was detected.
Others:
Serum protein binding ratio: Serum protein binding ratio was 96% after a single oral administration of 100 mg of itopride hydrochloride to healthy adults (6 men) in the fasting state.
Storage conditions, shelf-life, quality specification of the medicine:
Storage conditions: Protect from humidity and light, below 300C.
Shelf-life: 36 months from the manufacture date.
Quality specification: In house.
