PRIMER

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PRIMER (PRIMER)

Composition:

Active substance: 1 coated tablet contains 50 mg of itopride hydrochloride;

Excipients: corn starch, lactose monohydrate, sodium croscarmellose, povidone, magnesium stearate, colloidal anhydrous silicon dioxide, sodium starch glycolate (type A), hypromellose, talc, titanium dioxide (E 171), propylene glycol.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: almost white with small specks, round, coated tablets.

Pharmacotherapeutic group. Agents used in functional gastrointestinal disorders. Peristalsis stimulants. ATC code A03FA.

Pharmacological Properties

Pharmacodynamics

Itopride hydrochloride is a dopamine D2 receptor antagonist with anti-cholinesterase activity. Itopride hydrochloride enhances acetylcholine release and inhibits its degradation.

Based on its antagonism of dopamine D2 receptors, itopride hydrochloride exerts a tonic effect on gastrointestinal smooth muscle. By inhibiting acetylcholinesterase activity, it stimulates gastric motility, increases the duration of antral and duodenal contractions, accelerates gastric emptying, improves gastroduodenal coordination, and enhances intestinal transit.

Itopride hydrochloride also exerts antiemetic effects through interaction with D2 receptors located in the chemoreceptor trigger zone, as demonstrated by dose-dependent inhibition of apomorphine-induced vomiting in animals.

The action of itopride hydrochloride is highly specific to the upper gastrointestinal tract.

Itopride hydrochloride does not affect serum gastrin levels.

Pharmacokinetics

Approximately 90% of itopride hydrochloride is absorbed in the intestine. Maximum plasma concentration is reached within 45 minutes after oral administration of the tablet. Food intake does not affect the absorption of itopride hydrochloride. Itopride hydrochloride does not cross the blood-brain barrier or penetrate into the cardiac conduction system.

It undergoes hepatic acetylation and oxidation via flavin-containing monooxygenase, forming inactive metabolites that are excreted by the kidneys. The elimination half-life of itopride hydrochloride is 6 hours. It is completely eliminated within 12 hours after a single dose and does not accumulate.

Clinical characteristics.

Indications.

Treatment of gastrointestinal symptoms of functional non-ulcer dyspepsia and chronic gastritis, namely:

• abdominal bloating;
• early satiety;
• pain and discomfort in the upper abdomen;
• anorexia;
• heartburn;
• nausea;
• vomiting.

Contraindications.

• Hypersensitivity to the active substance or to any component of the medicinal product.
• Conditions in which increased gastrointestinal motility may be harmful, e.g., gastrointestinal bleeding, mechanical obstruction, or perforation.
• Elevated serum prolactin levels.
• Pregnancy, except when the expected benefit outweighs the potential risk.
• Breastfeeding.

Interaction with other medicinal products and other forms of interaction.

Metabolic interactions are not expected because itopride hydrochloride is primarily metabolized by flavin-containing monooxygenase, not by cytochrome P450 isoenzymes.

No changes in protein binding were observed when itopride hydrochloride was co-administered with warfarin, diazepam, sodium diclofenac, ticlopidine hydrochloride, nifedipine, or nicardipine hydrochloride. Since itopride hydrochloride enhances gastric motility, it may affect the absorption of other medicinal products when administered concomitantly. Particular caution is required when using medicinal products with a narrow therapeutic index, sustained-release formulations, or enteric-coated preparations.

Anti-ulcer agents such as cimetidine, ranitidine, teprenone, and cetraxate do not affect the prokinetic action of itopride hydrochloride.

Anticholinergic medicinal products may reduce the therapeutic effect of itopride hydrochloride.

Special precautions for use

Hydrochloride of itopride enhances the effect of acetylcholine and may cause cholinergic adverse reactions. Safety data on long-term use (more than 8 weeks) are lacking.

Elderly patients, due to their reduced liver and kidney function, concomitant diseases, or concurrent therapy with other medicinal products, should be treated with caution when using itopride because of the possible increased risk of adverse reactions.

If a dose is missed, it should be taken as soon as possible; however, if it is almost time for the next dose, the missed dose should be skipped and the next dose taken at the regular time; doses should not be doubled.

If galactorrhea or gynecomastia occur, for example, temporary discontinuation or complete withdrawal of the drug is necessary.

In case of leukopenia or neutropenia being detected, treatment with the drug should be discontinued.

The product contains lactose; therefore, patients with established sugar intolerance should consult their physician before taking this medicinal product.

Use during pregnancy or breastfeeding

Pregnancy

The safety of hydrochloride of itopride during pregnancy has not been established. Therefore, the drug should not be used during this period unless the expected benefit outweighs the potential risk.

Breastfeeding period

Hydrochloride of itopride passes into breast milk, as demonstrated in animal studies. In order to prevent possible adverse reactions in infants, an appropriate decision should be made whether to discontinue breastfeeding or to stop the treatment, taking into account the importance of the therapy for the mother.

Ability to affect reaction speed when driving vehicles or operating machinery

There is no information available regarding a possible effect on reaction speed. However, when deciding whether to drive vehicles or operate machinery, the possibility of dizziness occurring should be taken into account.

Dosage and Administration.

Adults are prescribed 1 tablet (50 mg) 3 times daily, taken orally before meals, without chewing, and swallowed with sufficient amount of water.

The recommended daily dose is 150 mg. This dose may be reduced depending on clinical symptoms and patient's age (see "Special Warnings").

In patients with impaired liver or kidney function, the drug should be administered under strict medical supervision; if necessary, the dose should be reduced or therapy discontinued.

Treatment duration should be determined by a physician. In clinical trials, the duration of treatment with itopride hydrochloride was up to 8 weeks.

Children

There is no experience with use in children.

Overdose.

No cases of overdose have been reported.

Treatment. In case of excessive overdose, gastric lavage should be performed and symptomatic treatment administered.

Adverse reactions.

Immune system: hypersensitivity reactions, anaphylactoid reaction.

Skin and subcutaneous tissue: allergic reactions, including rash, pruritus, erythema.

Blood and lymphatic system: leukopenia, neutropenia, thrombocytopenia (see section "Special precautions for use").

Gastrointestinal tract: dry mouth, diarrhea, constipation, abdominal pain, increased salivation, nausea.

Hepatobiliary system: jaundice.

Endocrine system: possible increase in blood prolactin levels, gynecomastia, galactorrhea (see section "Special precautions for use").

Nervous system: dizziness, headache, sleep disturbances, insomnia, tremor.

Renal and urinary system: increased blood urea and creatinine levels, increased creatinine in urine, urinary retention in patients with prostatic hyperplasia.

Other: increased fatigue, increased irritability, back pain.

Laboratory findings: increased levels of AST, ALT, GGT, alkaline phosphatase, and bilirubin.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C, in the original packaging, in a place inaccessible to children.

Packaging.

10 tablets per blister, 1 blister per cardboard box.

Prescription status. Prescription only.

Manufacturer.

Mepro Pharmaceuticals Private Limited.

Manufacturer's address.

Unit II, Q-Road, Phase IV, GIDC, Vadodhan, Surendranagar, Gujarat, 363 035, India.

Marketing Authorization Holder. Mili Healthcare Limited.

Address of the Marketing Authorization Holder. 2nd Floor, Office Premises, 4 Charterfield House, Castle Street, Taunton, Somerset, England, TA1 4AS, United Kingdom.