Neobutin^® Retard (Tablets) Instructions for Use

Marketing Authorization Holder

Aliym, JSC (Russia)

Contact Information

BINNOPHARM GROUP LLC (Russia)

ATC Code

A03AA05 (Trimebutine)

Active Substance

Trimebutine (Rec.INN registered by WHO)

Dosage Form

Neobutin® Retard

Extended-release film-coated tablets, 300 mg: 5, 10, 15, 20, 30, 40, or 60 pcs.

Dosage Form, Packaging, and Composition

Extended-release film-coated tablets white or almost white, oblong in shape with rounded ends, biconvex; the core on the cross-section is white or almost white.

Excipients: lactose monohydrate – 180 mg, tartaric acid, hypromellose (hydroxypropyl methylcellulose), povidone K30, colloidal silicon dioxide (aerosil), magnesium stearate.

Excipients for the coating: hypromellose (hydroxypropyl methylcellulose), talc, ready-made mixture for white film coating [titanium dioxide, denatured ethanol (methylated spirit), hypromellose-2910, water], silicone defoamer.

5 pcs. – blister packs (1, 2, 3, 4, 6) – cardboard packs.
10 pcs. – blister packs (1, 2, 3, 4, 6) – cardboard packs.

Clinical-Pharmacological Group

Spasmolytic drug

Pharmacotherapeutic Group

Spasmolytic agent

Pharmacological Action

Trimebutine, acting on the enkephalinergic system of the intestine, is a regulator of its peristalsis.

Acting on peripheral δ-, μ- and κ-receptors, including those located directly in the smooth muscles throughout the gastrointestinal tract, it regulates motility without affecting the central nervous system.

Thus, Trimebutine restores the normal physiological activity of the intestinal muscles in various gastrointestinal diseases associated with motility disorders.

By normalizing visceral sensitivity, Trimebutine provides an analgesic effect in abdominal pain syndrome.

Pharmacokinetics

Absorption

After oral administration, Trimebutine is rapidly absorbed from the gastrointestinal tract.

Distribution

V_d – 88 L. Binding to plasma proteins is low – about 5%. Trimebutine slightly penetrates the placental barrier.

Metabolism

Trimebutine is biotransformed in the liver. In a study in healthy volunteers after a single dose of 300 mg of trimebutine, the pharmacokinetic parameters of the active metabolite of trimebutine – 2-methylamino-2-phenylbutyl-3,4,5-trimethoxybenzoate (desmethyltrimebutine) were: C_max – 441.45 ± 252.99 ng/ml; T_max – 2.20 ± 1.01 hours; mean residence time (MRT) – 17.12 ± 3.14 hours; T_1/2 – 12.52 ± 4.54 h; V_d – 1279.72 ± 1108.53 L; total clearance – 66.51 ± 34.34 L/h.

Excretion

Trimebutine is excreted in the urine mainly as metabolites (approximately 70% within the first 24 hours).

Preclinical safety data

Preclinical data obtained from standard studies of pharmacological safety, repeated dose toxicity, genotoxicity, carcinogenic potential, and reproductive and ontogenetic toxicity did not reveal any particular risk to humans.

Indications

• Symptomatic treatment of pain, spasms and discomfort in the abdomen, feeling of bloating (flatulence), intestinal motility disorders with changes in stool frequency (diarrhea or constipation), dyspepsia, heartburn, belching, nausea, vomiting associated with functional diseases of the gastrointestinal tract and biliary tract:
  • Non-erosive form of gastroesophageal reflux disease;
  • Cholelithiasis;
  • Biliary tract dysfunction;
  • Irritable bowel syndrome;
  • Sphincter of Oddi dysfunction;
  • Postcholecystectomy syndrome.
• Postoperative paralytic ileus.

ICD codes

Dosage Regimen

Orally, at least 60 minutes before meals, without chewing, with water.

Adults and children over 12 years old 300 mg 2 times/day (with a 12-hour interval).

The course of treatment for abdominal pain associated with functional diseases of the digestive tract and biliary tract, including irritable bowel syndrome, is 28 days.

To prevent relapse of irritable bowel syndrome after the completed course of treatment (4 weeks) during the remission period, it is recommended to continue taking the drug at a dose of 300 mg/day for 12 weeks.

Adverse Reactions

The adverse effects listed below are presented according to the following frequency gradations: very common (≥1/10), common (≥1/100 but <1/10), uncommon (≥1/1000 but <1/100), rare (≥1/10000 but <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

From the digestive system frequency unknown – dry mouth, unpleasant taste sensations, diarrhea, dyspepsia, nausea, constipation.

From the immune system frequency unknown – skin rash.

From the nervous system frequency unknown – drowsiness, fatigue, dizziness, headache, anxiety.

From the kidneys and urinary tract frequency unknown – menstrual cycle disorders, urinary retention.

From the endocrine system painful breast enlargement.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration to ensure continuous monitoring of the benefit-risk ratio of the drug. Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to trimebutine maleate and/or to any of the excipients included in the drug;
• Children under 12 years of age (for this dosage form);
• Pregnancy;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

Use in Pregnancy and Lactation

Pregnancy

Experimental studies have not revealed data on the teratogenicity and embryotoxicity of trimebutine. Nevertheless, due to the lack of necessary clinical data, the use of trimebutine during pregnancy is contraindicated.

Lactation period

It is not recommended to prescribe Trimebutine during lactation due to the lack of reliable clinical data confirming the safety of trimebutine use during this period. If it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Pediatric Use

The use of the drug in children under 12 years of age is contraindicated.

Special Precautions

A course of treatment for irritable bowel syndrome in the acute period at a dose of 600 mg/day for 4 weeks and continuation of treatment after the completed course at a dose of 300 mg/day for 12 weeks helps to avoid relapse of the disease.

Excipients

The drug Neobutin^® Retard contains lactose monohydrate. Patients with rare lactose intolerance, lactase deficiency, glucose-galactose malabsorption should not take this drug.

Effect on the ability to drive vehicles and mechanisms

The drug does not have a sedative effect, does not affect the speed of psychomotor reactions and can be used by individuals of various professions, including those requiring increased attention and coordination of movements. However, given the possible side effects that may affect these abilities (dizziness and others), caution should be exercised when driving vehicles and engaging in other potentially hazardous activities.

Overdose

Symptoms no cases of trimebutine overdose have been reported to date.

Treatment drug withdrawal, gastric lavage, administration of activated charcoal, symptomatic therapy. Specific antidotes are absent.

Drug Interactions

Interaction studies of the drug Neobutin^® Retard have not been conducted.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years. Do not use after the expiration date.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.