Kolofort^® (Tablets) Instructions for Use

Marketing Authorization Holder

Materia Medica Holding NPF, LLC (Russia)

Contact Information

MATERIA MEDICA HOLDING NPF LLC (Russia)

ATC Code

A03C (Spasmolytics in combination with psycholeptics)

Dosage Form

Kolofort®

Sublingual tablets: 100 pcs.

Dosage Form, Packaging, and Composition

Sublingual tablets from white to almost white in color, flat-cylindrical in shape, with a score and a bevel; on the flat side with a score, the inscription MATERIA MEDICA is applied, on the other flat side the inscription KOLOFORT is applied.

* EMD – units of modifying action.

Excipients: lactose monohydrate, microcrystalline cellulose, magnesium stearate.

20 pcs. – blister packs (5) – cardboard packs.

Clinical-Pharmacological Group

Spasmolytic drug with anti-inflammatory and anxiolytic action

Pharmacotherapeutic Group

Means for the treatment of functional disorders of the gastrointestinal tract; spasmolytics in combination with psycholeptics

Pharmacological Action

Experimental studies have shown that the active components of the drug modify the ligand-receptor interaction of endogenous regulators with serotonin receptors, sigma₁ receptors, TNF-α receptors, and H₄-histamine receptors localized in the gastrointestinal tract (GIT).

The combination of three active components allows for a complex effect on the central and peripheral links of the pathogenesis of functional bowel disorders, including abdominal pain syndrome.

Antibodies to protein S-100 have a wide range of psychotropic activity, including anxiolytic, antidepressant, antiasthenic, and nootropic effects, which is clinically manifested in the elimination of internal tension, anxiety, normalization of a number of visceral functions, including the activity of the large intestine. They do not have a sedative effect, cause no addiction, or withdrawal syndrome.

Antibodies to TNF-α have a pronounced anti-inflammatory effect and contribute to the normalization of the balance of pro-inflammatory and anti-inflammatory cytokines.

Antibodies to histamine have a spasmolytic, anti-inflammatory, and anti-edema effect.

The combined use of components in the combined preparation contributes to the normalization of nervous and humoral regulation of intestinal function; reduction of visceral hypersensitivity of colon receptors to stretching, ensuring the restoration of impaired gastrointestinal motility; relief of the feeling of abdominal bloating and stomach fullness, reduction of the severity of pain syndrome. The spasmolytic effect of the drug is manifested by relaxation of smooth muscles and a decrease in the tone of the gastrointestinal tract wall, a decrease in intraluminal pressure, normalization of stool consistency, its frequency and accompanying symptoms (relief of imperative urges, tenesmus, feeling of incomplete bowel emptying, additional efforts during defecation, etc.).

Clinical efficacy and safety

It has been clinically established that the drug Kolofort^® is an effective and safe drug for the treatment of irritable bowel syndrome (IBS) and functional dyspepsia (FD).

In a multicenter, double-blind, placebo-controlled clinical study of the treatment of various types of IBS (IBS with diarrhea/constipation predominance and mixed type), the drug Kolofort^® had a pronounced analgesic effect, which was manifested by a significant reduction in the severity of the main symptom of the disease – abdominal pain – in patients with all types of IBS. Abdominal pain, which was assessed on an 11-point visual analog scale (VAS) from the initial severe/moderate intensity, decreased by 30% or more after 12 weeks of treatment in 90% of participants (compared to 67% in the placebo group; p=0.003). In 31% of study participants, abdominal pain was completely relieved by the end of the treatment period (intensity reduction by 90-100%); in the placebo group, there were half as many such patients (16%). Thus, treatment with the drug Kolofort^® eliminated motor and receptive visceral dysfunction of the intestine and hyperalgesia by influencing the central and peripheral mechanisms of abdominal pain formation, significantly reduced its severity and reduced the need for analgesic (antispasmodic/spasmolytic) therapy. The pronounced analgesic effect developed gradually and was noted in 100% of patients.

The therapeutic effect of the drug Kolofort^® was manifested by a positive effect on the stool pattern (shape and frequency) in patients with various types of IBS. In patients with “IBS with diarrhea predominance”, improvement in stool consistency/form according to the Bristol Stool Scale began from the 2nd week of using the drug Kolofort^®. By the end of the three-month course of therapy, 96% of patients in the Kolofort^® group had the 5th, 4th, 3rd (normal) type of stool (p=0.02); while its frequency decreased from 3 times or more to 1-2 times per day. The effect of the drug Kolofort^® in patients with “IBS with constipation predominance” manifested in the first two weeks of treatment and progressively increased during therapy. The average stool frequency increased from the initial 1-2 times a week to 5.4±2.1 times per 7 days. The use of the drug Kolofort^® significantly reduced the manifestation of intestinal symptoms (discomfort, flatulence, bloating, nausea, vomiting, diarrhea, constipation), and a decrease in the percentage of patients with imperative urges for defecation and a feeling of incomplete bowel emptying was also noted during treatment. Treatment with the drug Kolofort^® led to an increase in physical and mental performance, a decrease in irritability and emotional lability, and an improvement in the quality of life.

There was a decrease in the proportion of patients with subclinically/clinically significant anxiety/depression, and an increase in the percentage of patients without signs of anxiety disorders and depression. The use of the drug Kolofort^® made it possible to reduce the need for the use of symptomatic drugs to relieve abdominal pain and normalize stool.

The drug Kolofort^® is well tolerated and compatible with other drugs used to treat concomitant pathological conditions. The drug Kolofort^® is effective and safe in the treatment of IBS; during the clinical study of the drug, the frequency of adverse events (AEs) in the Kolofort^® group did not exceed that in the placebo group.

All AEs had no definite connection with the drug intake.

In a multicenter, double-blind, placebo-controlled, randomized clinical study of the treatment of patients with functional dyspepsia, the therapeutic effect of the drug Kolofort^® was manifested in a significant reduction in the severity of dyspepsia symptoms (nausea, vomiting, bloating, spasmodic abdominal pain, feeling of early satiety, heartburn/sour belching, feeling of weakness combined with pain and nausea, lack of appetite, chest pain, epigastric pain), which were assessed on the Gastrointestinal Symptom Scale (GIS). By the end of the treatment period (8 weeks), the reduction in the average total score on the GIS scale in the Kolofort^® group significantly exceeded the results obtained in the placebo group and amounted to 7.2±3.3 points and 6.3±4.6 points, respectively (p=0.041). An additional analysis of efficacy by patient categories (reduction by 1, 2, 3, 4 or more points) showed that against the background of taking the drug Kolofort^® for 8 weeks, the severity of gastrointestinal symptoms on the GIS scale decreased by 2 points from the initial values in 96.4% of patients (p=0.055) and by 4 points in 88.6% of study participants (p=0.051).

In the Kolofort^® group, no patients were identified in whom FD symptoms persisted or progressed, leading to the prescription of concomitant therapy drugs (proton pump inhibitors, prokinetics, antispasmodics).

The therapy, along with a significant reduction in the severity of gastrointestinal symptoms, may contribute to a decrease in the influence of dyspepsia symptoms on the patient’s quality of life. Analysis of data from the SF-36 questionnaire revealed a tendency to improve the quality of life of patients with functional dyspepsia on the “mental health” subscale. After 8 weeks of therapy, the change in the average total score was 3.5±6.3 in the Kolofort^® group and 2.9±6.6 in the placebo group (p=0.375).

During the study, no clinically significant changes in vital signs, such as blood pressure, heart rate, and respiratory rate, were detected. Not a single serious case of an adverse event (AE) was registered, nor were there any AEs with a definite/probable connection to the study therapy. The frequency distribution of AEs depending on the severity and reliability of the causal relationship with the study therapy did not differ between the Kolofort^® and placebo groups.

Preclinical safety data

Preclinical safety studies, including studies of acute and chronic toxicity, genotoxicity, reproductive toxicity, immunotoxicity, sensitizing and local irritant properties, did not reveal the presence of negative and potentially dangerous effects of the drug Kolofort^® for humans.

Pharmacokinetics

Pharmacokinetic studies are impossible due to the complex composition of the drug.

Indications

The drug Kolofort^® is indicated for use in adults

• Irritable bowel syndrome, including stress-related, manifested by symptoms such as abdominal pain, constipation, diarrhea, flatulence, bloating, nausea and vomiting;
• Functional dyspepsia, manifested by nausea, vomiting, abdominal bloating, spasmodic abdominal pain, feeling of early satiety, heartburn/sour belching.

ICD codes

Dosage Regimen

The score is not intended for breaking the tablet.

The recommended dose for adults is 2 tablets per dose. The tablets should be held in the mouth, without swallowing, until completely dissolved. The drug should be taken not during meals.

Irritable bowel syndrome

Take 2 tablets 2 times a day. The course of treatment is at least 1 month; the recommended course of treatment is 3 months; if necessary, the course of treatment can be extended up to 6 months and/or repeated after 1-2 months.

Functional dyspepsia

Take 2 tablets 2 times a day. The recommended course of treatment is 2 months.

Children

The safety and efficacy of the drug Kolofort^® in children aged 0 to 18 years have not been established to date. Since clinical studies have not been conducted in this age group, data are not available.

Adverse Reactions

Possible reactions of increased individual sensitivity to the components of the drug.

Contraindications

• Hypersensitivity to the active substances or to any of the excipients included in the drug.

Use in Pregnancy and Lactation

Pregnancy

The drug should not be taken during pregnancy. Data on the use of the active substances of the drug Kolofort^® in pregnant women are not available.

Lactation period

The drug should not be taken during lactation. Information on the penetration of the active substances (metabolites) of the drug Kolofort^® into human breast milk is not available.

Pediatric Use

The use of the drug is contraindicated under the age of 18 years.

Special Precautions

Excipients

The drug contains lactose, therefore patients with rare hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take this drug.

Effect on the ability to drive vehicles and mechanisms

The drug does not affect the ability to drive vehicles and other potentially dangerous mechanisms.

Overdose

Symptoms of overdose may include dyspeptic phenomena due to the excipients included in the drug.

Treatment is symptomatic.

Drug Interactions

Cases of incompatibility with other drugs have not been registered to date.

Storage Conditions

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

Shelf Life

The shelf life is 3 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed 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.