Enterol forte

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ENTEROL FORTE

Composition:

Active substance:

1 sachet contains Saccharomyces boulardii CNCM I-745 500 mg (corresponding to 565 mg of lyophilized cells);

Excipients: lactose monohydrate; fructose; colloidal anhydrous silicon dioxide; flavouring "tutti frutti" (containing sorbitol E 420).

Pharmaceutical form. Powder for oral suspension.

Main physicochemical characteristics: sachet containing a very light brown powder.

Pharmacotherapeutic group. Antidiarrheal microbial agents. Saccharomyces boulardii. ATC code: A07FA02.

Pharmacological Properties

Pharmacodynamics

During passage through the gastrointestinal tract, Saccharomyces boulardii exerts a biological protective effect on the normal intestinal microflora.

Pharmacodynamic studies in vitro and in vivo, conducted in animals and humans, have confirmed that live probiotic cultures of Saccharomyces boulardii exhibit the following activities:

• Anti-inflammatory (against enterohemorrhagic strains of E. coli),
• Antimicrobial (against enterohemorrhagic strains of E. coli, C. difficile, S. typhimurium, Yersinia enterocolitica, C. albicans, C. krusei, C. pseudotropicalis),
• Enzymatic (disaccharidases, leucyl aminopeptidase, spermine, spermidine),
• Metabolic,
• Neutralizing activity against bacterial toxins (toxin A – C. difficile; cholera toxin),
• Immunostimulatory (increased secretion of IgA-class antibodies and other immunoglobulins).

These properties are beneficial and effective when Saccharomyces boulardii is administered to humans for the treatment of diarrhea of various etiologies (viral, bacterial, etc.).

Pharmacokinetics

Analysis of the fecal elimination kinetics of live S. boulardii cells following multiple doses of Saccharomyces boulardii at 1 g/day in healthy adult volunteers demonstrated that a steady state is reached by the third day of treatment. S. boulardii are rapidly eliminated in feces. No live Saccharomyces boulardii cells are detected in feces 2–5 days after discontinuation of the treatment.

There is a linear relationship between the amount of S. boulardii in feces and the administered dose. Concomitant administration of the antibiotic ampicillin, which is active against most anaerobic intestinal flora, doubles the amount of S. boulardii in feces. In clinical studies involving patients with recurrent C. difficile infection receiving S. boulardii at a dose of 1 g/day, the number of live yeast cells in feces was lower compared to patients without recurrent infection.

Non-clinical Safety Data

Studies in rats, mice, rabbits, and dogs evaluating acute and chronic toxicity, including at high doses, showed no adverse effects. The Ames test revealed no mutagenic activity. There are no data available regarding effects on reproductive function.

Clinical characteristics.

Indications.

The medicinal product Enterol Forte is indicated for use in adults for the prevention and treatment of diarrhea of various origins, namely:

• acute infectious diarrhea (bacterial or viral),
• diarrhea associated with the use of antibiotics and colitis,
• gastrointestinal adverse reactions during eradication of Helicobacter pylori,
• recurrent diarrhea caused by Clostridium difficile infection, as an adjunctive treatment to vancomycin and metronidazole.

Contraindications.

Hypersensitivity to any component of the product.

The product is contraindicated in patients with established central or peripheral venous catheters; critically ill patients and immunocompromised patients due to the risk of fungaemia (see section "Special precautions"); patients receiving treatment in intensive care units; immunocompromised patients, such as HIV-infected individuals, oncology patients, organ transplant recipients, patients undergoing chemotherapy and/or radiotherapy, and/or receiving prolonged high-dose corticosteroids.

The medicinal product must not be administered to individuals with allergy to yeast, particularly to Saccharomyces boulardii.

Interaction with other medicinal products and other types of interactions.

The medicinal product should not be administered concurrently with oral or intravenous antifungal agents, because Saccharomyces boulardii CNCM I-745 contained in the product are lyophilized yeast cells. No other interactions are expected.

Special precautions for use.

Special warnings

Diarrhoea may be a symptom of another, more serious condition. If diarrhoea persists for more than 2 days, if blood appears in the stool, or if fever develops, the patient should consult a physician to re-evaluate previous treatment and adjust oral rehydration or consider the need for parenteral rehydration. After diarrhoea has ceased, treatment may be continued for several more days. Treatment with this medicinal product does not replace fluid replacement (rehydration) when this is necessary. The amount of fluid for rehydration and the method of administration (oral or intravenous) should be determined according to the severity of diarrhoea symptoms, age, and the patient's general health status.

Very rare cases of fungaemia (with Saccharomyces strains isolated from blood) and sepsis, usually presenting with fever, have been reported, most commonly in patients with a central venous catheter or those with significantly impaired immunity.

In most cases, the outcome was favourable after discontinuation of Saccharomyces boulardii treatment and initiation of antifungal therapy, and, if necessary, removal of the catheter. In some critically ill patients, fungaemia resulted in death. (See sections "Contraindications" and "Side effects").

As with all medicinal products containing live microorganisms, special care should be taken when preparing the product in the presence of patients, particularly those with a central or peripheral venous catheter, and patients not receiving treatment with Saccharomyces boulardii, to prevent any risk of contamination via hands and/or airborne transmission of microorganisms (see section "Special precautions for use").

Excipients with known properties

This medicinal product contains lactose monohydrate and therefore should not be administered to patients with rare hereditary problems of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption.

The medicinal product contains fructose; therefore, patients with hereditary fructose intolerance should not take this medicinal product.

Each sachet contains 65 mg of lactose monohydrate and 943.8 mg of fructose.

Each sachet of the medicinal product contains 0.10 mg of sorbitol.

Precautions for use

Patients should be informed of the need to:

• perform rehydration (adequate fluid replacement) to compensate for fluid loss caused by diarrhoea (the average daily water requirement for an adult is 2 litres);
• follow an appropriate diet excluding certain foods such as fruits, raw vegetables, spicy foods, frozen foods, and cold beverages; however, baked meat and rice are recommended.

Reduction in the consumption of milk and dairy products should also be considered.

Enterol Forte contains living cells that grow at 37 °C. Therefore, this medicinal product must not be mixed with liquids, drinks, or food that are too hot (temperature above 50 °C), frozen, or contain alcohol.

Use during pregnancy or breastfeeding.

Pregnancy

Studies on toxic effects on reproductive function in animals are insufficient.

No congenital malformations or embryotoxic effects of Saccharomyces boulardii have been reported to date. However, available data on the use of Saccharomyces boulardii during pregnancy are insufficient to exclude risk. Saccharomyces boulardii CNCM I-745 are not absorbed. As a precautionary measure, the use of Enterol Forte during pregnancy is not recommended.

Breastfeeding

Saccharomyces boulardii are not absorbed into breast milk. Since adequate data are lacking, the benefit-risk balance should be assessed before taking Enterol Forte during breastfeeding.

Ability to influence the speed of reactions when driving or operating machinery.

The medicinal product Enterol Forte does not affect the ability to drive or operate machinery.

Dosage and Administration

The medicinal product Enterol Forte is intended for adults.

Acute infectious diarrhea (bacterial or viral): 1–2 sachets daily for up to 1 week.

Diarrhea associated with antibiotic use and colitis: 1–2 sachets daily during and after antibiotic treatment.

Gastrointestinal adverse reactions during H. pylori eradication: 1–2 sachets daily.

Diarrhea associated with C. difficile: 2 sachets daily for up to 4 weeks.

Administration method

The medicinal product is intended for oral use.

The contents of the sachet should be mixed with a small amount of water or sweetened beverage, stirred, and taken immediately. The powder from the sachet may also be mixed with food.

Water or food must not be too hot.

Due to the risk of airborne contamination, the sachet containing the powder should not be opened to prepare an oral solution in patient rooms. Healthcare personnel/doctors should wear gloves when preparing probiotics for patients, immediately dispose of the sachet after use, and thoroughly wash their hands afterward (see section "Special precautions for use").

Children

The medicinal product is not intended for use in children.

Pediatric patients should be treated with an appropriate dosage form and strength—Enterol 250, powder for oral use or capsules.

Overdose

Saccharomyces boulardii is not absorbed systemically; therefore, overdose is not expected. In case of overdose, no specific measures are required.

Adverse Reactions

The frequency of adverse reactions is defined as follows: very common (> 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000, including isolated cases), frequency not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are listed in order of decreasing severity.

Reporting of suspected adverse reactions

Reporting of adverse reactions after registration of a medicinal product is of great importance. It enables continuous monitoring of the benefit-risk balance of the use of this medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all cases of suspected adverse reactions and lack of efficacy of the medicinal product through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua/.

Shelf life.

3 years.

Storage conditions.

This medicinal product does not require special storage conditions.

Keep out of reach of children.

Packaging.

1 sachet containing powder, labelled in Ukrainian.

10 sachets in a cardboard box, labelled in Ukrainian.

Category of supply. Over-the-counter.

Manufacturer.

BIOCODEX.

Manufacturer's location and address of place of business.

Manufacturing address: 1 Avenue Blaise Pascal, 60000 Beauvais, France.