Enterogermina®

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

Composition:

Active substance: spores of the polyresistant strain Bacillus clausii;

1 sachet of 2 g contains spores of the polyresistant strain Bacillus clausii 6 × 10⁹;

Excipients: heavy kaolin, microcrystalline cellulose, mannite (E 421), sodium saccharin, citrus flavoring, colloidal anhydrous silicon dioxide.

Pharmaceutical form. Powder for oral suspension.

Main physico-chemical characteristics: fine-dispersed powder ranging in color from whitish to ivory.

Pharmacotherapeutic group. Anti-diarrheal microbial agents.

ATC code A07FA.

Pharmacological properties.

Pharmacodynamics.

Enterogermina® is a powder for oral suspension containing spores of 4 strains (SIN, O/C, T, N/R) of Bacillus clausii, normally present in the intestine and non-pathogenic.

Spores are inherently resistant to high temperatures and gastric acidity. In a validated in vitro model, Bacillus clausii spores demonstrated the ability to survive in a simulated gastric environment (pH 1.4–1.5) for up to 120 minutes (survival rate 96%). In a model simulating intestinal conditions (bile salts and pancreatin solution – pH 8), Bacillus clausii spores showed the ability to multiply significantly compared to the initial count (from 10^9 to 10^12 CFU – colony-forming units), starting from 240 minutes after incubation. In a study conducted in 20 individuals, Bacillus clausii spores were consistently detected in feces up to 12 days after a single oral dose.

Due to the action of Bacillus clausii, the medicinal product restores intestinal microflora altered by treatments causing dysbacteriosis (also known as dysbiosis), which may be associated with gastrointestinal symptoms such as diarrhea, abdominal pain, and increased intestinal gas. Furthermore, due to the ability of Bacillus clausii to synthesize various vitamins, particularly those of the B group, the product helps correct vitamin deficiencies caused by antibiotics or chemotherapeutic agents. Thanks to the metabolic activity of Bacillus clausii, the product exerts a non-specific antigenic and antitoxic effect.

Due to the high resistance of Bacillus clausii spores to chemical and physical agents, they pass unharmed through the gastric juice barrier into the intestinal tract, where they transform into metabolically active vegetative cells.

In two open, randomized, controlled clinical trials, Enterogermina® demonstrated a reduction in the duration of acute diarrhea in children over 6 months of age.

When administered during antibiotic therapy and for the subsequent 7–10 days, Enterogermina® demonstrated a reduction in the frequency of antibiotic-associated abdominal pain and diarrhea.

The two main mechanisms described below contribute to the effect of Bacillus clausii in restoring intestinal bacterial flora.

Inhibition of pathogenic bacterial growth

Three likely mechanisms of action of B. clausii are: colonization of free ecological niches, thereby preventing the growth of other microorganisms; competition for binding to epithelial cells, particularly relevant for spores in the early and intermediate phases of germination; and production of antibiotics and/or enzymes secreted into the intestinal environment. In an in vitro study, Bacillus clausii spores demonstrated the production of bacteriocins and antibiotics such as clausin, with antagonistic activity against gram-positive bacteria Staphylococcus aureus, Clostridium difficile, Enterococcus faecium.

Immunomodulatory activity

Orally administered Bacillus clausii spores demonstrated stimulation of interferon-gamma production and increased proliferation of CD4+ T-lymphocytes in in vitro and in vivo mouse models.

Pharmacokinetics.

No data available.

Clinical characteristics.

Indications.

Treatment and prevention of intestinal dysbacteriosis and associated endogenous vitamin deficiency.

Adjunctive therapy aimed at restoring normal intestinal microflora disrupted during treatment with antibiotics or chemotherapeutic agents.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients of the medicinal product.

Paediatric use.

Special precautions.

The medicinal product has a high degree of heterologous resistance to antibiotics, allowing its use both for prophylaxis of intestinal microflora alterations caused by the selective action of antibiotics (especially broad-spectrum antibiotics) and for restoration of already disrupted intestinal microflora balance.

The medicinal product does not interact with the following antibiotics: penicillin when used without beta-lactamase inhibitors, cephalosporins (partial resistance in most cases), tetracyclines, macrolides, aminoglycosides (except gentamicin and amikacin), chloramphenicol, thiamphenicol, lincomycin, clindamycin, isoniazid, cycloserine, novobiocin, rifampicin, nalidixic acid and pipemidic acid (intermediate resistance), metronidazole.

During antibiotic therapy, it is recommended to administer the medicinal product between doses of antibiotics.

This medicinal product is intended for oral use only. The product must not be administered by injection or any other route. Incorrect administration of this medicinal product has led to severe anaphylactic reactions, including anaphylactic shock.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e. it is practically sodium-free.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

Features of use.

Use during pregnancy or breastfeeding.

There are no contraindications for the use of the drug during pregnancy or breastfeeding.

Fertility

Data on the effect of Enterogermina® powder for oral suspension on human fertility are lacking.

Ability to influence reaction rate when driving or operating machinery.

Enterogermina® does not affect the ability to drive vehicles or operate machinery, or the effect is negligible.

Method of Administration and Dosage.

Adults: 2 g (1 sachet) per day. The contents of the sachet should be dissolved in water and taken immediately.

This medication is intended for oral use only.

The duration of treatment is determined individually by a physician.

Children. The medication is not intended for use in children (see section "Contraindications").

Overdose.

No cases of overdose have been reported.

Side effects.

Disorders of the skin and subcutaneous tissues

Frequency unknown: hypersensitivity reactions, including rash and urticaria, angioedema.

Infectious and parasitic diseases

Frequency unknown: bacteremia (in patients with weakened immunity).

Reporting of suspected adverse reactions.

It is very important to report suspected adverse reactions that occur after the drug has been registered, as this enables continuous monitoring of the benefit-risk balance of this medicinal product. Healthcare professionals are obliged to report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life. 3 years.

Storage conditions.

Keep out of the reach of children at a temperature below 30 °C.

Packaging.

No. 10 (2 × 5): 2 g in sachets; 10 sachets (each 2 sachets separated by a dotted line) in a cardboard box.

Supply classification. Over-the-counter.

Manufacturer.

Opella Helthea Italia S.r.l.

Manufacturer's location and address of the place of business.

Viale Europa, 11 – 21040 Origgio (VA), Italy.

Marketing Authorization Holder.

LLC "Opella Helthea Ukraine", Ukraine.

Location and address of the Marketing Authorization Holder.

Ukraine, 01033, Kyiv, Zhilyanska St., 48-50A.