Enterogermina

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ENTEROGERMINA®

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: microcrystalline cellulose, light kaolin, xylitol, colloidal anhydrous silicon dioxide, citrus flavoring (containing natural flavorings, maltodextrin (corn), gum arabic (E 414), sorbitol (E 420), butylated hydroxyanisole (E320)).

Pharmaceutical form. Powder for oral administration.

Main physicochemical characteristics: fine-dispersed powder of yellowish-white color.

Pharmacotherapeutic group. Antidiarrheal microbial agents.

ATC code A07F A.

Pharmacological properties.

Pharmacodynamics.

Enterogermina® is a preparation containing a mixture of spores of 4 strains (SIN, O/C, T, N/R) of Bacillus clausii, which are normally present in the intestine and do not exhibit pathogenic activity.

Spores are inherently capable of withstanding high temperatures and gastric acidity. In a validated in vitro model, Bacillus clausii spores demonstrated the ability to survive in an environment simulating gastric conditions (pH 1.4–1.5) for up to 120 minutes (survival rate 96%). In a model simulating intestinal conditions (bile salt solution and pancreatin – pH 8), Bacillus clausii spores demonstrated the ability to multiply significantly compared to the initial count (from 10⁹ to 10¹² colony-forming units (CFU)), starting from 240 minutes after incubation.

In a study involving 20 subjects, it was observed that Bacillus clausii spores persist in the human intestine and can be detected in feces for up to 12 days after a single oral dose.

Due to the action of Bacillus clausii, the preparation restores intestinal microflora altered by drug therapy leading to dysbacteriosis (also known as dysbiosis), which may be associated with gastrointestinal symptoms such as diarrhea, abdominal pain, and meteorism (intestinal bloating). Furthermore, due to the ability of Bacillus clausii to synthesize various vitamins, particularly those of the B group, the preparation helps correct vitamin deficiencies caused by the use of antibiotics or chemotherapeutic agents. Thanks to the metabolic activity of Bacillus clausii, administration of the preparation achieves nonspecific antigenic and antitoxic effects.

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, the medicinal product Enterogermina® demonstrated a reduction in the duration of acute diarrhea in children aged 6 months and older.

When administered during antibiotic treatment and for the subsequent 7–10 days, Enterogermina® demonstrated a reduction in the frequency of antibiotic-associated abdominal pain and diarrhea. The two main properties of Bacillus clausii described below contribute to the restoration of 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 involving spores in the initial 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 including Staphylococcus aureus, Clostridium difficile, and Enterococcus faecium.

Immunomodulatory activity

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

Pharmacokinetics.

No data available.

Clinical characteristics.

Indications.

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

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. Pediatric age.

Special precautions.

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

The product has a high degree of heterologous resistance to antibiotics, allowing its use both for prevention 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.

If the product is prescribed simultaneously with antibiotics, it should be administered between two doses of the antibiotic.

Interaction with other medicinal products and other forms of interaction.

There is no data available on interactions of this product with other medicinal products.

Special precautions for use

Xylitol contained in the medicinal product may have a laxative effect. The energy value of 1 g of xylitol is 2.4 kcal. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product due to the presence of sorbitol.

Bacteraemia and sepsis

During post-marketing use, cases of bacteraemia, septicaemia and sepsis have been observed in patients with weakened immune systems, critically ill patients, as well as in premature infants. In some severely ill patients, the outcome was fatal. This medicinal product should be avoided in these patient groups (see section "Adverse reactions").

Use during pregnancy or breastfeeding

Pregnancy. Available data on the use of Enterogermina® in pregnant women are limited; therefore, no conclusion can be drawn regarding the safety of the product during pregnancy.

Enterogermina® may be used during pregnancy only if the potential benefit to the pregnant woman outweighs the potential risks, including risks to the fetus.

Breastfeeding. Available data on the use of Enterogermina® during lactation, particularly regarding the presence of the product in breast milk and its effects on the infant, are limited; therefore, no conclusions can be drawn regarding the safety of the product during breastfeeding.

Enterogermina® may be used during breastfeeding only if the potential benefit to the mother outweighs the potential risks, including risks to the breastfed infant.

Fertility. There are no data available on the effect of Enterogermina® on human fertility.

Ability to affect reaction speed when driving or operating machinery

Enterogermina® does not affect the ability to drive or operate machinery.

Dosage and Administration.

Adults: 1 sachet per day.

The powder may be dissolved directly in the mouth by saliva; it does not need to be taken with water or other liquids.

This medication is intended for oral use only.

The duration of treatment is determined by the physician depending on the patient's condition and course of the disease.

Children. This medication is not intended for use in children.

Overdose.

There have been no reports of clinical manifestations of overdose with this medication to date.

Adverse reactions.

The adverse reactions observed during the use of Enterogermina® are listed below according to system organ classifications and frequency of occurrence: very common (> 1/10); common (> 1/100, < 1/10); uncommon (> 1/1000, < 1/100); rare (> 1/10 000, < 1/1000); very rare (< 1/10 000); frequency not known (cannot be estimated from available data).

Disorders of the skin and subcutaneous tissue

Frequency not known: hypersensitivity reactions, including rash, urticaria, and angioedema.

Infectious and parasitic disorders

Frequency not known: bacteremia, septicemia, and sepsis (in patients with weakened immunity or critically ill patients) (see section "Special precautions for use").

Reporting suspected adverse reactions

It is important to report suspected adverse reactions after marketing authorization of the medicinal product, as this allows continuous monitoring of the benefit-risk balance of the drug. Healthcare professionals are encouraged to report any suspected adverse reactions through the national pharmacovigilance system.

Shelf life. 3 years.

Storage conditions.

Keep out of reach and sight of children. Store below 30 °C.

Packaging.

Sachets of 9, 12, 18, 24: 2 g per sachet, 9, 12, 18 or 24 sachets per cardboard box.

Availability. Over-the-counter.

Manufacturer.

Opella Healthca Italia S.r.l.

Manufacturer's address and location of operations.

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

Marketing Authorization Holder.

LLC "Opella Healthca Ukraine".

Address of the Marketing Authorization Holder.

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