Instructions for use Mutaflor gastro-resistant capsules blister No. 20
Composition
active ingredient: Escherichia coli strain NISSLE 1917;
composition per 1 unit of dosage form:
Escherichia coli strain NISSLE 1917 – 2.5 – 25x109 live bacterial cells (colony-forming units, CFU);
excipients: maltodextrin, talc, copolymer (1:1) of methacrylic acid - methyl methacrylate, macrogol (4000), triethyl citrate, glycerol 85%, titanium dioxide (E 171), red iron oxide (E 172), gelatin, yellow wax, carnauba wax, shellac, purified water.
Dosage form
Gastro-resistant, hard capsules.
Main physicochemical properties: colorless, transparent, cylindrical hard capsules in a red-brown gastro-resistant shell. The contents of the capsule are a light beige powder with a characteristic odor. The surface of the capsule is smooth, without cracks.
Pharmacotherapeutic group
Antidiarrheal, intestinal anti-inflammatory and anti-infective drugs.
Intestinal anti-inflammatory drugs. ATX code A07E.
Pharmacological properties
Pharmacodynamics
The active substance is a strain of non-pathogenic bacteria of human origin belonging to the species Escherichia coli (E. coli), in a live and capable of reproduction form: E. coli strain NISSLE 1917. With the help of special adhesive organelles (type F-1A, F-1C and "curly" fimbriae), the strain has the ability to attach to the mucosa of the colon and form microcolonies in the form of a biofilm. Due to the presence of flagella, bacteria are inherently mobile, which gives them an advantage when colonizing the colon. The effects of the drug MUTAFLOR (E. coli strain NISSLE 1917) were determined in in vitro and in vivo experiments, as well as in clinical studies.
Antimicrobial properties (antagonism): E. coli strain NISSLE 1917 forms antimicrobial substances (microcins) and numerous iron-binding systems (siderophores), which, on the one hand, are responsible for direct antagonism against pathogens, as well as for the resistance of the strain, the duration of which exceeds the duration of oral administration of the drug itself. In addition, the strain has an inhibitory effect on the invasion of enteroinvasive pathogens into the mucosa of the large intestine.
Stabilization of the mucosal barrier in the colon. In experiments on cell cultures of colonic epithelial cells, E. coli strain NISSLE 1917 demonstrated the ability to stabilize the barrier function of the epithelium and normalize the increased permeability of the intestinal mucosa in general. Such strengthening of the barrier function is a consequence of stimulation of the synthesis of the fixing protein (ZO-2) and the formation of strong intercellular contacts with its help.
Immunostimulating properties:
Effect on humoral immune response
In humans, after colonisation of the intestine with E. coli strain NISSLE 1917, a significant increase in IgA and IgM levels was observed in the fecal filtrate and serum. In rare cases, an increase in IgA levels in saliva has been described. In animals, oral administration of E. coli strain NISSLE 1917 to sterile (without existing microflora) newborn offspring stimulated the development of immunocompetent cells of the intestinal immune system (IgA- and IgG-producing lymphocytes, cells expressing proteins of the major histocompatibility complex class II (MHC-II) on their surface) without any signs of inflammation (no granulocyte migration).
Impact on cellular immune response
In vitro studies have revealed immunomodulatory properties of E. coli strain NISSLE 1917. Thus, an increase in the secretory activity of mouse macrophages (interleukin-6 [IL-6], tumor necrosis factor, oxygen radicals) and human peripheral blood mononuclear cells (interleukin-10) was found. However, an increase in the level of tumor necrosis factor secretion was not confirmed in in vivo studies in mice and other animals.
In addition, an increase in the cytotoxic properties of mouse macrophages directed against intracellular parasites, and therefore a stronger protection against intracellular infectious agents, was demonstrated ex vivo.
Escherichia coli strain NISSLE 1917 also caused inhibitory effects on the cell cycle and proliferation of human T lymphocytes in peripheral blood, but not on intestinal T lymphocytes.
Therefore, in inflammatory bowel diseases, the migration of new activated T lymphocytes into the focus of inflammation can be prevented in this way.
Impact on innate immunity
E. coli strain NISSLE 1917 stimulates the synthesis of antimicrobial peptides. In particular, it stimulates the production of defensins by human colon epithelial cells in vitro, as well as calprotectin in vivo in the intestine of sterile newborn animal offspring after oral administration of the drug. In humans, oral administration of the drug MUTAFLOR also positively affects the innate and adaptive immune response in newborn (premature) infants.
Anti-inflammatory properties. MUTAFLOR has an anti-inflammatory effect. The anti-inflammatory properties of E. coli strain NISSLE 1917 were discovered in in vitro experiments with human epithelial cells, as well as in vivo.
Effect on metabolism. The strain contained in the preparation MUTAFLOR is involved in numerous metabolic processes and is able to catabolize various carbohydrates, sugar alcohols, amino acids and other substrates, consuming oxygen. The anaerobic environment in the lumen of the colon, created in this way, is maintained for a long time, which is extremely important for the stability of the intestinal ecosystem.
Pharmacokinetics
Due to their shell, MUTAFLOR capsules are resistant to the action of gastric juice and do not dissolve until the terminal part of the small intestine. Since the active substance (E. coli strain NISSLE 1917) is a commensal, it quickly colonizes the large intestine without being absorbed or metabolized, and leaves the intestine with feces.
Indication
Chronic constipation. Nonspecific ulcerative colitis in remission.
Contraindication
Hypersensitivity to the ingredients of the drug.
Interaction with other medicinal products and other types of interactions
Antibiotics prescribed to affect gram-negative bacteria, as well as sulfonamides, may reduce the effectiveness of MUTAFLOR.
Application features
None.
Ability to influence reaction speed when driving vehicles or other mechanisms
Not detected.
Use during pregnancy or breastfeeding
Escherichia coli strain NISSLE 1917 is a commensal bacterium that is present in the human intestine and is not absorbed, does not affect fertility, the course of pregnancy and the period of breastfeeding, therefore there are no precautions for use.
Method of administration and doses
The entire daily dose should be taken during a meal, preferably during breakfast, with sufficient liquid. Do not chew the capsules.
If abdominal bloating develops or if an initial dose higher than the standard recommended dose is taken, the daily dose may be divided between all daily meals.
Adults and teenagers.
Standard dose: from the first to the fourth day of administration – 1 capsule of MUTAFLOR per day, then – 2 capsules of MUTAFLOR per day.
In case of prolonged constipation, the dose can be increased to 4 capsules of MUTAFLOR daily.
In ulcerative colitis. Experience with the use of the drug for 12 months in ulcerative colitis is based on the results of controlled studies. To prevent relapses of ulcerative colitis, MUTAFLOR should be taken continuously.
For chronic constipation. MUTAFLOR can be taken for 6 weeks. If the disease has been present for many years, MUTAFLOR can be considered as a general tonic, and therefore therapy with its use should be repeated periodically.
Children
Apply to children over 15 years of age.
Overdose
There is no data on overdose of the drug.
Adverse reactions
The drug is well tolerated. Adverse reactions are classified according to the following frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), including isolated reports.
Gastrointestinal: Common (≥1/100, <1/10) abdominal bloating at the beginning of therapy. Very rare (<1/10,000) changes in stool consistency or frequency, abdominal pain, flatulence, diarrhea, abdominal rumbling, nausea or vomiting.
Skin: very rare (<1/10,000) rash, erythema and peeling of the skin, allergic reactions.
From the side of the central nervous system: there are isolated reports of headache.
Expiration date
12 months.
Storage conditions
Store at a temperature of 2 - 8 ° C in places inaccessible to children.
Do not use after the expiry date stated on the packaging.
Packaging
2 blisters of 10 capsules in a cardboard box.
Vacation category
According to the recipe.
Producer
Ardeypharm GmbH / Ardeypharm GmbH.
Location of the manufacturer and its business address
Loerfeldstrasse 20, 58313 Herdecke, Germany.
