Alpha Normix tab ppo 200mg No. 12

Pharmacological properties of the drug Alpha Normix

Pharmacodynamics. Rifaximin is a broad-spectrum antibiotic and is a semi-synthetic derivative of rifamycin SV. Irreversibly binds the β-subunits of the bacterial enzyme, DNA-dependent RNA polymerase and, therefore, inhibits the synthesis of RNA and bacterial proteins. As a result of irreversible binding to the enzyme, rifaximin exhibits bactericidal properties against sensitive bacteria. The drug has a wide spectrum of antibacterial activity, including most gram-negative and gram-positive, aerobic and anaerobic bacteria that cause gastrointestinal infections, including traveler's diarrhea. Gram-negative Aerobes: Salmonella spp., Shigella spp., Escherichia coli, including enteropathogenic strains, Proteus spp., Campylobacter spp., Pseudomonas spp., Yersinia spp., Enterobacter spp., Klebsiella spp., Helicobacter pylori ; anaerobes: Bacteroides spp., including Bacteroides fragilis, Fusobacterium nucleatum ; Gram-positive aerobes: Streptococcus spp., Enterococcus spp. , including Enterococcus fecalis, Staphylococcus spp. ; anaerobes: Clostridium spp. , including Clostridium difficile and Clostridium perfrigens, Peptostreptococcus spp. . Absorption of rifaximin in the α polymorphic form in the gastrointestinal tract when taken orally is insignificant (≤1%). The antibiotic acts locally in the intestine, where its high concentration is achieved, significantly higher than the minimum inhibitory concentration for the tested enteropathogenic microbes (after 3 days of therapy, a fecal level of 4000–8000 mcg/g is achieved when taking a daily dose of 800 mg). Due to this, rifaximin has a pronounced antibacterial effect. The use of the drug helps to reduce pathogenic intestinal bacterial flora, which causes some pathological conditions or is involved in their pathogenesis. The drug reduces:

• the formation by bacteria of ammonia and other toxic compounds, which in the case of severe liver disease, accompanied by a violation of the detoxification process, are involved in the pathogenesis of hepatic encephalopathy;
• increased proliferation of bacteria in intestinal microbial overgrowth syndrome;
• the presence of bacteria in the intestinal diverticulum, which may be involved in inflammation in and around the diverticulum and may play a key role in the development of symptoms and complications of diverticulosis;
• antigenic stimuli that, in the presence of genetically determined defects in mucosal immunoregulation and/or protective function, can induce or permanently maintain chronic intestinal inflammation;
• risk of infectious complications during colorectal surgery.

Due to the virtually absent absorption of rifaximin in the gastrointestinal tract, there is no risk of systemic side effects. In numerous clinical studies, rifaximin was always well tolerated by patients. Pharmacokinetics Rifaximin oral absorption is ≤1% based on pharmacokinetic studies in rats, dogs and humans. The drug is not detected in blood plasma after administration in therapeutic doses (detection limit ≤0.5–2 ng/ml) or is detected in very low concentrations (less than 10 ng/ml in almost all cases) both in healthy volunteers and in patients with damaged intestinal mucosa (as a result of ulcerative colitis or Crohn's disease). Rifaximin found in urine is no more than 0.5% of the dose taken orally. Almost all rifaximin taken orally is found in the gastrointestinal tract, where very high concentrations of the drug are achieved (concentrations in feces of 4000-8000 mcg/g are achieved after 3 days of taking the drug at a daily dose of 800 mg). Comparative pharmacokinetic studies have demonstrated that polymorphic forms of rifaximin are absorbed from the intestine in greater quantities than polymorphic form α.

Rifaximin

Rifaximin

(lat.
rifaximin
) - a broad-spectrum intestinal antibiotic. It is characterized by very low absorption in the gastrointestinal tract after oral administration, due to which it creates high concentrations of the drug in the intestinal lumen.

Rifaximin is a chemical substance

Rifaximin is a semi-synthetic derivative of rifamycin SV: 4-deoxy-methylpyrido[1, 2, -1,2] imidazo-[5, 4-c]rifamycin SV. Empirical formula: C43H51N3O11.

Rifaximin - medicine

Rifaximin is the international nonproprietary name (INN) of the drug. According to the pharmacological index, rifaximin belongs to the Ansamycin group, according to ATC:

• to the group “A07 Antidiarrheal drugs” and has the code A07AA11
• to the group “D06 Antibiotics and chemotherapeutic agents for the treatment of skin diseases”, code D06AX11

Rifaximin is an antibiotic

Rifaximin is active against the following bacteria:

• gram-negative
• aerobic and microaerophilic Helicobacter pylori, Campylobacter spp., Salmonella spp., Shigella spp.
  , pathogenic strains of
  Escherichia coli, Proteus spp., Pseudomonas spp., Yersinia spp., Enterobacter spp., Klebsiella spp.
• anaerobic: Bacteroides spp.
  , including
  Bacteroides fragilis, Fusobacterium nucleatum

• aerobic: Streptococcus spp., Enterococcus spp
  ., including
  Enterococcus faecalis, Staphylococcus spp.
• anaerobic: Clostridium spp.
  , including
  Clostridium difficile
  and
  Clostridium perfrigens, Peptostreptococcus spp
  .

Indications for use of rifaximin

Indications for the use of rifaximin are infections of the gastrointestinal tract caused by pathogens sensitive to rifaximin listed in the previous section, including:

• acute infections
• traveler's diarrhea
• syndrome of bacterial overgrowth of microorganisms in the intestines
• hepatic encephalopathy
• symptomatic uncomplicated colonic diverticulosis
• chronic colitis

Rifaximin is used to prevent infectious complications during colorectal surgery. Rifaximin is FDA approved in the United States for the treatment of traveler's diarrhea caused by Escherichia coli.
On May 27, 2015, the FDA also approved rifaximin (trade name Xifaxan) for the treatment of irritable bowel syndrome (IBS) with diarrhea in adults.

Rifaximin is moderately effective in preventing traveler's diarrhea in tourists visiting countries in South and Southeast Asia.

Methods of using rifaximin and dosage

Rifaximin is taken orally.
Children over 12 years of age and adults - 200 mg every 8 hours or 400 mg every 8-12 hours. Doses and regimen can be adjusted by your doctor. The duration of rifaximin therapy is no longer than 7 days and is determined by the condition of the patients. A repeated course of treatment is carried out no earlier than after 20–40 days. For the treatment of irritable bowel syndrome with pain, rifaximin is recommended to take one tablet (200 mg) three times a day for 14 days. The course can be repeated 1-2 times.

Rifaximin at a dose of 800 mg/day for 7 days is effective in correcting moderate to severe overgrowth syndrome (SIBO) (Loginov V.A.).

Rifaximin in Helicobacter pylori eradication regimens

Rifaximin is not listed by the WHO in the list of drugs active against Helicobacter pylori
(Podgorbunskikh E.I., Maev I.V., Isakov V.A.) and is not mentioned in the so-called Maastricht consensus (Lapina T.L.).
However, based on the high resistance of the Russian population to metronidazole and some other antibiotics, the Russian Standards for the diagnosis and treatment of acid-dependent and Helicobacter pylori-associated diseases (2010) recommend rifaximin in one of their “second-line” regimens (used only if the patient had an unsuccessful attempt at eradication Helicobacter pylori
according to one of the “first line” schemes):

• one of the standard dosage proton pump inhibitors (omeprazole 20 mg, lansoprazole 30 mg, pantoprazole 40 mg, esomeprazole 20 mg or rabeprazole 20 mg twice a day), amoxicillin (500 mg 4 times a day or 1000 mg twice a day) , rifaximin (400 mg 2 times a day), tripotassium bismuth dicitrate (120 mg 4 times a day) for 14 days.

Rifaximin in the treatment of bacterial overgrowth syndrome in patients with postcholecystectomy syndrome

In a study conducted at the Central Research Institute of Gastroenterology (Mechetina T.A. et al.) it was found that in patients with postcholecystectomy syndrome and bacterial overgrowth syndrome (BOS) who took rifaximin at a dose of 800 mg per day, pain decreased in 35%, flatulence - in 75%, diarrhea in 60%). When compared with patients taking rifaximin at a dose of 1200 mg per day, it was revealed that on the 8th day of observation, these patients had no complaints in most cases: pain disappeared in 60%, flatulence in 90%, diarrhea in 75% ( Fig. 1). Thus, a weekly course of treatment with rifaximin is accompanied by positive dynamics in the form of a decrease in the intensity of clinical symptoms of SIBO and normalization or reduction of hydrogen breath test values. In this case, a more pronounced effect is observed with increasing doses of the drug.

Rice. 1. Dynamics of clinical symptoms before and after rifaximin therapy (Mechetina T.A. et al.)

Weekly therapy with rifaximin has a prolonged effect. Thus, on the 30th day of observation in the group of patients taking rifaximin at a dose of 800 mg per day, the clinical symptoms of SIBO disappeared in most of them: pain was absent in 55% of patients, flatulence in 70%, diarrhea in 75%. However, in some patients they persisted, despite a decrease in their severity. When compared with patients who received rifaximin at a higher dose, it was revealed that among them there was a significantly larger number of patients with no complaints. Thus, there was no pain in 85%, flatulence in 90%, diarrhea in 95% (Fig. 2).

Rice. 2. Dynamics of clinical symptoms before and 1 month after rifaximin therapy (Mechetina T.A. et al.)

Professional medical articles regarding the use of rifaximin in the eradication of Helicobacter pylori and bacterial overgrowth syndrome

• Karimov M.M., Saatov Z.Z., Spiridonova A.Yu., Akhmatkhodzhaev A.M. The use of alpha normix in a complex of eradication therapy in patients with duodenal ulcer.
• Loginov V.A. Bacterial overgrowth syndrome in patients with reduced acid-producing function of the stomach. Abstract of dissertation. Ph.D., 01/14/04 – ext. diseases. UMTS UDPRF, Moscow, 2015.
• Mechetina T.A., Bystrovskaya E.V., Ilchenko A.A. Rationale for identifying the clinical variant of postcholecystectomy syndrome associated with excessive bacterial growth in the small intestine // Experimental and clinical gastroenterology. 2011. No. 4. pp. 37–43.

On the website gastroscan.ru in the literature catalog there is a section “Antibiotics used in the treatment of gastrointestinal diseases”, containing articles on the use of antimicrobial agents in the treatment of diseases of the digestive tract.

Use of rifaximin during pregnancy and breastfeeding

Pregnant women should only take rifaximin when absolutely necessary and under the direct supervision of a doctor. While taking rifaximin, breastfeeding should be temporarily stopped. The FDA category of action of rifaximin on the fetus is C.

Side effects of rifaximin therapy

The most common side effects when taking rifaximin are nausea and an increase in alanine aminotransferase (liver enzyme) in the blood.
The latter may indicate a damaging effect of rifaximin on the liver. If, after a course of rifaximin therapy for IBS with diarrhea, stool does not improve or even worsens, it is necessary to analyze the patient's condition regarding the presence of infectious diarrhea, Clostridium difficile

-associated enterocolitis.

Trade names of drugs containing the active ingredient rifaximin

Only Alpha Normix is ​​registered in Russia.
In the United States, rifaximin is sold under the brand name Xifaxan. On the European market - under the trade names Spiraxin, Zaxine, Normix, Rifacol and Colidur. Rifaximin has contraindications, side effects and application features; consultation with a specialist is necessary.

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Use of the drug Alpha Normix

Suspension Adults and children over 12 years of age: 10 ml oral suspension 3 times daily to 20 ml oral suspension 2–3 times daily (600–1200 mg rifaximin). Children aged 6 to 12 years: 10 ml oral suspension 2–3 times daily to 20 ml oral suspension 2 times daily (400–800 mg rifaximin). Children aged 2 to 6 years: 5 ml oral suspension 2-3 times daily to 10 ml oral suspension 3 times daily (200-600 mg rifaximin). For the treatment of adults and children over 6 years of age, instead of an oral suspension, Alpha Normix can be used in the form of film-coated tablets, 200 mg each. Tablets Adults and children over 12 years of age: from 1 tablet 3 times a day to 2 tablets 2-3 times a day (600-1200 mg rifaximin). Children aged 6 to 12 years: from 1 tablet 2-3 times a day to 2 tablets 2 times a day (400-800 mg of rifaximin). The duration of treatment should not exceed 7 days and depends on the clinical effect in patients. If necessary, repeated courses of treatment can be carried out with a break of 20–40 days. The total duration of therapy depends on the adequacy of the clinical effect in patients. Doses and frequency of administration can be changed on the recommendation of a doctor. Preparation of the suspension The granules for the preparation of the oral suspension are in a hermetically sealed bottle. The bottle must be opened, water added to the mark and shaken well. Add water again until the slurry reaches the specified level. The concentration of rifaximin in the finished suspension is 100 mg per 5 ml. To measure 5, 10 or 15 ml of suspension, add a measuring cup. The suspension remains stable for 7 days at room temperature. Before taking the drug, the bottle must be shaken well.

Alpha Normix tab ppo 200mg No. 12

Compound

Active substance: rifaximin (with polymorphic structure alpha) - 200 mg. Excipients: sodium carboxymethyl starch - 15 mg, glyceryl palmitostearate - 18 mg, colloidal silicon dioxide - 1 mg, talc - 1 mg, microcrystalline cellulose - 115 mg.

Pharmacokinetics

Suction

Rifaximin in the alpha polymorphic form is practically not absorbed when taken orally (less than 1%). With repeated use in healthy volunteers and in patients with damaged intestinal mucosa, inflammatory bowel diseases, plasma concentrations are very low (less than 10 ng/ml). When using the drug 30 minutes after eating a fatty meal, an increase in the systemic absorption of rifaximin, which was not clinically significant, was noted.

Distribution

Rifaximin is moderately bound to plasma proteins. Protein binding in healthy volunteers is 67.5%, and in patients with liver failure 62%.

Removal

It is excreted unchanged from the body by the intestines (96.9% of the dose taken), because does not undergo degradation or metabolism when passing through the gastrointestinal tract. Rifaximin detected using labeled isotopes in urine is no more than 0.025% of the dose taken orally. Less than 0.01% of the dose is excreted by the kidneys as 25-desacetylrifaximin, the only metabolite of rifaximin identified in humans. Renal excretion of 14C rifaximin does not exceed 0.4%.

Systemic exposure is nonlinear and dose-dependent, which is comparable to the absorption of rifaximin, possibly limited by the rate of dissolution.

Pharmacokinetics in special groups of patients

There are no clinical data on the use of rifaximin in renal failure.

Systemic exposure in patients with liver failure exceeds that in healthy volunteers. The increased systemic exposure in these patients should be considered in light of the local action of rifaximin in the intestine and its low systemic bioavailability, as well as the available data on the safety of rifaximin in patients with cirrhosis.

The pharmacokinetics of rifaximin in children has not been studied.

Indications for use

Treatment of gastrointestinal infections caused by bacteria sensitive to rifaximin, including:

• acute gastrointestinal infections;
• traveler's diarrhea;
• syndrome of excessive growth of microorganisms in the intestines;
• with hepatic encephalopathy;
• with symptomatic uncomplicated diverticular disease of the colon;
• for chronic intestinal inflammation.

Prevention of infectious complications during colorectal surgery.

Contraindications

• diarrhea accompanied by fever and loose, bloody stools;
• intestinal obstruction (including partial);
• severe ulcerative lesions of the intestines;
• children under 12 years of age (efficacy and safety have not been established);
• hereditary fructose intolerance, impaired absorption of glucose-galactose, sucrase-isomaltase deficiency (for the dosage form of granules for the preparation of an oral suspension);
• hypersensitivity to rifaximin or other rifamycins or to any of the components included in the drug.

With caution: renal failure, concomitant use with oral contraceptives, concomitant use with a P-glycoprotein inhibitor such as cyclosporine.

Directions for use and doses

The drug is taken orally with a glass of water, regardless of meals.

When treating diarrhea, adults and children over 12 years of age are prescribed 200 mg (1 tablet or 10 ml of suspension) every 6 hours. Treatment of traveler's diarrhea should not exceed 3 days.

For hepatic encephalopathy, adults and children over 12 years of age are prescribed 400 mg (2 tablets or 20 ml suspension) every 8 hours.

To prevent postoperative complications during colorectal surgery, adults and children over 12 years of age are prescribed 400 mg (2 tablets or 20 ml of suspension) every 12 hours. Prevention is carried out 3 days before surgery.

For bacterial overgrowth syndrome, adults and children over 12 years of age are prescribed 400 mg (2 tablets) every 8-12 hours.

For symptomatic uncomplicated diverticulosis, adults and children over 12 years of age are prescribed 200-400 mg (1-2 tablets or 10 to 20 ml of suspension) every 8-12 hours.

For chronic inflammatory bowel diseases, adults and children over 12 years of age are prescribed 200-400 mg (1-2 tablets or 10 to 20 ml of suspension) every 8-12 hours.

The duration of treatment with Alpha Normix® should not exceed 7 days. A second course of treatment should be carried out no earlier than after 20-40 days. The total duration of treatment is determined by the clinical condition of the patients. On the recommendation of a doctor, the dose and frequency of administration may be changed.

Dose adjustment is not required in elderly patients and in patients with hepatic and renal insufficiency.

Rules for preparing the suspension

Granules for preparing a suspension for oral administration are in a hermetically sealed bottle. To prepare the suspension, you need to open the bottle, add water to the mark and shake the bottle well. Add water again until the suspension level reaches the indicated 60 ml mark.

The concentration of rifaximin in the prepared suspension is 100 mg per 5 ml. Shake the suspension well before use. The finished suspension should be measured using the measuring cup included in the package.

Storage conditions

Store out of the reach of children, at a temperature not exceeding 30°C.

Best before date

3 years. Do not use after the expiration date indicated on the package.

special instructions

Clinical data indicate that Alpha Normix® is ineffective in the treatment of intestinal infections caused by Campylobacter jejuni, Salmonella spp., Shigella spp., which cause frequent diarrhea, fever, and bloody stool. Alpha Normix® is not recommended for use if patients have fever and loose, bloody stools. Alpha Normix® should be discontinued if symptoms of diarrhea worsen or persist for more than 48 hours. Other antibacterial therapy should be prescribed. Treatment for traveler's diarrhea should not exceed 3 days.

It is known that Clostridium difficile-associated diarrhea can develop with the use of almost all antibacterial agents, including the drug Alpha Normix®. A potential relationship between Alpha Normix® and the development of Clostridium difficile-associated diarrhea and pseudomembranous colitis cannot be excluded. There is no experience with the use of rifaximin in combination with other rifamycins. Patients should be warned that, despite the slight absorption of rifaximin (less than 1%), it can cause urine to turn reddish in color: this is due to the active substance rifaximin, which, like most antibiotics of this series (rifamycins), has a reddish-orange color. If superinfection develops with microorganisms that are insensitive to rifaximin, taking Alpha Normix® should be stopped and appropriate therapy should be prescribed. Due to the effect of Alpha Normix® on the intestinal flora, the effectiveness of oral contraceptives containing estrogens may decrease after taking it. It is recommended to use additional contraceptive measures when taking Alpha Normix®, especially if the estrogen content of oral contraceptives is less than 50 mcg. Taking Alpha Normix® is possible no earlier than 2 hours after taking activated carbon. Granules for the preparation of an oral suspension contain sucrose, therefore the drug Alpha Normix® in this dosage form cannot be used in cases of hereditary fructose intolerance, impaired absorption of glucose-galactose, or sucrase-isomaltase deficiency.

Description

Antibiotic, rifaximin.

Dosage form

Tablets, film-coated, pink, round, biconvex.

Use in children

The use of the drug in children under 12 years of age is contraindicated (efficacy and safety have not been established).

Pharmacodynamics

Rifaximin is a broad-spectrum antibiotic from the rifamycin group. Like other representatives of this group, it irreversibly binds the beta subunits of the bacterial enzyme DNA-dependent RNA polymerase and, therefore, inhibits the synthesis of RNA and bacterial proteins.

As a result of irreversible binding to the enzyme, rifaximin exhibits bactericidal properties against sensitive bacteria. The drug has a wide spectrum of antimicrobial activity, including most gram-negative and gram-positive, aerobic and anaerobic bacteria.

The broad antibacterial spectrum of rifaximin helps reduce the pathogenic intestinal bacterial load, which causes some pathological conditions.

The drug reduces:

• the formation by bacteria of ammonia and other toxic compounds, which in the case of severe liver disease, accompanied by a violation of the detoxification process, play a role in the pathogenesis and clinical manifestations of hepatic encephalopathy;
• increased proliferation of bacteria in intestinal microbial overgrowth syndrome;
• the presence of bacteria in the colon diverticulum that may be involved in inflammation in and around the diverticular sac and may play a key role in the development of symptoms and complications of diverticular disease;
• the intensity of the antigenic stimulus, which, in the presence of genetically determined defects in mucosal immunoregulation and/or protective function, can initiate or constantly maintain chronic intestinal inflammation;
• risk of infectious complications during colorectal surgery.

Mechanism of resistance

The development of resistance to rifaximin is caused by reversible damage to the rpoB gene, which encodes bacterial RNA polymerase. The occurrence of resistant subpopulations among bacteria isolated from patients with traveler's diarrhea was low.

According to clinical studies, a three-day course of rifaximin therapy in patients with traveler's diarrhea was not accompanied by the emergence of resistant gram-positive (enterococci) and gram-negative (Escherichia coli) bacteria. With repeated use of rifaximin in high doses in healthy volunteers and in patients with inflammatory bowel diseases, rifaximin-resistant strains appeared, however, they did not colonize the gastrointestinal tract and did not displace rifaximin-sensitive strains.

When therapy was stopped, resistant strains quickly disappeared. Experimental and clinical data suggest that the use of rifaximin in patients with traveler's diarrhea and latent infection with Mycobacterium tuberculosis and Neisseria meningitidis will not be associated with the selection of rifampicin-resistant strains.

Sensitivity

In vitro susceptibility testing cannot be used to determine the sensitivity or resistance of bacteria to rifaximin. At present, clinical data are insufficient to establish cutoff values ​​for evaluating susceptibility tests. Rifaximin was evaluated in vitro against the pathogens of traveler's diarrhea from four regions of the world: enterotoxigenic and enteroaggregative strains of Escherichia coli, Salmonella spp., Shigella spp., non-cholera Vibrio, Plesiomonas spp., Aeromonas spp., and Campylobacter spp. The MIC90 for the isolated strains was 32 μg/ml, a level easily achievable in the intestinal lumen as a result of the high concentration of rifaximin in feces. Because rifaximin alpha polymorph has low absorption from the gastrointestinal tract and acts locally in the intestinal lumen, it may not be clinically effective against invasive bacteria, even if these bacteria are sensitive to it in vitro.

Side effects

Side effects are classified by frequency as follows: very often (≥1/10), often (≥1/100-<1/10), infrequently (≥1/1000-<1/100), rarely (≥1/10 000-<1/1000), very rare (<1/10,000), unknown (frequency cannot be determined based on available data).

From the cardiovascular system: infrequently - a feeling of palpitations, a rush of blood to the skin of the face, increased blood pressure.

From the hematopoietic system: infrequently - lymphocytosis, monocytosis, neutropenia; unknown - thrombocytopenia.

From the immune system: unknown - anaphylactic reactions, hypersensitivity, anaphylactic shock, laryngeal edema.

Metabolic disorders: uncommon - loss of appetite, dehydration.

From the mental side: infrequently - pathological dreams, depressive mood, insomnia, nervousness.

From the side of the central nervous system: often - dizziness, headache; uncommon - hypoesthesia, migraine, paresthesia, drowsiness, pain in the sinuses; unknown - presyncope, agitation.

From the side of the organ of vision: infrequently - diplopia.

From the inner ear: infrequently - ear pain, systemic dizziness.

From the respiratory system: uncommon - shortness of breath, dry throat, nasal congestion, pain in the oropharynx, cough, rhinorrhea.

From the digestive system: often - bloating, abdominal pain, constipation, diarrhea, flatulence, nausea, tenesmus, vomiting, urge to defecate; infrequently - pain in the upper abdomen, ascites, dyspepsia, impaired gastrointestinal motility, mucus and blood in the stool, dry lips, “hard” stools, increased AST activity, ageusia; unknown - changes in liver function tests, heartburn.

From the urinary system: infrequently - glucosuria, polyuria, pollakiuria, hematuria, proteinuria.

From the skin and subcutaneous fat: infrequently - rash, sunburn; unknown - angioedema, allergic dermatitis, exfoliative dermatitis, eczema, erythema, itching, purpura, urticaria, erythematous rash, erythema of the palms, genital itching.

From the musculoskeletal system: uncommon - back pain, muscle spasm, muscle weakness, myalgia, neck pain.

Infections: uncommon - candidiasis, herpes simplex, nasopharyngitis, pharyngitis, upper respiratory tract infections; unknown - clostridial infection.

From the reproductive system: infrequently - polymenorrhea.

Other: often - fever; uncommon - asthenia, pain and discomfort of uncertain localization, chills, cold sweat, flu-like symptoms, peripheral edema, hyperhidrosis, facial swelling, fatigue.

From the laboratory parameters: change in INR.

Use during pregnancy and breastfeeding

Data on the use of Alpha Normix® during pregnancy are very limited. Animal studies have shown a transient effect of rifaximin on ossification and skeletal structure in the fetus. The clinical significance of these results is unknown.

The use of Alpha Normix® during pregnancy is not recommended.

It is not known whether rifaximin passes into breast milk. A risk to a breastfed baby cannot be excluded. To decide whether to continue taking rifaximin during breastfeeding, it is necessary to assess the balance of risk for the child and benefit for the mother.

Interaction

In vitro studies show that rifaximin does not inhibit the isoenzymes of the cytochrome P450 system (CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4) and does not induce CYP1A2 and CYP2B6, but is a weak inducer of CYP3A4. Clinical drug interaction studies indicate that in healthy volunteers, rifaximin does not have a significant effect on the pharmacokinetics of drugs metabolized by CYP3A4. In patients with impaired liver function, it cannot be excluded that rifaximin may reduce the exposure of drugs that are CYP3A4 substrates (for example, warfarin, antiarrhythmics, anticonvulsants) when used simultaneously with them, because in liver failure has a higher systemic exposure compared to healthy volunteers.

In patients continuing to take warfarin and rifaximin, decreases and increases in INR (in some cases with bleeding episodes) were recorded. If coadministration of drugs is necessary, close monitoring of the INR should be performed at the beginning and at the end of treatment. To maintain the desired level of anticoagulation, it may be necessary to adjust the dose of oral anticoagulants.

In vitro studies suggest that rifaximin is a moderate P-glycoprotein substrate and is metabolized by CYP3A4.

It is not known whether the systemic exposure of rifaximin is increased by medicinal products that inhibit CYP3A4 when administered concomitantly.

In healthy volunteers, coadministration of a single dose of cyclosporine (600 mg), a potent P-glycoprotein inhibitor, and a single dose of rifaximin (550 mg) resulted in 83-fold and 124-fold increases in mean rifaximin Cmax and AUC∞. The clinical significance of this increase for systemic exposure is unknown.

Potential interactions of rifaximin with other drugs that are cleared from cells via P-glycoprotein or other transport proteins (MRP2, MRP4, BCRP, BSEP) are unlikely.

Overdose

According to clinical studies in patients with traveler's diarrhea, doses of rifaximin up to 1800 mg/day were well tolerated. Even in patients with normal intestinal bacterial flora, rifaximin at doses up to 2400 mg/day for 7 days did not cause adverse symptoms.

In case of accidental overdose, symptomatic and supportive therapy is indicated.

Impact on the ability to drive vehicles and operate machinery

Although dizziness and drowsiness are observed when using the drug Alpha Normix®, however, it does not have a significant effect on the ability to drive vehicles and engage in activities that require increased attention and speed of psychomotor reactions. If dizziness and drowsiness occur when using the drug, you should refrain from performing these activities.

Side effects of the drug Alpha Normix

Analysis of safety data showed that the risk of side effects when using Alpha Normix is ​​very low. These effects are limited primarily to gastrointestinal disturbances (nausea, dyspepsia, vomiting, abdominal pain and cramps), are mild to moderate and usually self-limit without the need for dose changes or interruption of therapy. The drug is practically not absorbed from the gastrointestinal tract, which eliminates the risk of developing systemic side effects. In rare cases, skin reactions such as urticaria may occur, which are likely due to individual intolerance to treatment. The risk of side effects is 0.7–2% of all cases of drug use. Post-marketing surveillance data confirm the above risk assessment and the nature of the observed events.

Faximin

ConsiliumMedicum. Gastroenterology. (App.) 2009; 01:61-66

In recent years, the indications for the use of antibacterial drugs in gastroenterology have expanded significantly. This happened due to evidence of the role of bacterial flora in the pathogenesis of a number of organic and functional diseases of the gastrointestinal tract (GIT). The use of antibiotics in gastroenterological practice can be divided into three areas:

1 gastrointestinal infection (bacterial diarrhea, cholangitis

2 gastrointestinal diseases that can occur with the addition of an infection, but are not classical infectious diseases (inflammatory bowel diseases, bacterial overgrowth syndrome, Helicobacter pylori -associated diseases);

3 antibiotic prophylaxis before manipulations on the gastrointestinal tract [20].

The anatomical features of the gastrointestinal tract infection determine the choice of antimicrobial drug and the route of its administration. Compared to systemic (absorbable) drugs, local (non-absorbable) antibiotics have a number of advantages: the effect of direct action on the site of infection, a low frequency of systemic side effects, the absence of drug interactions, and a low risk of developing resistant strains [11, 14]. In 2008 In Russia, a new non-absorbing (intestinal) antibacterial drug Alpha Normix (rifaximin) appeared. Alpha Normix (rifaximin) – (4-deoxy-4\'-methylpyrido-[1\', 2\',-1,2] imidazo[5, 4-C]rifamycinSV) is a semisynthetic antibiotic belonging to the rifampicin group. The drug was obtained as a result of experimental synthesis in 1982 (Bologna, Italy) with the aim of creating a non-absorbable antibiotic while maintaining high antibacterial activity. Rifaximin appeared on the Italian pharmaceutical market in 1987. Rifaximin is practically not absorbed from the gastrointestinal tract. The absorption capacity of the drug after oral administration is less than 0.4%. A study conducted on healthy volunteers showed that after oral administration of 400 mg of rifaximin, its concentration in the blood after 1, 2, 4, 8, 12, 24 and 48 hours was below the threshold, i.e. that which could be determined using modern analytical methods (less than 2.5 ng/ml). The total amount of the drug excreted in the urine is 0.007–0.009% of the dose taken [9]. Because inflammatory bowel disease is one of the indications for rifaximin and there is an increased risk of absorption from damaged intestinal mucosa, the absorption of this drug has been carefully studied in patients with mild to moderate ulcerative colitis to determine the risk of systemic side effects. After taking 400 mg of rifaximin, its concentration in the blood was below the limit of detection [22]. This once again confirmed the fact that rifaximin is not absorbed from the gastrointestinal tract. Due to the low bioavailability of the drug and the absence of genotoxic effects in both in vitro and in vivo studies, rifaximin was approved by FDA for use in pregnant women with non-generalized infection. Rifaximin is almost completely excreted unchanged in the feces. After a 3-day administration of rifaximin at a dose of 800 mg/day for traveler's diarrhea, drug concentrations in feces were high (4000–8000 mg/g) and exceeded the minimum inhibitory concentrations for bacteria established in the study [17]. Microbiological studies have established that rifaximin has a bactericidal effect by inhibiting bacterial RNA synthesis as a result of binding of the 3rd unit of bacterial DNA-dependent RNA polymerase [14, 28]. The spectrum of antibacterial activity of the drug is quite broad and includes:

• gram-positive aerobic bacteria: Streptococcus spp., Enterococcus spp. (including Enterococcus fecalis), Staphylococcus spp.;

• gram-negative aerobic bacteria: enteropathogenic strains of Escherichiacoli, Shigellaspp., Salmonellaspp., Yersiniaspp., Proteusspp., Helicobacterpylori;

• gram-positive anaerobic bacteria: Clostridium spp. (including Clostridium difficile and Clostridium perfringens), Peptostreptococcus spp.;

• gram-negative anaerobic bacteria Bacteroidesspp. (including Bacteroidesfragilis), Fusobacterium nucleatum.

MIC50 and MIC90 (minimum inhibitory concentrations capable of stopping the growth of 90% or 50% of strains in vitro) of rifaximin are 1.25 and 50 mg/ml, respectively, against enteropathogenic strains of E. coli, Salmonella and Shigella. While the MIC for Salmonella and enterotoxigenic Escherichia coli ranges from 0.098 to 200 and from 1.25 to 200 mg/ml for Shigella. It is important to note that the resistance of pathogenic bacteria to the drug develops slowly and ranges from 30–90% after a short (5-day) course and after completion of therapy, a rapid disappearance of resistance is observed (after 1–2 weeks), which allows for repeated courses of rifaximin, without fear of developing loss of sensitivity to it [17]. Rifaximin does not affect the secretion of hydrochloric acid, the motor function of the stomach and intestines, as well as the parameters of the cardiovascular and respiratory systems; does not affect the metabolism of other drugs used simultaneously with it, due to the lack of specific effects on cytochrome P-450 enzymes [27]. An analysis of the results of using rifaximin in 8.5 million people showed that the drug has a high safety profile. Side effects (mainly dyspeptic disorders and skin reactions) are rare [9].

To date, more than 2,000 patients have received rifaximin in more than 70 clinical studies.

Infectious diarrhea. Infectious diarrhea can be caused by bacteria, viruses, and protozoa. At least 60% of cases of common infectious diarrhea and 80% of cases of travelers' diarrhea are caused by enteropathogenic bacteria: enterotoxigenic Ecoli, Campylobacter jejuni, Salmonella, Shigella. Treatment of acute infectious diarrhea usually includes rehydration measures, administration of intestinal motility inhibitors, bismuth salts, adsorbents, prebiotics, probiotics. Probiotics are effective in treating rotavirus diarrhea in children. The positive effect of probiotics on the course of acute infectious diarrhea in adults (especially in the first 24–48 hours) has not been proven . According to modern concepts, indications for the use of antibiotics in patients with acute infectious diarrhea are: the invasive nature of intestinal damage with the presence of hemocolitis; severe course of the disease with fever, severe dehydration, especially in young children, elderly patients, patients with immunosuppression; the presence of metastatic microbial damage to internal organs. The most frequently used antibiotics were trimethoprim/sulfamethoxazole, doxycycline, fluoroquinolones, and macrolides [14]. The use of trimethoprim/sulfamethoxazole for acute infectious diarrhea was initially highly effective. However, as the drug was used, the incidence of development of resistant strains began to increase, and it is now rarely used. In the USA, the use of this drug is considered undesirable due to the development of resistant strains. Doxycycline is also not currently the first choice drug for the treatment of acute infectious diarrhea. This is due to the formation of resistant strains and the possibility of developing undesirable side effects (candidiasis, skin reactions). Fluoroquinolones have long been considered the first choice drugs, but they are not recommended for use in children . Recently, the formation of resistance of the bacterial flora to this group of drugs has been increasingly noted; the development of various side effects (arthropathy, skin rash, photosensitivity phenomena) is often associated with their use. Macrolides have been used as an alternative to fluoroquinolones, but the effectiveness of treatment with them is somewhat lower, and the development of side effects (liver damage, hearing impairment) is also possible. The development of rifaximin, a non-absorbable antibacterial drug with a broad spectrum of antibacterial action, has opened up the prospect of a new approach to the safe treatment of acute infectious diarrhea and traveler's diarrhea.

To date, 21 studies have been published that have assessed the use of different doses of rifaximin and compared the drug's effectiveness with other antibacterial agents used to treat infectious and traveler's diarrhea. In a double-blind, randomized trial, 72 adult patients with acute diarrhea were treated with either oral rifaximin (200, 400, 600 mg/day) or trimethoprim/sulfamethoxazole (160/800 mg/day) for 5 days. The duration of diarrhea (time from the start of treatment to the passage of the last unformed stool) was shorter in patients taking rifaximin than in patients receiving trimethoprim/sulfamethoxazole, being 68.1 and 81.9 hours, respectively. The proportion of patients responding to treatment (reduction of diarrhea by 48 hours) was higher when taking rifaximin: at a dose of 200 mg - 83%; 400 mg – 78%; 600 mg – 89% than when taking trimethoprim/sulfamethoxazole (76%) [12]. The effectiveness of rifaximin in treating traveler's diarrhea was compared with that of ciprofloxacin . The time until the last unformed stool was detected during treatment was comparable in both groups. The median was 27.3 and 26 hours in the rifaximin and ciprofloxacin groups, respectively. The researchers concluded that rifaximin is a good alternative to fluoroquinolones in the treatment of acute infectious diarrhea [13]. Prescribing antibacterial therapy in patients with infectious diarrhea helps reduce the severity of clinical symptoms and duration of the disease, reduces the frequency of complications and prevents the spread of infection. If it is necessary to prescribe antibacterial drugs for the treatment of infectious diarrhea, the use of non-absorbable (intestinal) antibacterial drugs (rifaximin) should be considered preferable. In 2004, rifaximin was registered by the US FDA for the treatment of traveler's diarrhea . Prophylactic antimicrobial therapy with rifaximin is recommended to prevent infectious diarrhea in immunocompromised patients or with underlying medical conditions that increase the risk of infection in adverse situations . Recommended doses of rifaximin for the treatment of infectious diarrhea and traveler's diarrhea: 2 tablets (2 times 200 mg) 2 times a day (800 mg/day) for 3 days.

Bacterial overgrowth syndrome (SIBO)

SIBO refers to increased concentrations of bacterial populations (>105 colony-forming units) in small intestinal aspirate and/or the presence of colonic bacteria . The main reason for the development of bacterial overgrowth in the small intestine is a violation of the motor function of the intestine with the formation of stasis of the contents.

The most important etiological factors include:

• dysfunction of the ileocecal valve (inflammatory, tumor processes, primary functional failure);

• consequences of surgical operations (anatomical or formed blind loop, small bowel anastomosis or fistula, vagotomy, cholecystectomy, small bowel resection);

• gastrointestinal diseases associated with motor disorders: gastrostasis, duodenostasis, stasis of contents in the small and large intestines (chronic constipation, including in patients with diabetes);

• disorders of cavity digestion and absorption (maldigestion and malabsorption) caused by achlorhydria of various origins (operated stomach, chronic atrophic gastritis, long-term use of proton pump inhibitors); exocrine pancreatic insufficiency (chronic pancreatitis); pathology of the biliary tract (cholelithiasis, chronic cholecystitis; enteropathy (disaccharidase deficiency and other food intolerances);

• long-term nutritional imbalance;

• chronic inflammatory bowel diseases, diverticulitis, short bowel syndrome;

• entry of bacteria from the extraintestinal reservoir (for example, with cholangitis);

• local and systemic immune disorders: radiation, chemical exposure (cytostatics), AIDS [4].

The frequency of detection of bacterial overgrowth in the small intestine in various gastrointestinal diseases ranges from 70 to 97% []3. The development of SIBO makes a certain contribution to the formation of clinical symptoms of predisposing diseases. The most common manifestations of SIBO are diarrhea, steatorrhea, impaired absorption of vitamin B12, and weight loss.

Treatment guidelines for patients with SIBO include:

1) treatment of the underlying disease (etiological treatment);

2) restoration of the normal composition of intestinal bacteria;

3) restoration of digestion and absorption processes.

Since it is in many cases completely impossible to eliminate the causes leading to the development of SIBO, suppression of excessive microflora growth is the basis of treatment for this syndrome . In the normalization of intestinal microflora, probiotics - preparations containing normal intestinal bacteria - traditionally play an important role [1]. However, in most cases, intestinal decontamination with antibiotics is required. Indications for the prescription of antibacterial agents are: a) excessive bacterial growth in the small intestine, b) translocation of intestinal bacteria outside the intestine, c) inflammatory processes in the intestine, d) identification of opportunistic flora in the intestine, e) lack of effect from treatment without decontamination. A positive effect of antibiotic therapy is a simple and highly specific test that confirms the presence of SIBO [5]. The choice of an antibacterial drug for the treatment of SIBO is often made empirically, since it is almost impossible to isolate microorganisms that cause the formation of this syndrome. Satisfactory results in the treatment of SIBO were obtained using a 10-14-day course of tetracycline at a dose of 250 mg 4 times a day [18]. As an alternative to tetracycline in the treatment of SIBO, attempts have been made to use metronidazole, ampicillin, erythromycin, lincomycin and chloramphenicol. However, these courses were short due to the risk of developing severe side effects, and with repeated courses, the development of resistance to the drugs used was noted.

There is evidence of successful use of rifaximin in the treatment of SIBO. To monitor the treatment of SIBO, in addition to assessing clinical symptoms, indicators of the hydrogen breath test are used (the hydrogen breath test is based on the ability of bacteria to ferment sugars with the formation of large amounts of hydrogen; in the presence of SIBO, the concentration of hydrogen ions in the exhaled air increases). The results of comparative studies of the effectiveness of chlortetracycline and rifaximin in patients with SIBO indicate that normalization of hydrogen breath test indicators after treatment was noted in 70% of patients receiving rifaximin, and only in 27% of those taking tetracycline [11]. The prevalence of SIBO among patients with irritable bowel syndrome (IBS) ranges from 30 to 84% [21]. The presence of SIBO helps explain the symptoms of IBS (bloating, abdominal pain, abnormal bowel movements). Normalization of the microbial biocenosis in the intestine leads to positive dynamics of IBS symptoms. A course of 7-day therapy with rifaximin at a dose of 800 mg/day in patients with IBS led to a significant reduction in the severity of abdominal pain, bloating and flatulence . At the same time, a clear correlation was noted between the indicators of the hydrogen breath test and the number of episodes of flatulence [10]. Recommended treatment regimen for SIBO: rifaximin 2 tablets (2 times 200 mg) 2-3 times a day for 7-10 days. After a course of antibacterial therapy, probiotics are prescribed for 2–4 weeks (without decontamination, probiotics are useless).

Inflammatory bowel diseases

The pathogenesis of inflammatory bowel diseases (IBD) remains unclear. Evidence is accumulating that the intestinal microflora plays a central role in the pathogenesis of IBD. The distal ileum and colon are areas with a high concentration of bacterial flora, and the sites of inflammation in IBD are areas for microbial overgrowth. Experimental data obtained from animal models of IBD support the hypothesis that intestinal microflora and bacterial products may be involved in the initiation and/or maintenance of chronic inflammation in the gut.

The importance of antibacterial therapy in the treatment of IBD has been proven in many clinical studies and is now generally accepted. The most commonly used drugs in general practice are metronidazole and ciprofloxacin. In a randomized controlled trial, the effectiveness of metronidazole 250 mg 4 times daily and ciprofloxacin 500 mg twice daily was comparable to the effectiveness of standard corticosteroid therapy in active Crohn's disease (CD) [26].

Rifaximin was successfully used for the first time in the active stage of IBD in 1997 . Subsequent studies confirmed the positive role of rifaximin in both ulcerative colitis and CD . Thus, 28 patients with moderate to severe ulcerative colitis who did not respond to corticosteroid therapy (methylprednisolone 1 mg/kg/day intravenously) for 7–10 days were randomized to receive rifaximin (400 m/day) or placebo. The addition of rifaximin to the therapy led to a significant reduction in the frequency of stools and rectal bleeding compared to the placebo group. Moreover, treatment with rifaximin significantly reduced the endoscopic disease activity index. After completing a course of treatment with rifaximin and corticosteroids for 6 months, the patients remained in a stable condition [15]. The use of rifaximin in addition to mesalazine for 4 weeks in mild to moderate ulcerative colitis helped reduce the clinical activity index by 30% and made it possible to avoid the use of corticosteroids [22].

Positive results were obtained with the use of rifaximin in patients with CD to prevent postoperative relapse. Rifaximin was prescribed at a daily dose of 1.8 g for 3 months, followed by probiotic therapy 6 g/day for 9 months. After 3 months of therapy, patients receiving rifaximin had a lower incidence of endoscopic exacerbations compared to those receiving mesalazine (10 and 40%, respectively). This trend continued until the end of the study (20 and 40%, respectively) [8].

Recommended regimen for taking rifaximin for IBD: 2 tablets of 200 mg 2-3 times (800-1200 mg) per day for 2-4 weeks to 3 months.

Diverticular disease

Diverticular disease of the colon is a common disease whose incidence increases with age. According to autopsy data, in the USA and Great Britain, colon diverticula were found in 1/3–1/2 of all autopsies in patients over 60 years of age [6].

Most patients with colonic diverticula remain asymptomatic throughout their lives. However, in 20% of cases, symptoms of the disease develop: cramping abdominal pain, flatulence, unstable stool with alternating constipation and diarrhea. Symptomatic diverticular disease is divided into diverticula with and without diverticulitis. Diverticulitis, in turn, can contribute to the development of complications (bleeding, obstruction, perforation ). Disruption of the intestinal microflora plays a key role in the occurrence of symptoms and complications of diverticular disease. The formation of abdominal pain, flatulence, flatulence, and stool disturbances in patients with diverticular disease are caused by excessive gas formation as a result of the breakdown of carbohydrates by microbial flora . Microbial flora is the main source of gases in the intestines. Accumulated gases stretch the intestinal wall, which leads to pain and flatulence. The activity of the microflora that populates diverticula contributes to the formation and maintenance of inflammation and can lead to the development of diverticulitis, including complications.

The main goals of treatment for symptomatic diverticular disease are to reduce the severity of symptoms of the disease and prevent complications. Traditionally, a diet high in dietary fiber is used to prevent diverticulosis. The pain is relieved by prescribing myotropic antispasmodics and analgesics. Diarrhea is eliminated with the help of drugs that suppress peristalsis. For diverticulitis without complications, antibacterial therapy is carried out using oral antibiotics that are active against anaerobes and gram-negative bacilli [6].

The use of antibiotics may be appropriate in patients with diverticular disease and without diverticulitis to control symptoms of the disease. Periodic administration of courses of antibacterial therapy helps to suppress the intestinal flora responsible for the production of gases. Due to this, the breakdown of dietary fiber by bacteria is reduced, the average weight of feces increases, improving their transit through the intestine, which ultimately reduces the symptomatic manifestations of the disease and prevents chronic inflammation in the mucous membrane of the colon. According to the results of a multicenter, double-blind, placebo-controlled study, it was found that in patients with colon diverticula who received rifaximin (400 mg/day) for 7 days every month for 1 year in combination with glucoman (a drug containing dietary fiber) 2 g/day days, the absence of symptoms of the disease was observed in 68.9% of cases, while in the placebo group - only in 39.5% of patients. Thus, this study demonstrates the positive therapeutic effect of rifaximin in patients with diverticular disease in preventing symptoms of the disease [25]. Similar results were obtained in a long-term, prospective, open-label study of 968 patients with symptomatic diverticular disease. Patients were randomized into 2 groups. In the group receiving rifaximin 400 mg 2 times and dietary fiber (glucoman) 4 g/day 7 days monthly for 12 months, 56.5% of patients had no symptoms of the disease, and in the group of patients receiving only glucoman, only 29 had no symptoms of the disease .2% of patients [19].

Thus, the administration of periodic courses of rifaximin in patients with diverticular disease can help reduce the symptoms of the disease and prevent the development of complications.

The recommended regimen for the use of rifaximin for diverticular disease: 2 tablets of 200 mg 2 times (800 mg) per day for 7 days of each month.

Prevention of infectious complications after colorectal surgery

Intra-abdominal infections are a pressing problem. They occupy one of the leading positions in the structure of surgical morbidity and mortality. The most common postoperative complications are anastomotic leakage, infection of the surgical wound, intra-abdominal abscesses and systemic infections (for example, urinary and respiratory systems) may also occur. The cause is most often pathogens – E. coli and anaerobes, especially B. fragilis . An effective guide to the prevention of postoperative complications during colorectal surgery includes a combination of preoperative mechanical preparation of the intestine for surgery, antibacterial prophylaxis and appropriate surgical technique. Combined preventive antibiotic therapy - a combination of oral and parenteral antibiotics (most often cephalosporins) - is recognized as the most effective . In intensive care for abdominal surgical patients, the method of decontamination of the gastrointestinal tract using selective antibiotics (selective decontamination) has been actively used in the last 20 years. In the United States, neomycin and erythromycin are the most commonly used. In Europe and Australia, kanamycin and metronidazole or neomycin and metronidazole are preferred [4]. Currently, experience is accumulating in the use of rifaximin as a means of antibacterial prophylaxis in patients undergoing colorectal surgery. Administration of rifaximin before surgery at a dose of 600 and 800 mg/day significantly reduced the number of both aerobic and anaerobic fecal bacteria [16]. In a comparative study of the effectiveness of rifaximin with parenteral administration of gentamicin or oral administration of paramomycin, the same results were obtained in the prevention of infectious complications during colorectal surgery [29]. By assessing the effectiveness of adding rifaximin (400 mg twice daily) to intravenous cefotaxime (3 g daily dose) for 5 days, researchers concluded that the use of a combination of antibiotics is beneficial in preventing bacterial complications after colon surgery [7].

Recommended regimens for the use of rifaximin for the prevention of infectious complications after colorectal surgery: 2 tablets of 200 mg 2 times (800 mg) per day for 2 days before surgery.

Thus, the effectiveness of the use of rifaximin for established indications has now been proven . Indications for the use of rifaximin can be expanded due to ongoing research on its use in other areas of gastroenterology: H elicobacter pylori infections, C lostridium difficile-associated diseases, prevention of enteropathies associated with the use of non-steroidal anti-inflammatory drugs, selective intestinal decontamination in acute pancreatitis, as well as according to indications outside the gastrointestinal tract (skin infections, bacterial vaginosis, periodontal disease).

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7. Bresadola F, Intini S, Anania G et al. Chemoterapeuticprophilaxis in the preparation of the large intestine for surgical interventions: rifaximin PO vs cephalosporini IV Ann ItalChir 1992; 63:201–7.

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Special instructions for the use of Alpha Normix

During prolonged treatment with high doses or when the intestinal mucosa is damaged, a small amount of the drug (≤1%) may be absorbed, which can cause urine to turn reddish. This is due to the active substance, which, like most antibiotics of this series (rifamycins), has a red-orange color. Use during pregnancy and lactation. Rifaximin did not cause teratogenic effects in rats and rabbits. Adequate data and well-controlled studies in pregnant women are lacking. Since reproductive toxicity studies in animals do not allow assessment of the possibility of a toxic effect in humans, during pregnancy the drug should be taken only in cases of urgent need and under the direct supervision of a physician. The penetration of rifaximin into breast milk has not been studied, but is expected to be negligible due to very low absorption into the systemic circulation. Therefore, the use of Alpha Normix by women who are breastfeeding is permitted with appropriate medical supervision. The ability to influence the reaction rate when driving vehicles or other mechanisms. Not installed.