Alfa Normix, 200 mg 36 pcs.

Pharmacological action Pharmacological action – antibacterial.

Pharmacodynamics

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

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 wide antibacterial spectrum of rifaximin helps to reduce pathogenic intestinal bacterial load that causes some pathological conditions.

The drug reduces:

– production by bacteria of ammonia and other toxic compounds, which in the case of severe liver disease, accompanied by impaired detoxification process, play a role in the pathogenesis and clinical manifestations of hepatic encephalopathy;

– increased bacterial proliferation in gut microbial overgrowth syndrome;

– the presence of bacteria in the colonic diverticulum, which may cause inflammation in and around the diverticular sac and may play a key role in the development of symptoms and complications of diverticular disease;

– an antigenic stimulus that, in the presence of genetically determined defects in mucosal immunoregulation and/or protective function, may initiate or permanently maintain chronic intestinal inflammation;

The risk of developing infectious complications in colorectal surgery.

The mechanism of resistance. The development of resistance to rifaximin is due to reversible damage to the rpoB gene that encodes bacterial RNA polymerase. The incidence 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 occurrence of resistant Gram-positive (enterococci) and Gram-negative (E. coli) bacteria. When rifaximin was repeatedly administered at high doses in healthy volunteers and patients with inflammatory bowel disease, rifaximin-resistant strains appeared, but they did not colonize the GI tract or displace rifaximin-sensitive strains.

The resistant strains quickly disappeared when therapy was discontinued. Experimental and clinical data suggest that the use of rifaximin in patients with traveler’s diarrhea and latent Mycobacterium tuberculosis and Neisseria meningitidis infection will not be accompanied by selection of rifampicin-resistant strains.

Sensitivity. In vitro sensitivity testing cannot be used to determine the sensitivity or resistance of bacteria to rifaximin. There is currently insufficient clinical data to establish limits for evaluating sensitivity tests. Rifaximin was evaluated in vitro against traveler’s diarrhea pathogens from four regions of the world: enterotoxigenic and enteroaggregative strains of E. coli, Salmonella spp., Shigella spp., noncholera vibrios, Plesiomonas spp., Aeromonas spp. and Campylobacter spp. The MPC90 for the isolated strains was 32 μg/mL, and this level was easily attainable in the intestinal lumen as a result of the high concentration of rifaximin in the feces. Because rifaximin in polymorphic alpha has low gastrointestinal absorption and acts locally in the gut lumen, it may not be clinically effective against invasive bacteria even if these bacteria are sensitive to it in vitro.

Pharmacokinetics

Intake. Rifaximin in polymorphic form alpha is practically not absorbed when administered orally (less than 1%). When repeated use in healthy volunteers and patients with damaged intestinal mucosa and inflammatory bowel disease, plasma concentrations are very low (less than 10 ng/ml). When using the drug 30 min after a fatty meal, an increase in systemic absorption of rifaximin of no clinical significance was observed.

Distribution. Rifaximin is moderately bound to plasma proteins. Protein binding in healthy volunteers is 67.5%, in patients with hepatic impairment – 62%.

Elimation. It is excreted unchanged in intestinal form (96.9% of the administered dose), because it is not degraded and metabolized during passage through the gastrointestinal tract.

Rifaximin detected with labeled isotopes in urine is not more than 0.025% of the oral dose. Less than 0.01% of the dose is excreted by the kidneys as 25-desacetylrifaximin, the only rifaximin metabolite identified in humans. Renal excretion of 14C rifaximin does not exceed 0.4%. Systemic exposure is nonlinear, dose-dependent, which is comparable to the absorption of rifaximin, possibly limited by the rate of dissolution.

Particular patient groups

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

With hepatic impairment. Systemic exposure in patients with hepatic impairment is greater than in healthy volunteers. Increased systemic exposure in these patients should be considered in light of the local action of rifaximin in the gut and its low systemic bioavailability, as well as available data on the safety of rifaximin in patients with cirrhosis.

Children. The pharmacokinetics of rifaximin in children have not been studied.

Indications

Active ingredient

Composition

How to take, the dosage

Interaction

Special Instructions

Contraindications

Side effects

Overdose

Pregnancy use