Description
Latin name
ALFA NORMIX
Release form
Film-coated tablets, pink, round, biconvex.
Packing
14 pcs. – blisters (2) – packs of cardboard.
Pharmacological action
Rifaximin is a broad-spectrum antibiotic from the rifamycin group. Like other representatives of this group, it irreversibly binds the beta subunit of the bacterial enzyme to 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 susceptible bacteria. The drug has a wide spectrum of antimicrobial activity, including most gram-negative and gram-positive, aerobic and anaerobic bacteria.
A wide antibacterial spectrum of rifaximin helps to 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 impaired detoxification, play a role in the pathogenesis and clinical manifestations of hepatic encephalopathy
– increased proliferation of bacteria in the presence of excess
microorganism growth syndrome in the intestine
– intestines of bacteria that can cause inflammation in and around the diverticular sac and possibly play a key role in the development of symptoms and of diverticular disease
– an antigenic stimulus, which in the presence of genetically determined defects in the immune regulation of the mucosa and / or in the protective function, can initiate or constantly maintain chronic intestinal inflammation
– the risk of infectious complications in colorectal surgery.
Resistance Mechanism
The development of rifaximin resistance is due to reversible damage to the rpoB gene, which 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 appearance of resistant gram-positive (enterococci) and gram-negative (E. coli) bacteria. When re-using rifaximin in high doses in healthy volunteers and in patients with inflammatory bowel disease, rifaximin-resistant strains appeared, however, they did not colonize the gastrointestinal tract (GIT) and did not displace rifaximin-sensitive strains.
When therapy was discontinued, resistant strains quickly disappeared. Experimental and clinical data suggest that the use of rifaximin in patients with traveler’s diarrhea and latent infection of Mycobacterium tuberculosis and Neisseria meningitidis will not be accompanied by the selection of rifampicin-resistant strains.
Sensitivity
In vitro susceptibility testing cannot be used to determine the sensitivity or resistance of bacteria to rifaximin. There are not enough clinical data at the moment, to set limits for evaluating sensitivity tests. Rifaximin was evaluated in vitro against pathogens of traveler’s diarrhea from four regions of the world: enterotoxigenic and enteroaggregate strains of E. coli, Salmonella spp., Shigella spp., Non-cholera vibrios, Plesiomonas spp., Aeromonas spp. and Campylobacter spp. MPC90 (minimum inhibitory concentration) for the isolated strains was 32 μg / ml, and this level is easily achieved in the intestinal lumen as a result of the high concentration of rifaximin in feces. Since rifaximin in polymorphic alpha has low absorption from the digestive tract and acts locally in the intestinal lumen, it may be clinically ineffective against invasive bacteria, even if these bacteria are sensitive to it in vitro.
Pharmacokinetics
Absorption
Rifaximin in polymorphic form alpha is practically not absorbed when taken orally (less than 1%). With repeated use in healthy volunteers and in patients with damaged intestinal mucosa, with inflammatory bowel diseases, the plasma concentration is very low (less than 10 ng / ml). When using the drug 30 minutes after ingestion of fatty foods, an increase in the systemic absorption of rifaximin, not having clinical significance, was noted.
Distribution of
Rifaximin binds moderately to plasma proteins. Communication with proteins in healthy volunteers is 67.5%, and in patients with liver failure 62%.
Excretion
Excreted unchanged by the intestines (96.9% of the dose), since it does not undergo degradation and metabolism when passing through the digestive tract. Detected by labeled isotopes in urine, rifaximin is not more than 0.025% of the oral dose. Less than 0.01% of the dose is excreted by the kidneys as 25-deacetylrifaximin, the only metabolite of rifaximin identified in humans. Kidney excretion of 14C rifaximin does not exceed 0.4%. The systemic exposure is non-linear, dose-dependent, which is comparable to the absorption of rifaximin, possibly with a limited dissolution rate.
Special patient groups
With renal failure
There are no clinical data on the use of rifaximin in renal failure.
With liver failure
Systemic exposure in patients with liver failure is greater than that in healthy volunteers. An increase in systemic exposure in these patients should be considered in light of the local effect 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.
Children
The pharmacokinetics of rifaximin in children has not been studied.
Indications
Treatment of gastrointestinal infections caused by bacteria susceptible to rifaximin, for example, acute gastrointestinal infections, traveler ² ¢s diarrhea, intestinal overgrowth syndrome, hepatic encephalopathy, symptomatic inflammatory bowel disease and
Prevention of infectious complications in colorectal surgery.
Contraindications
– Hypersensitivity to rifaximin or other rifamycins or to any of the components that make up the drug.
– Diarrhea accompanied by fever and loose stools with blood.
– Intestinal obstruction (including partial).
– Severe intestinal ulceration.
– Children under 12 years of age (efficacy and safety not established).
– Hereditary fructose intolerance, malabsorption of glucose-galactose, insufficiency of sucrose-isomaltase (for the dosage form granules for the preparation of a suspension for oral administration).
Precautions
Renal failure, concomitant use with oral contraceptives, concomitant use with a P-glycoprotein inhibitor such as cyclosporine.
Use during pregnancy and lactation
Data on the use of Alfa Normix ® during pregnancy is very limited. Animal studies have shown the 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. The risk to the child cannot be ruled out breastfed. To resolve the issue of continued use of rifaximin during breastfeeding, it is necessary to assess the ratio of risk to the baby and the benefits to the mother.
Composition
Each film-coated tablet contains:
Active ingredient:
rifaximin with a polymorphic structure of 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. Film sheath: hypromellose 5.15 mg, titanium dioxide (E171) 1.5 mg, disodium edetate 0.02 mg, propylene glycol 0.5 mg, red oxide red (E172) 0.15 mg.
Dosage and administration
Take orally with a glass of water, regardless of the meal.
Treatment of diarrhea
Adults and children over 12 years of age: 1 tablet of 200 mg or 10 ml of suspension (equivalent to 200 mg of rifaximin) every 6 hours. Treatment of traveler’s diarrhea should not exceed 3 days.
Hepatic encephalopathy:
Adults and children 12 years of age and older: 2 tablets of 200 mg or 20 ml of
suspension (equivalent to 400 mg of rifaximin) every 8 hours. Prevention of postoperative complications in colorectal surgery:
Adults and children over 12 years of age: 2 tablets of 200 mg or 20 ml of suspension (equivalent to 400 mg of rifaximin) every 12 hours.
Prevention is carried out 3 days before surgery.
Overgrowth syndrome:
Adults and children over 12 years of age: 2 tablets of 200 mg every 8-12 hours.
Symptomatic uncomplicated diverticulosis:
Adults and children over 12 years of age: 1-2 tablets of 200 mg or 10 to 20 ml of suspension (equivalent to 200 to 400 mg of rifaximin) every 8-12 hours.
Chronic inflammatory bowel disease:
Adults and children 12 years of age and older: 1-2 tablets of 200 mg or 10 to 20 ml of suspension (equivalent to 200 to 400 mg of rifaximin) 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 20 to 40 days later. 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 their administration can be changed.
Dose adjustment in elderly patients and in patients with hepatic and renal failure is not required.
Preparation of suspension
Granules for preparation of suspension for oral administration are in a hermetically sealed vial. To prepare the suspension,
needs to open the bottle, add water to the mark and shake the bottle well. Add water repeatedly until the suspension reaches the indicated level of 60 ml.
The concentration of rifaximin in the prepared suspension is 100 mg in 5 ml. Shake the suspension well before use. Measure the finished suspension with the measuring cup available in the package.
Side effects
Side effects are classified by frequency of occurrence as follows: very often ( 1/10), often ( 1/100 – 1/10), infrequently ( 1/1000 – 1/100), rarely ( 1/10000 – 1/1000), very rarely ( 1/10000), unknown (frequency cannot be set based on available data).
From the cardiovascular system:
Infrequently: palpitations, flushing of the face, increased blood pressure.
Blood side:
Infrequently: lymphocytosis, monocytosis, neutropenia.
Unknown: thrombocytopenia.
On the part of the immune system:
Unknown: anaphylactic reactions, hypersensitivity, anaphylactic shock, laryngeal edema.
Metabolic disorders:
Infrequently: loss of appetite, dehydration.
Mental disorders:
Infrequently: pathological dreams, depressed mood, insomnia, nervousness.
From the central nervous system:
Often: dizziness, headache.
Infrequently: hypesthesia, migraine, paresthesia, drowsiness, headache in the sinus area.
Unknown: fainting state, arousal.
On the part of the organ of vision:
Infrequently: diplopia.
From the inner ear:
Infrequently: earache, systemic dizziness.
Respiratory:
Infrequently: shortness of breath, dry throat, nasal congestion, pain in the oropharynx, cough, rhinorrhea.
From the gastrointestinal tract and liver:
Often: bloating, abdominal pain, constipation, diarrhea, flatulence, nausea, tenesmus, vomiting, urge to defecate.
Infrequently: pain in the upper abdomen, ascites, dyspepsia, impaired motility of the gastrointestinal tract, secretion of mucus and blood with stools, dry lips, hard stools, increased activity of aspartate aminotransferase, ageusia.
Unknown: impaired 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, pruritus, purpura, urticaria, erythematous rash, erythema of the palms, genital itching.
From the musculoskeletal system:
Infrequently: back pain, muscle spasm, muscle weakness, myalgia, neck pain.
Infections:
Infrequently: candidiasis, herpes simplex, nasopharyngitis, pharyngitis, upper respiratory tract
infection.
Unknown: clostridial infection.
Reproductive system disorders:
Infrequently: polymenorrhea.
Common symptoms:
Often: fever.
Infrequently: asthenia, pain and unpleasant sensations of uncertain localization, chills, cold sweat, flu-like symptoms, peripheral edema, hyperhidrosis, facial edema, fatigue.
Laboratory Research: Changing the International Normalized Relationship.
overdose
According to clinical studies, patients with diarrhea traveler 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 did not cause any adverse symptoms for 7 days. With an accidental overdose, symptomatic and supportive therapy is shown.
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 30 ° C. Shelf life is 3 years.
The shelf life of the prepared suspension is 7 days at room temperature not higher than 30 ° C.
Deystvuyushtee substance
Rifaximin
Dosage form
tablets
Prescription
Prescription
For adults prescribed by a doctor, Nursing mothers as prescribed by a doctor, Children over 12 years old, Children prescribed by a doctor
