Alfa Normix pills 200 mg, 36 pcs.

Composition

Each film-coated tablet contains:

Active ingredient: 

rifaximin with alpha polymorphic structure 200 mg.

Auxiliary substances:sodium carboxymethyl starch 15 mg, glyceryl palmitostearate 18 mg, colloidal silicon dioxide 1 mg, talc 1 mg, microcrystalline cellulose 115 mg. Film shell:hypromellose 5.15 mg, titanium dioxide (E 171) 1.5 mg, disodium edetate 0.02 mg, propylene glycol 0.5 mg, red iron oxide (E 172) 0.15 mg

. Pharmacological action

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

consequently, inhibits the synthesis of bacterial RNA and proteins.

As a result of its 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 to reduce the pathogenic intestinal bacterial load, which causes some pathological conditions.

The drug reduces:

– the formation of bacteria, 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 the proliferation of bacteria with the syndrome of excessive

growth of microorganisms in the intestines;

– the presence of diverticula in the colon bacteria that can cause inflammation within and around the diverticular pouch and may play a key role in the development of symptoms and complications of diverticular disease;

– antigenic stimulus, which in the presence of a genetically determined defects in mucosal immune regulation and/or protective functions may initiate or to constantly maintain a chronic inflammation of the intestine;

the risk of infectious complications in colorectal surgery.

Mechanism of resistance

The development of rifaximin resistance 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 appearance of resistant gram-positive (enterococci) and gram-negative (Escherichia coli) bacteria. When rifaximin was repeated 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 (GIT) and did not displace rifaximin-sensitive strains.

When therapy was discontinued, the 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 accompanied by the selection of rifampicin-resistant strains.

Sensitivity

In vitro sensitivity testing cannot be used to determine the sensitivity or resistance of bacteria to rifaximin. Currently, there is insufficient clinical data to establish limits for evaluating sensitivity tests. Rifaximin was evaluated in vitro against pathogens of traveler’s diarrhea from four regions of the world: enterotoxigenic and enteroaggregative strains of E. coli, Salmonella spp., Shigella spp., non-cholera vibrios, Plesiomonas spp., Aeromonas spp. and Campylobacter spp. MPC 90 (minimum inhibitory concentration) for the isolated strains was 32 micrograms / ml, and this level is easily achievable in the intestinal lumen as a result of the high concentration of rifaximin in faeces. Since rifaximin in the alpha polymorphic form is poorly absorbed from the gastrointestinal 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 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, with inflammatory bowel diseases, the plasma concentration is very low (less than 10 ng / ml). When using the drug 30 minutes after taking a fatty meal, an increase in systemic absorption of rifaximin that does not have clinical significance was noted.

Distribution

Rifaximin is moderately bound to plasma proteins. Protein binding is 67.5% in healthy volunteers and 62% in patients with hepatic insufficiency.

Deduction

It is excreted unchanged by the intestines (96.9% of the dose taken), as it does not undergo degradation and metabolism during passage through the gastrointestinal tract. Detectable by labeled isotopes in the urine, rifaximin is no more than 0.025% of the oral dose. Less than 0.01% of the dose is excreted by the kidneys as 25-deacetylriphaximin, the only rifaximin metabolite identified in humans. Renal excretion of 14C rifaximin does not exceed 0.4%. Systemic exposure is non-linear, dose-dependent, which is comparable to rifaximin absorption, possibly limited by the dissolution rate.

Special patient groups

With kidney failure

There are no clinical data on the use of rifaximin in patients with renal insufficiency.

With liver failure

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

The pharmacokinetics of rifaximin in children have not been studied.

Indications

Treatment of gastrointestinal infections caused by rifaximin-sensitive bacteria, such as acute gastrointestinal infections, traveler’s diarrhea, intestinal overgrowth syndrome, hepatic encephalopathy, symptomatic uncomplicated diverticular colon disease, and chronic intestinal inflammation.

Prevention of infectious complications during 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 ulcerative bowel disease.

– Children under 12 years of age (efficacy and safety have not been established).

– Hereditary fructose intolerance, glucose-galactose malabsorption, sucrose-isomaltase insufficiency (for the dosage form of granules for preparing a suspension for oral administration).

With caution

Renal insufficiency, concomitant use with oral contraceptives, concomitant use with a P-glycoprotein inhibitor such as cyclosporine.

Side effects

Side effects are classified by frequency as follows: very common (≥1/10), common (≥1/100 – 1/10), uncommon (≥1/1000 – 1/100), rare (≥1/10000 – 1/1000), very rare (1/10000), unknown (frequency cannot be determined based on available data).

From the cardiovascular system:

Infrequently: palpitation of the heart, “flushes” of blood to the skin of the face, increased blood pressure.

From the blood side:

Infrequently: lymphocytosis, monocytosis, neutropenia.

Unknown: thrombocytopenia.

From the immune system:

Unknown: anaphylactic reactions, hypersensitivity, anaphylactic shock, laryngeal edema.

Metabolic disorders:

Infrequently: decreased appetite, dehydration.

Mental disorders:

Infrequently: abnormal dreams, depressive mood, insomnia, nervousness.

From the central nervous system:

Often: dizziness, headache.

Infrequently: hypesthesia, migraine, paresthesia, drowsiness, sinus headache.

Unknown: pre-fainting state, agitation.

From the side of the visual organ:

Infrequently: diplopia.

From the inner ear:

Infrequently: ear pain, systemic dizziness.

Respiratory system disorders:

Infrequently: shortness of breath, dry throat, nasal congestion, oropharyngeal pain, 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 gastrointestinal motility, mucus and blood with stool, dry lips, “hard” stool, increased aspartate aminotransferase activity, ageusia.

Unknown: violation of liver function tests, heartburn.

From the urinary system:

Infrequently: glucosuria, polyuria, pollakiuria, hematuria, proteinuria.

Skin and subcutaneous fat disorders:

Infrequently: rash, sunburn.

Unknown: angioedema, allergic dermatitis, exfoliative dermatitis, eczema, erythema, pruritus, purpura, urticaria, erythematous rash, erythema of the palms, pruritus of the genitals.

From the musculoskeletal system:

Infrequently: back pain, muscle spasm, muscle weakness, myalgia, neck pain.

Infections:

Infrequently:candidiasis, herpes simplex, nasopharyngitis, pharyngitis,

upper respiratory tract infections.

Unknown: clostridial infection.

From the side of the reproductive system:

Infrequently: polymenorrhea.

Common symptoms:

Common: fever.

Infrequently: asthenia, pain and discomfort of indeterminate localization, chills, cold sweat, flu-like symptoms, peripheral edema, hyperhidrosis, facial edema, fatigue.

Laboratory studies: changing the international normalized attitude.

Interaction

In vitro studies show that rifaximin does not inhibit cytochrome P-450 isoenzymes (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 rifaximin does not significantly affect the pharmacokinetics of drugs metabolized with CYP3A4 in healthy volunteers. In patients with impaired liver function, it cannot be excluded that rifaximin may reduce the exposure of drugs of CYP3A4 substrates (for example, warfarin, antiarrhythmic, anticonvulsants, etc. ) when used simultaneously with them, since it has a higher systemic exposure in patients with hepatic insufficiency compared to healthy volunteers.

In patients who continue to take warfarin and rifaximin, a decrease and increase in the international normalized ratio (in some cases with episodes of bleeding) were recorded. If co-administration of drugs is necessary, careful monitoring of the international normalized ratio should be carried out 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 substrate of P-glycoprotein and is metabolized by the CYP3A4 isoenzyme.

It is not known whether drugs that inhibit CYP3A4 when co-administered with rifaximin increase the systemic exposure of rifaximin.

In healthy volunteers, co-administration of a single dose of cyclosporine (600 mg), a potent P-glycoprotein inhibitor, and a single dose of rifaximin (550 mg) resulted in an 83-fold and 124-fold increase in the mean Cmax and AUC∞ of rifaximin. The clinical significance of this increase for systemic exposure is not known.

Potential interactions of rifaximin with other drugs that are removed from the cell by P-glycoprotein or other transport proteins (MRP2, MRP4, BCRP, BSEP) are unlikely.

How to take, course of administration and dosage

Take orally with a glass of water, regardless of food intake.

Treatment of diarrhea

Adults and children over 12 years of age: 1 200 mg tablet or 10 ml suspension (equivalent to 200 mg rifaximin) every 6 hours. Treatment of traveler’s diarrhea should not exceed 3 days.

Hepatic encephalopathy:

Adults and children over 12 years of age: 2 tablets of 200 mg or 20 ml

suspension (equivalent to 400 mg 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 suspension (equivalent to 400 mg rifaximin) every 12 hours.

Prevention is carried out 3 days before the operation.

Bacterial 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 diseases:

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.

The duration of treatment with Alfa Normix should not exceed 7 days. A second course of treatment should be carried out no earlier than in 20-40 days. The total duration of treatment is determined by the clinical condition of the patients. On the recommendation of the doctor, the dosage and frequency of their administration can be changed.

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

Preparation of the suspension

Granules for the preparation of a suspension for oral administration are in a hermetically sealed bottle. To prepare the suspension

, open the bottle, add water up to the mark and shake the bottle well. Add water again until the suspension level reaches the specified 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 using the measuring cup provided in the package.

Overdose

According to clinical studies, rifaximin doses up to 1800 mg/day were well tolerated in patients with traveler’s diarrhea.

Even in patients with normal intestinal bacterial flora, rifaximin at a dose of up to 2400 mg / day for 7 days did not cause adverse symptoms. In case of accidental overdose, symptomatic and supportive therapy is indicated.

Special instructions

Clinical data indicate that Alfa Normix® is ineffective in the treatment of intestinal infections caused by Campylobacter jejuni, Salmonella spp., and Shigella spp., which cause frequent diarrhea, fever, and stool discharge. Alfa Normix® is not recommended for use if patients experience fever and loose stools with blood. Alfa Normix should be discontinued if symptoms of diarrhea worsen or persist for more than 48 hours. Another antibacterial therapy should be prescribed. Treatment of 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 Alfa Normix®. A potential association of Alfa Normix with the development of Clostridium difficile-associated diarrhea and pseudomembranous colitis cannot be excluded. There is no experience of using rifaximin together with other rifamycins.

Caution should be exercised when taking rifaximin concomitantly with a P-glycoprotein inhibitor such as cyclosporine.

Patients should be warned that, despite the slight absorption of rifaximin (less than 1%), it can cause a reddish color in the urine: this is due to the Active ingredient rifaximin, which, like most antibiotics of this series (rifamycins), has a reddish – orange color.

If a superinfection develops with microorganisms that are insensitive to rifaximin, Alfa Normix® should be discontinued and appropriate therapy should be prescribed.

 Due to the influence of Alfa Normix® the effect 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 Alfa Normix®, especially if the estrogen content of oral contraceptives is less than 50 mcg.

Alfa Normix® should be taken no earlier than 2 hours after taking activated charcoal.

Granules for the preparation of a suspension for oral administration contain sucrose, so Alfa Normix® in this dosage form can not be used for hereditary fructose intolerance, glucose-galactose malabsorption, sucrose-isomaltase deficiency.

Influence on the ability to drive vehicles and mechanisms

Although dizziness and drowsiness are observed with the use of Alfa Normix®, however, it does not significantly affect the ability to drive vehicles and engage in activities that require increased attention and speed of psychomotor reactions. In case of dizziness and drowsiness when using the drug, you should refrain from performing these activities.

Form of production

coated tablets

Storage conditions

Keep out of reach of children at a temperature not exceeding 30°C.

Active ingredient

Rifaximin

Conditions of release from pharmacies

By prescription

Dosage form

of the tablet

Purpose

For children over 11 years of age, For adults as prescribed by a doctor, For nursing mothers as prescribed by a doctor, For children as prescribed by a doctor, For children over 12 years of age

Indications

Intestinal Infections, Diarrhea, Colitis, Salmonellosis, Poisoning

Weight

Weight: 30 gr.