Flagyl - instructions for use, doses, side effects, contraindications

Tablets, coated with a shell, round in shape, from white to light yellow color, with engraving "F 250 "on one side. on a cross-section: from white to light yellow color.

Pharmacotherapeutic group:antimicrobial and antiprotozoal agent

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Metronidazole is a derivative of 5-nitroimidazole. The mechanism, actions of metronidazole is the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The restored 5-nitro group of metronidazole interacts with the DNA of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of microorganisms.

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (at t.ch. V. fragilis, B. ovatus, B. distasonis, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp., and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). The MIC for these strains is 0.125-6.25 μg / ml. In combination with amoxicillin shows activity against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

To Metronidazole insensitive Aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional aerobes.

Pharmacokinetics:

Ingestion metronidazole quickly and almost completely absorbed (about 80% per hour). The intake of food does not affect the absorption of metronidazole. Bioavailability of at least 80%. After oral administration of 500 mg of metronidazole, the plasma concentration after 1 hour is 10 μg / ml, and after 3 hours - 13.5 μg / ml. The half-life is 8-10 hours, the connection with blood proteins is insignificant and does not exceed 10-20%. Metronidazole quickly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secret), into breast milk and passes through the placental barrier.

Metabolized about 30-60% of metronidazole by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

Metronidazole is excreted by 40-70% through the kidneys (unchanged - about 35% of the dose).In patients with impaired renal function with a course of metronidazole, an increase in serum concentration is possible.

Indications:

Protozoal infections: extraintestinal amoebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (including).

Infections caused by Bacteroides spp. (incl. V. fragilis, V. distasonis, V. ovatus, B; thetaiotaomicron, B. vulgatus), infections of bones and joints, central nervous system (CNS) infections, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis.

Infections caused by the species Clostridium spp., Peptococcus niger and Peptostreptococcus spp .: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection).

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori (complex therapy).

Prevention of postoperative complications (especially interference on the colon, paraectal area, appendectomy, gynecological operations).

Contraindications:

- Hypersensitivity to imidazoles, as well as to nitroimidazole derivatives.

- Organic lesions of the central nervous system (including epilepsy).

- Leukopenia (including anamnesis).

- Hepatic insufficiency (in the case of the appointment of large doses).

- Pregnancy.

- Lactation period.

- Children up to 10 years.

Carefully:

- Hepatic encephalopathy.

- Acute and chronic diseases peripheral and central nervous system (risk of weighting in neurological symptoms).

- Renal failure.

Dosing and Administration:

Metronidazole is intended for oral administration, before or after a meal. Drink plenty of water.

With intestinal amebiasis Flagyl® is used for 7 days to 1500 mg per day for three doses. In acute amoebic dysentery, the daily dose is 2,250 mg divided into three doses. Children from 10 to 15 years - 500 mg per day, divided into 2 doses.

With abscess of the liver and other extraintestinal forms of amoebiasis the maximum daily dose is 2500 mg, divided into 3 doses for 3-5 days, in combinations with tetracycline antibiotics and other therapies. Children from 10 to 15 years - 500 mg per day, divided into 2 doses.

With trichomoniasis in women (urethritis and vaginitis) Flagil® is prescribed once in a dose of 2 g or as a course of treatment for 10 days: 1 tab. (250 mg) 2 times a day.

With trichomoniasis in men (urethritis) Flagil® is administered once in a dose of 2 g or as a course treatment for 10 days of 1 tab. (250 mg) 2 times a day.

Treatment of anaerobic infections usually begin with intravenous infusions, with the subsequent transition to tablets. For adults, the dose of Flagil® is 500 mg 3 times a day. The duration of treatment is up to 7 days.

For the treatment of pseudomembranous colitis prescribe 500 mg of Flagil® (2 tablets) 3-4 times a day. The duration of treatment is determined by the doctor.

For eradication Helicobacter pylori prescribe 500 mg of Flagil® 3 times a day as part of a combination therapy (for example, with amoxicillin).

For the prevention of postoperative complications appoint 750-1500 mg per day in 3 divided doses 3-4 days before surgery. 1-2 days after the operation (when ingestion is already permitted) - 750 mg of Flagil® per day for 7 days.

Side effects:

Disorders from the gastrointestinal tract

Pain in epigastrium, nausea, vomiting, diarrhea.

Inflammation of the oral mucosa (glossitis, stomatitis), taste disorders ("metallic" taste in the mouth), decreased appetite, anorexia, dryness of the oral mucosa, constipation.

Pancreatitis (reversible cases).

Changing the color of the tongue / "lined tongue" (due to the growth of the fungal microflora).

Immune system disorders

Angioedema, anaphylactic shock.

Disturbances from the nervous system

Peripheral sensory neuropathy.

Headache, cramps, dizziness.

The development of encephalopathy (for example, confusion) has been reported and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disorders, nystagmus and tremor), which undergo reverse development after metronidazole withdrawal.

Aseptic meningitis.

Disorders of the psyche

Psychotic disorders, including confusion, hallucinations.

Depression, insomnia, irritability, increased excitability.

Disturbances on the part of the organ of sight

Transient visual impairments, such as diplopia, myopia, vagueness of contours subjects, reduction of visual acuity, violation of color perception.

Neuropathy / optic neuritis.

Violations of the blood and lymphatic system

Agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

Disturbances from the liver and bile ducts

Increased activity of "hepatic" enzymes (aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice.

In patients treated with metronidazole in combination with other antibiotics, cases of hepatic insufficiency that required liver transplantation were observed.

Disturbances from the skin and subcutaneous tissues

Rash, itching, flushing of the skin, hives.

Pustular skin rash.

Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract

It is possible to stain urine in a brownish-reddish color, due to the presence in the urine of a water-soluble metabolite of metronidazole.

Dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders at the site of administration

Fever, nasal congestion, arthralgia, weakness.

Laboratory and instrumental data

Compaction of the T wave on the ECG.

Interaction:

FROM disulfiram

It was reported about the development of psychotic reactions in patients receiving concomitantly metronidazole and disulfiram (the interval between the appointment of these metronidazoles should be at least 2 weeks).

FROM ethanol

Possible occurrence of difulfiramoid-like reactions (flushing of the skin, vomiting, tachycardia).

With indirect anticoagulants (warfarin)

Increased anticoagulant effect and increased hemorrhagic risk associated with a slowdown in their hepatic metabolism, which may lead to an increase in prothrombin time. In case of simultaneous application, more frequent monitoring of prothrombin time and, if necessary, correction of anticoagulant doses are required.

With lithium preparations

With the simultaneous administration of metronidazole with lithium preparations, the concentration of the latter in the blood plasma can increase. With simultaneous use, plasma concentrations of lithium, creatinine and electrolytes should be monitored.

With cyclosporine

With the simultaneous administration of metronidazole with cyclosporine, the serum concentration of cyclosporine can increase. If simultaneous use of these two metronidazoles is required, monitoring of the serum concentration of cyclosporine and creatinine is required.

With cimetidine

Cimetidine inhibits metronidazole metabolism, which can lead to an increase in its serum concentration and an increased risk of side effects.

With drugs that induce enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin)

Simultaneous administration of metronidazole with drugs that stimulate enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, as a result of which its concentration in the plasma decreases.

FROM fluorouracil

Metronidazole reduces the clearance of fluorouracil, leading to an increase in its toxicity.

With busulfan

Metronidazole increases the concentration of busulfan in the blood plasma, which can lead to the development of severe toxic effects of busulfan.

With nondepolarizing muscle relaxants (vecuronium bromide)

It is not recommended to combine with nondepolarizing muscle relaxants (vecuronium bromide).

Sulfonamides enhance the antimicrobial effect of metronidazole.

Special instructions:

Because the simultaneous use of metronidazole with alcohol can have an effect similar to the effect of disulfiram (a feeling of heat, vomiting, tachycardia),should warn patients that during treatment with the drug Flagil ® should not use alcoholic beverages or drugs containing alcohol.

It is necessary to carefully weigh the indications for long-term use of the drug and without strict indications to avoid its long-term use. If, in the presence of strict indications, the drug is used for longer than it is usually recommended, then treatment should be controlled by hematological parameters and adverse reactions, such as peripheral or central neuropathy (paresthesia, ataxia, dizziness, convulsions), upon which treatment should be discontinued .

When treating trichomonas vaginitis in women and trichomoniasis in men, it is necessary to abstain from sexual intercourse. It is necessary to simultaneously treat sexual partners.

Treatment does not stop during menstruation. After therapy with trichomoniasis, control tests should be performed for 3 consecutive cycles before and after menstruation.

It is necessary to take into account that metronidazole can immobilize treponemy, which leads to a false positive test of Nelson.

Effect on the ability to drive transp. cf. and fur:

Given the profile of side effects (dizziness, visual impairment and others), it is recommended during treatment to refrain from driving, from practicing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 250 mg.

Packaging:

For 10 tablets in a blister of PVC / aluminum foil.

2 blisters together with instructions for use in a cardboard box.

Storage conditions:

Store in a dark place at a temperature of no higher than 30 FROM.

Keep out of the reach of children.

Shelf life:

3 years.

After the expiration date, the drug can not be used.

Terms of leave from pharmacies:On prescription

Registration number:P N008782

Date of registration:23.03.2011 / 31.07.2013

Expiration Date:Unlimited

The owner of the registration certificate:Sanofi-Aventis FranceSanofi-Aventis France France

Manufacturer: & nbsp

SANOFI-AVENTIS S.A. Spain

Representation: & nbspSanofi Aventis GroupSanofi Aventis Group

Information update date: & nbsp11.09.2016

Illustrated instructions

Instructions

Flagil® (Flagyl®)