Metronidazole - instructions for use, dose, side effects, contraindications

The mechanism of action is the biochemical reduction of the 5-nitro group by intracellular transport proteins of anaerobic microorganisms and protozoa, the restored 5-nitro group interacts with the deoxyribonucleic acid (DNA) of the microorganism cell, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active with respect to Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., as well as obligate anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (P. bivia, P. buccae, R. disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The minimum inhibitory concentration 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).

Metronidazole is not sensitive to aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) Metronidazole acts synergistic antibiotics, effective against conventional aerobes.

Increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like action), stimulates reparative processes

Pharmacokinetics:

Absorption is high (bioavailability is not less than 80%). It has a high penetrating ability, reaching bactericidal concentrations in most tissues and body fluids, including lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk, penetrates the blood-brain and placental barrier. The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg.

The maximum concentration of the drug in the blood (C_mOh) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration (TC_mOh) - 1-3 hours. Communication with plasma proteins - 10-20%.

In the body, about 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

The half-life (T_1/2) with normal liver function - 8 hours (6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns: those born at the time of pregnancy - 28-30 weeks - about 75 hours, respectively, 32-35 weeks - 35 hours, 36-40 weeks - 25 hours. It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%.

Kidney clearance - 10.2 ml / min. In patients with impaired renal function after repeated administration, cumulation of metronidazole in serum can be observed (therefore, the frequency of admission should be reduced in patients with severe renal insufficiency).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T_1/2 is reduced to 2.6 hours). When peritoneal dialysis is withdrawn in small quantities.

Indications:

Protozoal infections: intestinal amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, giardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomoniasis urethritis.

Infections caused by Bacteroides spp. (including W. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus): infection of bones and joints, infections of the central nervous system (CNS), incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess.

Infections caused by the species Bacteroides, including a group AT. fragilis, species Clostridium, Peptococcus and Peptostreptococcus: infection of the abdominal cavity (peritonitis, liver abscess), infection of the pelvic organs (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, vaginal vaginal infection after surgical operations), skin and soft tissue infections,

Infections caused by the species Bacteroides, including group V. fragilis and species Clostridium: sepsis.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori, alcoholism.

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

Radiation therapy of patients with tumors - as a radiosensitizer, in cases where tumor resistance is caused by hypoxia in tumor cells.

Contraindications:

Hypersensitivity, leukopenia (incl.in anamnesis), organic lesions of the central nervous system (including epilepsy), liver failure (in the case of high doses), pregnancy (I trimester), lactation.

Carefully:Pregnancy (II-III trimesters), renal / hepatic insufficiency.

Pregnancy and lactation:

During lactation it is recommended to stop breastfeeding.

Dosing and Administration:

Inside, during or after a meal, (or squeezed milk), without chewing.

With trichomoniasis - 250 mg twice a day for 10 days or 400 mg twice a day for 5-8 days.

Women it is necessary to additionally appoint metronidazole in the form of vaginal suppositories or tablets. If necessary, you can repeat the course of treatment or increase the dose to 0.75-1 g / day. Between the courses should be a break in 3-4 weeks with the implementation of repeated control laboratory tests. An alternative scheme of therapy is the appointment of 2 g once to the patient and his sexual partner.

Children 2-5 years old - 250 mg / day; 5-10 years - 250-375 mg / day, over 10 years old - 500 mg / day. The daily dose should be divided into 2 divided doses. The course of treatment is 10 days.

With giardiasis - 500 mg twice a day for 5-7 days.

Children up to 1 year old - 125 mg / day, 2-4 years old - 250 mg / day, 5-8 years - at 375 mg / day, over 8 years old - 500 mg / day (in 2 divided doses). The course of treatment is 5 days.

With giardiasis - 15 mg / kg / day in 3 divided doses for 5 days.

Adults: for asymptomatic amoebiasis (if a cyst is detected) a daily dose of 1-1.5 g (500 mg 2-3 times a day) for 5-7 days.

With chronic amebiasis daily dose of 1.5 g in 3 divided doses for 5-10 days, with acute amoebic dysentery - 2.25 g in 3 divided doses until symptoms stop.

With liver abscess the maximum daily dose is 2.5 g in 1 or 2-3 doses, for 3-5 days, in combination with antibiotics (tetracyclines) and other methods of therapy.

Children 1-3 years old -1/4 the dose of an adult, 3-7 years -1/3 of the adult dose, 7-10 years old -1/2 doses of an adult.

With balantidiasis - 750 mg 3 times a day for 5-6 days.

With ulcerative stomatitis adults appoint 500 mg twice a day for 3-5 days; children in this case, the drug is not shown.

With pseudomembranous colitis - 500 mg 3-4 times a day.

For eradication of Helicobacter pylori - 500 mg 3 times a day for 7 days (as part of combination therapy, for example, combination with amoxicillin 2.25 g / day).

In the treatment of anaerobic infection the maximum daily dose is 1.5-2 g.

In the treatment of chronic alcoholism prescribe 500 mg / day for a period of up to 6 (not more) months.

For the prevention of infectious complications - 750-1500 mg / day in 3 divided doses 3-4 days before surgery, or once 1 g in the first day after the operation. In 1-2 days after the operation (when already allowed ingestion) - 750 mg / day for 7 days.

With severe renal dysfunction (CC less than 10 ml / min) daily dose should be reduced by half.

Side effects:

From the digestive system: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, "metallic" taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis.

From the nervous system: dizziness, impaired coordination of movements, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy.

Allergic reactions: urticaria, skin rash, skin hyperemia, nasal congestion, fever, arthralgia.

From the genitourinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color.

Other: neutropenia, leukopenia, flattening of the T wave on the electrocardiogram.

Interaction:

Increases the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Similarly to disulfiram, causes intolerance to ethanol.Simultaneous use with disulfiram can lead to the development of various neurologic symptoms (the interval between appointments is at least 2 weeks).

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

Simultaneous administration of drugs stimulating 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.

With simultaneous administration with lithium preparations, the concentration of the latter in the plasma and the development of symptoms of intoxication may increase.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

Special instructions:

During the period of treatment, ethanol intake is contraindicated (a disulfiram-like reaction may develop: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).

In combination with amoxicillin it is not recommended to use in patients younger than 18 years.

With prolonged therapy, it is necessary to monitor the blood picture.

With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

The appearance of ataxia, dizziness and any other worsening of the neurological status of patients requires discontinuation of treatment.

Can immobilize treponema and lead to Nelson's false positive test.

Stains urine in a dark color.

When treating trichomonadal vaginitis in women and trichomoniasis in men, it is necessary to abstain from sexual activity. It is necessary to simultaneously treat sexual partners. Treatment does not stop during menstruation. After trichomoniasis therapy, control tests should be performed for three consecutive cycles before and after menstruation.

After treatment of giardiasis, if symptoms persist, after 3 to 3 weeks, 3 feces should be analyzed at intervals of several days (in some successfully treated patients lactose intolerance caused by invasion may persist for several weeks or months, recalling the symptoms of giardiasis).

Form release / dosage:

Tablets, 250 mg.

Packaging:

For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50, 60 or 100 tablets in cans of polymeric for medicines.

One jar or 1, 2, 3, 4, 5, 6, 8 or 10 contour squares, together with the instructions for use, are placed in a cardboard package (bundle).

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N003467 / 01

Date of registration:27.04.2009 / 27.02.2013

Expiration Date:Unlimited

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)