Metronidazole solution for infusion 5 mg/ml - - Catalog Production of medicines

pharmachologic effect

Metronidazole is a broad-spectrum antiprotozoal and antibacterial agent.

Active against Trichomonas vaginalis, Entamoeba histolytica, as well as gram-negative anaerobes Bacteroides spp. (including B.fragilis, B.distasonis, B.ovatus, B.thetaiotaomicron, B.vulgatus), Fusobacterium spp. and some gram-positive anaerobes (susceptible strains of Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.).

Aerobic microorganisms and facultative anaerobes are not sensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), metronidazole acts synergistically with antibiotics that are effective against common aerobes.

The use of a combination of metronidazole and miconazole in the correction of vaginal dysbiosis

Introduction

One of the most common complaints when women visit a gynecologist is pathological discharge from the genital tract (leucorrhoea). The cause of pathological vaginal discharge can be a number of diseases and conditions [1]. According to various researchers, in 22–50% of cases, leucorrhoea is a symptom of bacterial vaginosis (BV) [2]. BV is a non-inflammatory disease of the vagina associated with changes in its microflora. This condition is extremely widespread among women of fertile age (20–45 years), its incidence in this group reaches 80%, i.e., out of 10 women, 8 experience BV at least once in their life. The disease does not pose a danger to the patient herself, but can negatively affect her reproductive function. BV often causes miscarriages, intrauterine fetal infections, complications after childbirth, abortions, and invasive interventions on the genitals. It has now become known that the vaginal microbiocenosis is a dynamic and much more complex ecosystem than previously thought. The state of the microflora of the genital area most seriously affects the health of women as a whole [2]. For the first time in 1892, Doderlein presented descriptions and images of the vaginal bacillus, subsequently named after him, and divided the bacterial communities of the female genital tract into “normal” (with a predominance of vaginal lactic acid bacilli) and “abnormal” (containing other numerous organisms, often streptococci or staphylococci ) [2]. It is known that the vagina is normally populated by lactobacilli, which break down glycogen, which is rich in vaginal epithelial cells, to form lactic acid. Thus, an acidic environment is constantly maintained in the woman’s lower genital tract, which prevents the establishment and growth of pathogenic microflora. To maintain normal conditions and the protective function of the vagina, a large number of lactobacilli are necessary, so their share in its biocenosis is 95–98%. For various reasons listed below, lactic acid bacilli are displaced and replaced by other microorganisms. This situation facilitates the colonization of the vagina by pathogenic microorganisms - causative agents of sexually transmitted infections, but in most cases there is a change to nonspecific microflora. It includes bacteria that live on the skin of the perineum, perianal folds, and in the lower part of the urethra. They freely occupy a new habitat, multiply intensively, but cannot perform the functions of normal microflora. Their enzyme system is different from that of lactobacilli and does not break down glycogen to form lactic acid. Nonspecific microflora causes a number of disturbances in the metabolic and immune processes of the vagina as a whole. The level of production of protective immunoglobulin A decreases, which prevents pathogenic agents from attaching to the vaginal epithelium. Epithelial cells partially adsorb opportunistic bacteria on their surface and are intensively desquamated, which is associated with the appearance of discharge in BV. Lactobacilli are replaced mainly by anaerobes - bacteria that function without access to oxygen. Some of the products of their metabolism - volatile fatty acids and amino acids - are broken down in the vagina into volatile amines, which have a characteristic fishy odor. The described changes lead to a shift in vaginal pH from acidic to alkaline values. This entails progressive changes in the protein, carbohydrate, mineral and lipid metabolism of epithelial cells. Their production and mucus production increase, which clinically manifests itself as heavy discharge - the main symptom of BV. It should be noted that there is no inflammatory reaction in the walls of the vagina, and all changes are only functional in nature. Currently, a detailed study of the cultural and biochemical properties of representatives of vaginal biopsy specimens has led to the transformation of knowledge about the types of disorders of vaginal normocenosis and its infectious pathology [3]. So, BV is not a sexually transmitted infection
and does not have a single pathogen, which is why it is otherwise called “nonspecific vaginosis.” The root cause is a change in the vaginal environment, which entails disturbances in microbiocenosis. The microflora that replaces lactobacilli can be different and is most often represented by associations of opportunistic bacteria. Among them, the following groups are distinguished: bacteroids; peptococci; peptostreptococci; megaspheres; leptotrichia; atopobium; gardnerella; mycoplasma. It is also worth noting that disturbances of the vaginal microcenosis occur in 45–86% of patients in gynecological hospitals and lead to infectious complications after surgical interventions on the pelvic organs and contribute to the occurrence of diseases of the internal organs. By damaging the biological barrier, they increase several times the likelihood of infection with sexually transmitted pathogens. The growth of lactobacilli, as a rule, is excessive - their number in vaginal secretions reaches 1010 per 1 ml. However, comfortable conditions for their reproduction arise only after the influence of certain factors of the external or internal environment of the body [4].

The main causes of BV can be divided into 2 large groups.

Internal (endogenous): hormonal imbalance with a predominance of progesterone; atrophy of the vaginal mucosa; intestinal dysbiosis; immune disorders in the body. External (exogenous): long-term treatment with antibiotics; drug immunosuppression (taking cytostatics, glucocorticoids); radiation therapy of tumors; foreign objects in the vagina (hygienic tampons, pessaries, contraceptive diaphragms, rings); use of spermicides, frequent douching; failure to comply with personal hygiene rules. All of these factors in one way or another disrupt the normal functioning of the vaginal mucosa or cause the death of a large number of lactobacilli. Thus, a niche is freed up for opportunistic microflora, and it immediately occupies it. Despite the fact that the disease is not a sexually transmitted infection, its occurrence is often associated with sexual intercourse, especially when changing partners. Signs of BV in women develop on average one day after sexual intercourse without a barrier method of contraception. If the cause of the disease was the use of antibiotics and other medications, changes in hormonal levels (menopause), then the symptoms of BV develop regardless of sexual activity. According to modern concepts, one of the key links in the pathogenesis of BV is the ability of etiologically significant bacteria to form biofilms [2]. A biofilm is a microbial community in which cells are attached to any surface and/or to each other and are enclosed in an interbacterial matrix of extracellular polymeric substances synthesized by them; bacteria in biofilms have altered physiological properties [5]. Biofilm microflora is more resistant to adverse factors of a physical, chemical and biological nature compared to free-floating (planktonic) bacteria. Under such conditions, bacteria are resistant to ultraviolet radiation, dehydration, viruses, antibiotics and immune defense factors. The stability factor of biofilms is the mucus-polymer layer produced immediately after adhesion and including lipopolysaccharides, proteoglycans, glycoproteins, endopolysaccharides, similar to the substance of the cell wall, glycocalyx and bacterial capsules [5]. Recent studies indicate that BV exists as a polymicrobial biofilm infection [6, 7]. It is believed that Gardnerella vaginalis
is the first to attach to the vaginal epithelium and then serves as a “scaffold” for the attachment of other bacteria.
R. Alveset al. [8] identified 30 species of bacteria associated with BV and, in model experiments, characterized their virulence, defined as high adhesion, cytotoxicity, and a predisposition to form biofilms. It was shown that most bacteria associated with BV tended to grow as biofilms, but G. vaginalis had the highest virulence (60–90%), and Atopobium vaginae had the lowest.
The diagnosis of BV is established after collecting the patient’s medical history, studying her complaints, examining her in a gynecological chair and obtaining laboratory data.
In favor of BV, they say: age - sexually active women of reproductive age are most often affected; relationship with a change of partner, treatment of other diseases, surgical intervention; moderate or mild severity of clinical signs of the disease. During the examination, the doctor assesses the condition of the vagina, cervix, and external genitalia. With nonspecific changes, the mucous membrane is pink, not inflamed, and unevenly covered with secretions. In acute BV they are white-gray, with an unpleasant odor. If the disease has become chronic and lasts for several years, the discharge changes its color to yellowish-green, becomes thicker, more viscous, resembles cottage cheese or has a foamy appearance. During the examination, the gynecologist measures the vaginal pH with an indicator strip: with BV, its value is above 4.8–5.0. It is also worth noting the Nugent criteria - one of the main diagnostic systems for BV, which, however, in the light of new data on the “lactobacillary-free” type of vaginal microflora has shortcomings. Thus, to characterize the microbiota, the number of lactobacilli relative to BV, the associated bacterial morphotypes, is assessed. Indeed, women with a predominance of Lactobacillus spp
. they do not have BV in the vaginal biopsy. However, the conclusion that a small number of lactobacilli or their absence clearly confirms the presence of BV is incorrect [2]. Laboratory diagnosis of BV involves microscopy of stained vaginal smears. Key cells are found in them - epithelial cells of the mucous membrane with microbial bodies adhered to their surface. The cell takes on a granular appearance, its boundaries become fuzzy and dotted. Also, microscopy reveals a sharp decrease in the number of lactobacilli, up to complete disappearance from the population [2, 9, 10]. Instead, nonspecific microflora is found: single cocci, streptococci, small bacilli. Bacteriological seeding of secretions is carried out in rare cases when it is necessary to accurately determine the composition of the altered microflora. Currently, the gold standard for diagnosing BV is real-time polymerase chain reaction.

Treatment of BV

It is known that bacteria in biofilms respond to antibiotic therapy differently than planktonic bacteria, since the intercellular matrix of the biofilm can bind or not allow and/or inactivate antibiotics [7, 8]. In this regard, the formation of biofilms in BV is considered one of the main causes of persistent and recurrent BV [7, 8]. The search for drugs capable of penetrating biofilms and destroying them seems to be an urgent task. In vitro
data indicate the ability of lactobacilli to effectively destroy biofilms [7], which allows us to consider the combination of antibacterial drugs with probiotics as a promising approach to the treatment of BV.
The following regimens are recommended for the treatment of BV: European recommendations for the management of patients with pathological vaginal discharge, published by the International Union against Sexually Transmitted Infections - IUSTI (International Union against Sexually Transmitted Infections)/WHO in 2011: metronidazole (gel 0.75%) 5 g intravaginally for 5 days or clindamycin (2% cream) 5 g intravaginally at bedtime for 7 days, or clindamycin per os 300 mg twice a day for 7 days [11]. 2010 Centers for Disease Control and Prevention (CDC) recommendations: metronidazole 500 mg orally bid for 7 days or metronidazole (0.75% gel) 5 g vaginally at night for 5 days, or clindamycin (2% cream) 5 g vaginally at night for 7 days [12]. We carried out a study, the purpose
of which was to compare subjective and laboratory parameters before the study and 14 days after using the drug metronidazole and miconazole (combined drug Metromicon-Neo® (JSC Avexima, Russia) in the treatment of BV.

Material and methods

A study was conducted at the Medsi CDC on Krasnaya Presnya, in which 40 women aged 20–45 years with disorders of the vaginal microcenosis took part. The diagnosis was established on the basis of complaints, an outpatient test to determine the level of acidity of the vaginal contents and the results of a dynamic microscopic examination. The study drug was Metromicon-Neo®, which is available in the form of vaginal suppositories containing 500 mg of metronidazole and 100 mg of miconazole. Metromicon-Neo® has antibacterial, antiprotozoal and antifungal effects.

Mechanism of action of Metromicon-Neo®:

Metronidazole belongs to the 5-nitroimidazoles and is a drug with a bactericidal type of action that exhibits tropism (the ability to interact) with deoxyribonucleic acid (DNA). The mechanism of action is the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with the DNA of microbial cells, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria. Active against protozoa: Trichomonas vaginalis, Entamoeba histolytica
, as well as obligate anaerobic bacteria: gram-negative -
Bacteroides spp
.
(including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella spp;
(Prevotella bivia, Prevotella buccae, Prevotella disiens) , gram-positive -
Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp:, Mobiluncus spp.
and facultative anaerobe -
Gardnerella vaginalis.
Aerobic microorganisms are insensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), metronidazole acts synergistically with antibiotics, with a positive result against ordinary aerobes.
Miconazole is an azole derivative antifungal agent. When used intravaginally, it is active mainly against Candida albicans
. The fungicidal and fungistatic effects of miconazole are caused by inhibition of the biosynthesis of ergosterol in the membrane and plasma membranes of fungi, changes in the lipid composition and permeability of the cell wall, which causes the death of the fungal cell. Indications for use: vaginal candidiasis; trichomonas vaginitis, BV; mixed vaginal infection.

Research results

Before treatment, patients were mainly concerned about the presence of vaginal discharge with an unpleasant odor, and less frequently complained of burning, itching and discomfort in the genital area (Table 1).

Before treatment, all women studied had a vaginal pH of more than 5.0. When microscopy of vaginal smears, the microflora was mainly represented by cocci, a large number of key cells were found, the presence of a large amount of epithelium was detected in 12.5% of cases (Table 2).

All women received Metromicon-Neo® vaginal suppositories, 1 suppository in the morning and at night for 7 days. After 2 weeks Subjective and microscopic findings were assessed. As a result, it was shown that after treatment the patients had a significant reduction in the number of complaints (Table 3).

After treatment, all patients had vaginal pH ≤4.5. According to microscopic examination of vaginal smears, normalization of its microflora was observed (Table 4).

Thus, with the use of the drug Metromicon-Neo®, positive treatment results were noted (clinical picture data, microscopic examination) and good tolerability of the drug.

Conclusion

Based on the data obtained, we can conclude that Metromicon-Neo® can be recommended for the treatment of BV.
The use of combined antimicrobial drugs at the initial stages of the development of BV leads to a reduction in the risk of formation of pathological biofilms, thereby reducing the frequency of disease relapses. Information about the authors:
Yulia Eduardovna Dobrokhotova - Doctor of Medical Sciences, Professor, Head of the Department of Obstetrics and Gynecology, Faculty of Medicine. Federal State Budgetary Educational Institution of Higher Education Russian National Research University named after. N.I. Pirogov of the Russian Ministry of Health. 117997, Russia, Moscow, st. Ostrovityanova, 1. Ivanova Irina Igorevna - obstetrician-gynecologist, gynecologist-endocrinologist. CDC "Medsi" on Krasnaya Presnya. 123242, Russia, Moscow, st. Krasnaya Presnya, 16. Contact information: Ivanova Irina Igorevna, e-mail: [email protected] . Financial transparency: none of the authors has a financial interest in the materials or methods presented. conflict of interest . The article was received on August 23, 2018.
About the authors : Yulia E. Dobrokhotova - Doctor of Medical Science, professor Head of Department of Obstetrics and Gynecology, Medical Faculty, NI Pirogov Russian National Research Medical University.
1, Ostrovityanova str., Moscow, 117997, Russian Federation. Irina I. Ivanova - obstetrician-gynecologist, gynecologist-endocrinologist. CDC “Medsi in Krasnaya Presnya”. 16, Krasnaya Presnya str., Moscow, 123242, Russian Federation. Contact information: Irina I. Ivanova, e-mail: [email protected] . Financial Disclosure: no author has a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 08/23/2018.

Pharmacokinetics

The drug has 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 secretions, seminal fluid, breast milk. Binding to blood proteins is weak and does not exceed 10-20%. With normal bile formation, the concentration of metronidazole in bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

Metronidazole is excreted by the kidneys - 63% of the dose, 20% of the drug is excreted unchanged. The half-life of metronidazole is 6-7 hours. Renal clearance is 10.2 ml/min.

In patients with impaired renal function, after repeated administration of the drug, accumulation of metronidazole in the blood serum may be observed. Therefore, in patients with severe renal failure, the frequency of taking metronidazole should be reduced.

Indications for use

Protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis).

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

Infections caused by Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, fallopian tube and ovarian abscess, vaginal vault infections).

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

Indications

Treatment of protozoal infections: intestinal and extraintestinal amebiasis, trichomoniasis.
Infections caused by gram-negative anaerobes of the Bacteroidaceae family: brain and lung abscesses, necrotizing pneumonia, infections of the osteoarticular system, bacterial endocarditis and sepsis.
The drug is effective against clostridial flora, which causes infections of the genitourinary system and infections of the abdominal organs.
Metronidazole is used in gastroenterology for the treatment of gastritis, gastric and duodenal ulcers associated with H. pylori.
Prophylactic use during operations on the colon and gynecological interventions.

Contraindications

- hypersensitivity to metronidazole or other nitroimidazole derivatives;

— organic lesions of the central nervous system (including epilepsy);

- liver failure (in case of large doses);

— leukopenia (including history);

— I trimester of pregnancy,

- lactation period.

Carefully

Prescribe with caution for kidney and liver diseases (renal/liver failure).

II and III trimesters of pregnancy - only for health reasons.

Use during pregnancy and breastfeeding

Metronidazole should not be prescribed in the first trimester of pregnancy; in the future it should be used only if the potential benefit of the drug for the mother outweighs the possible risk to the fetus.

Since metronidazole passes into breast milk, reaching concentrations similar to those in plasma, it is recommended to stop breastfeeding during treatment with the drug.

special instructions

Long-term use of the drug should preferably be carried out under the control of peripheral blood parameters.

IV administration of a solution for infusion is indicated for patients in whom oral administration of the drug is impossible. For mixed infections, metronidazole infusion solution can be used in combination with parenteral antibiotics without mixing the drugs with each other.

When administered intravenously, it should not be mixed with other drugs. When using the drug, an exacerbation of candidiasis may occur.

Drinking alcohol during the course of therapy is strictly prohibited (a disulfiram-like reaction may develop: cramping abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).

When using the drug, slight leukopenia may occur, so it is advisable to monitor the blood picture (the number of leukocytes) at the beginning and at the end of therapy.

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

The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires cessation of treatment.

May immobilize treponemes and lead to a false-positive Nelson test. When treating trichomonas vaginitis in women and trichomonas urethritis in men, it is necessary to abstain from sexual activity. Simultaneous treatment of sexual partners is mandatory. After treatment for trichomoniasis, control tests should be carried out during 3 consecutive cycles before and after menstruation.

When carrying out therapy for more than 10 days - only in justified cases, with strict monitoring of the patient and regular monitoring of laboratory blood parameters. If a longer course of therapy is necessary due to the presence of chronic diseases, the balance between the expected effect and the potential risk of complications should be carefully weighed.

Instructions for use of the drug metronidazole

Inside, with a glass of water.
The daily dose is divided into 3 doses for adults, and 2 doses for children 6-15 years old. For trichomoniasis infection, 2 treatment regimens are used: 2 g of the drug once or 0.250 g twice a day, course 10 days.

When Helicobacter pylori is irradiated, metronidazole is combined with penicillin antibacterial drugs to suppress drug resistance. The daily dose of metronidazole is 1.5 g.

Metronidazole in the treatment of intestinal amebiasis is used in a daily dose of 1.5 g.

For acute amoebiasis, the daily dose is 2.250 g. The daily dose for children is 0.5 g.

Treatment of extraintestinal forms of amebiasis requires combination with tetracycline antibacterial drugs. The daily dose of metronidazole is 2.5 g in adults and 0.5 g in children.

Prevention of complications after surgical interventions involves taking 0.750 - 1.5 g of the drug per day for 4 days before surgery and 0.750 in the postoperative period for a week.

Directions for use and doses

Intravenous infusion.

Intravenous administration of metronidazole is indicated for severe infections, as well as in the absence of the possibility of taking the drug orally.

For adults and children over 12 years of age, the single dose is 500 mg, the rate of intravenous continuous (jet) or drip administration is 5 ml per minute. The interval between injections is 8 hours. The duration of treatment is determined individually. The maximum daily dose is no more than 4 g. According to indications, depending on the nature of the infection, a transition to maintenance therapy with oral forms of metronidazole is carried out.

For children under 12 years of age, metronidazole is administered at 7.5 mg/kg body weight in 3 doses at a rate of 5 ml per minute.

To prevent anaerobic infection before planned surgery on the pelvic organs and urinary tract for adults and children over 12 years of age, metronidazole is prescribed as an infusion at a dose of 500-1000 mg, on the day of surgery and the next day - at a dose of 1500 mg / day (500 mg every 8 ocloc'k). After 1-2 days, they usually switch to maintenance therapy with oral forms of metronidazole.

For patients with severe renal impairment (creatinine clearance less than 30 ml/min) and/or liver, the daily dose of metronidazole is 1000 mg; (multiplicity of administration is 2 times).

Metronidazole solution d/inf 5mg/ml 100ml No.1

Compound

Active substance: metronidazole - 5 mg Excipients: sodium chloride - 8.0 mg, citric acid monohydrate - 0.44 mg, sodium hydrogen phosphate dodecahydrate - 1.8 mg, water for injection - up to 1 ml.

Pharmacokinetics

Distribution: the drug has 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 secretions, seminal fluid, breast milk . Penetrates the blood-brain and placental barrier.

Volume of distribution: adults - approximately 0.55 l/kg, newborns - 0.54-0.81 l/kg. Bonding with plasma proteins is 10-20%.

With intravenous administration of 500 mg of metronidazole over 20 minutes to patients with anaerobic infection, the concentration of the drug in the blood serum was 35.2 μg/ml after an hour, 33.9 μg/ml after 4 hours, 25.7 μg/ml after 8 hours . With normal bile formation, the concentration of metronidazole in bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

Metabolism: About 30-60% of metronidazole is metabolized in the body by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects

Elimination: half-life (T1/2) with normal liver function - 8 hours (from 6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns born at a gestational age of 28-30 weeks - approximately 75 hours, 32-35 weeks - 35 hours, 36-40 weeks - 25 hours. 60-80% is excreted by the kidneys (20% unchanged), through the intestines - 6-15%. Renal clearance is 10.2 ml/min. In patients with impaired renal function, after repeated administration of the drug, accumulation of metronidazole in the blood serum may be observed. Therefore, in patients with severe renal failure, the frequency of taking metronidazole should be reduced. Metronidazole and its main metabolites are quickly removed from the blood during hemodialysis (T1/2 is reduced to 2.6 hours). During peritoneal dialysis, it is excreted in small quantities.

Indications for use

Metronidazole is recommended for the treatment of infections caused by microorganisms sensitive to the drug:

protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis).
infections caused by Bacteroides spp. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus): infections of bones and joints, infections of the central nervous system (CNS), including meningitis, brain abscess, bacterial endocarditis, pneumonia , empyema and lung abscess, sepsis.
infections caused by Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, fallopian tube and ovarian abscess, vaginal vault infections).

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

Contraindications

Hypersensitivity to metronidazole or other nitroimidazole derivatives, organic lesions of the central nervous system (including epilepsy), leukopenia (including a history), liver failure (if large doses are prescribed), first trimester of pregnancy;
lactation period. Carefully:

Pregnancy (II and III trimesters) - only for health reasons, renal and/or liver failure.

Directions for use and doses

Intravenous stream or drip.

Intravenous administration of metronidazole is indicated for severe infections, as well as in the absence of the possibility of taking the drug orally.

For children under 12 years of age, metronidazole is administered at 7.5 mg/kg body weight in 3 doses at a rate of 5 ml per minute.

For children under 12 years of age, it is recommended to administer metronidazole intravenously by drip according to the same regimen in a single dose of 7.5 mg/kg body weight. The maximum daily dose in children under 12 years of age is 22.5 mg/kg body weight.

For patients with severe renal impairment (creatinine clearance less than 30 ml/min) and/or liver, the daily dose of metronidazole is 1000 mg, the frequency of administration is 2 times a day. Metronidazole, solution for infusion, is not recommended to be mixed with other medications!

Storage conditions

In a dry place, protected from light, at a temperature from 2°C to 30°C.

Keep out of the reach of children.

Best before date

2 years. Do not use after the expiration date indicated on the package.

special instructions

Prescribe with caution for kidney and liver diseases.
During the treatment period, ethanol intake is contraindicated (the development of disulfiram-like reactions is possible: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).
Long-term use of the drug is preferably carried out under the control of peripheral blood parameters.
With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.
The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires cessation of treatment.
May immobilize treponemes and lead to a false-positive Nelson test.

Description

Antimicrobial and antiprotozoal agent.

Dosage form

Transparent, colorless or greenish-yellow solution.

Pharmacodynamics

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action of metronidazole is the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole interacts with the DNA of microbial cells, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

The drug exhibits high activity against Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as against obligate anaerobes (spore-forming and non-spore-forming) - Bacteroides spp. (B. fragilis. B. ovatus, B. distasonis, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains of Eubacterium.

Side effects

Very common - >10%; frequent - >1% and <10%; uncommon - >0.1% and <1%; rare - >0.01% and <0.1%; very rare - <0.01%.

From the digestive system: rarely - epigastric pain, nausea, vomiting, diarrhea, constipation, intestinal colic, loss of appetite, anorexia, taste disturbance, unpleasant “metallic” taste in the mouth, dry oral mucosa, glossitis, stomatitis; very rarely - abnormal results of tests for the functional state of the liver, cholestatic hepatitis, jaundice, pancreatitis;

From the central nervous system: with long-term use very rarely - headache, dizziness, incoordination, ataxia, peripheral neuropathy, increased excitability, irritability, depression, sleep disturbance, drowsiness, weakness, confusion, hallucinations, convulsions, encephalopathy;

From the genitourinary system: very rarely - burning sensation in the urethra, vulvovaginal candidiasis, dysuria, cystitis, polyuria, urinary incontinence, pain in the vagina, red-brown coloring of urine.

Allergic reactions: very rarely - skin rash, itching, urticaria, erythema multiforme, congestion, fever;

From the musculoskeletal system: very rarely - arthralgia, myalgia;

From the hematopoietic organs: rarely - leukopenia, agranulocytosis, neutropenia, thrombocytopenia, pancytopenia.

Local reactions: thrombophlebitis (pain, hyperemia or swelling at the injection site).

Other: flattening of the T wave on the electrocardiogram (ECG); very rarely - ototoxicity, pustular rashes, gynecomastia.

Use during pregnancy and breastfeeding

Metronidazole crosses the placenta, so the drug should not be prescribed in the first trimester of pregnancy; in the future it should be used only if the potential benefit of the drug for the mother outweighs the possible risk to the fetus.

Since metronidazole passes into breast milk, reaching concentrations similar to those in plasma, it is recommended to stop breastfeeding during treatment with the drug.

Interaction

Warfarin and other indirect anticoagulants. Metronidazole enhances the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.
Disulfiram (Esperal). Concomitant use may lead to the development of various neurological symptoms, so metronidazole should not be prescribed to patients who have taken disulfiram within the last two weeks. Similar to disulfiram, it causes ethanol intolerance.
Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its concentration in the blood serum and an increased risk of side effects.
The simultaneous administration of drugs that stimulate microsomal oxidation enzymes in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.
Lithium. In patients receiving long-term treatment with lithium drugs in high doses, when taking metronidazole, the concentration of lithium in the blood plasma may increase and symptoms of intoxication may develop.
The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.
When taking metronidazole and cyclosporine in combination, an increase in the concentration of cyclosporine in the blood plasma may be observed.
Metronidazole reduces the clearance of fluorouracil, which may increase the toxicity of the latter.
When used concomitantly, metronidazole may increase plasma concentrations of busulfan.
It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide).

Overdose

Symptoms: nausea, vomiting, dizziness, in more severe cases - ataxia, paresthesia and convulsions.

Treatment: symptomatic and supportive therapy. There is no specific antidote.

Impact on the ability to drive vehicles and operate machinery

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Side effect

Gastrointestinal disorders:

epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, “metallic” taste in the mouth, loss of appetite, anorexia, dry oral mucosa, constipation, pancreatitis (reversible cases), change in tongue color/“coated tongue” (from - for the growth of fungal microflora).

Immune system disorders:

angioedema, anaphylactic shock.

Nervous system disorders

: peripheral sensory neuropathy, headache, convulsions, dizziness, the development of encephalopathy and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus, tremor) has been reported, which are reversible after discontinuation of metronidazole, aseptic meningitis.

Mental disorders:

psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

Visual disorders:

transient visual impairments, such as diplopia, myopia, blurred outlines of objects, decreased visual acuity, impaired color perception; neuropathy/optic neuritis.

Blood and lymphatic system disorders

: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Disorders of the liver and biliary tract

: increased activity of “liver” enzymes (aspartate aminotransferase, alanine aminotransferase, 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 antibacterial agents, cases of liver failure requiring liver transplantation have been observed.

Skin and subcutaneous tissue disorders

: rash, itching, skin flushing, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Renal and urinary tract disorders

: staining of urine in a brownish-reddish color, caused by the presence of a water-soluble metabolite of metronidazole in the urine, dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General and administration site disorders

: fever, nasal congestion, arthralgia, weakness, thrombophlebitis (pain, hyperemia or swelling at the injection site).

Laboratory and instrumental data

: flattening of the T wave on the electrocardiogram.

Interaction with other drugs

Metronidazole for intravenous infusion is not recommended to be mixed with other medications!

When using metronidazole for injection, there is little interaction with other drugs, but caution should be exercised when used simultaneously with certain drugs.

Warfarin and other indirect anticoagulants.

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

Disulfiram.

Concomitant use may lead to the development of various neurological symptoms, so metronidazole should not be prescribed to patients who have taken disulfiram within the last two weeks.

Cimetidine

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

Simultaneous use of drugs that stimulate microsomal oxidation enzymes in the liver ( phenobarbital, phenytoin

) may accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

In patients receiving long-term treatment with lithium

in high doses, when using metronidazole, it is possible to increase the concentration of lithium in the blood plasma and develop symptoms of intoxication.

The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.

With the combined use of metronidazole and cyclosporine

An increase in the concentration of cyclosporine in the blood plasma may be observed.

Metronidazole reduces the clearance of fluorouracil,

which may cause an increase in the toxicity of the latter.

When used concomitantly, metronidazole may increase plasma concentrations of busulfan.

It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide).

Metronidazole is incompatible with ethanol (disulfira-like reactions develop when used together).