Metronidazole tablets 250mg, No. 40

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

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

• Infections caused by Bacteroides spp. (including Bacteroides fragilis), Clostridium, Peptococcus, Peptostreptococcus species: infections of the abdominal cavity (peritonitis, liver abscess), infections of the pelvic organs (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, infections of the vaginal vault after surgery), infections of the skin and soft tissues.

• Infections caused by Bacteroides spp. (including Bacteroides fragilis), Clostridium species: sepsis.

• Pseudomembranous colitis associated with antibiotic use.

• Gastritis or duodenal ulcer associated with Helicobacter pylori, alcoholism.

• Prevention of postoperative complications (especially interventions on the colon, near-rectal region, apendectomy, gynecological operations).

• Radiation therapy for patients with tumors - as a radiosensitizing agent, in cases where tumor resistance is due to hypoxia in tumor cells.

Inside, during or after meals (or with milk), without chewing.

With trichomoniasis - 250 mg 2 times a day for 10 days or 400 mg 2 times a day for 5-8 days. Women need to additionally prescribe metronidazole in the form of vaginal suppositories or tablets. If necessary, repeat the course of treatment or increase the dose to 0.75Ц1 g / day. The interval between courses of treatment is 3-4 weeks with repeated laboratory tests. An alternative scheme is a single dose of 2 g for both sexual partners. Children 2Ц5 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 doses. The course of treatment is 10 days.

With giardiasis - 500 mg 2 times a day for 5-7 days. Children under 1 year old - 125 mg / day; 2-4 years - 250 mg / day, 5-8 years - 375 mg / day, over 8 years - 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.

In asymptomatic amoebiasis (if cysts are detected) for adults, the daily dose is 1-1.5 g (500 mg 2-3 times a day) for 5-7 days.

In chronic amoebiasis, the daily dose is 1.5 g in 3 doses for 5-10 days, in acute amoebic dysentery - 2.25 g in 3 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 adult dose, 3-7 years old - 1/3 adult dose, 7-10 years old - 1/2 adult dose.

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

For ulcerative stomatitis: adults - 500 mg 2 times a day for 3-5 days; children - the drug is not indicated.

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

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

In the treatment of anaerobic infection, the maximum daily dose is 1.5Ц2 g

In the treatment of chronic alcoholism - 500 mg / day for a period of up to 6 months (no more).

For the prevention of infectious complications - 750-1500 mg / day in 3 doses 3-4 days before surgery or once 1 g on the first day after surgery. 1-2 days after surgery - 750 mg / day for 7 days.

In severe renal impairment (Cl creatinine <10 ml / min), the daily dose should be halved.

Pills

1 tab.

metronidazole 250 mg

• Hypersensitivity

• leukopenia (including history),

• organic lesions of the central nervous system (including epilepsy),

• hepatic impairment (in the case of large doses),

• pregnancy (I trimester),

• lactation period.

With caution - II Ц III trimesters of pregnancy, renal / hepatic failure.

pharmachologic effect

Antiprotozoal agent with antibacterial activity, derivative of 5-nitroimidazole. The mechanism of action consists in 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 the cell of microorganisms, inhibiting the synthesis of nucleic acids, which leads to the death of microorganisms.

Active against Trichomonas vaginalis, Entamoeba hystolitica, as well as gram-negative anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides 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 ?g / ml. In combination with amoxicillin, it is active against Helicobacter pylori (amoxicillin inhibits the development of resistance to metronidazole).

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

Pharmacokinetics

When taken orally, metronidazole is rapidly and almost completely absorbed (approximately 80% in 1 hour). Food intake does not affect the absorption of metronidazole. Bioavailability is at least 80%. After oral administration of metronidazole at a dose of 500 mg, its concentration in blood plasma is 10 ?g / ml after 1 hour, 13.5 ?g / ml - after 3 hours.

With intravenous administration of 500 mg for 20 minutes, Cmax in serum after 1 hour is 35.2 ?g / ml. The concentration of metronidazole in the blood serum after 4 hours - 33.9 ?g / ml, after 8 hours - 25.7 ?g / ml; Cmin with subsequent administration - 18 ?g / ml. Tmax - 30-60 minutes, the therapeutic concentration lasts for 6-8 hours. With normal bile formation, the concentration of metronidazole in bile after intravenous administration can significantly exceed the plasma concentration.

The binding to 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 secretions), breast milk and passes through the placental barrier.

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

40-70% of metronidazole is excreted by the kidneys (unchanged - about 35% of the dose taken). T1 / 2 - 8-10 hours

Side effect

From the digestive system: epigastric pain, nausea, vomiting, diarrhea; inflammation of the oral mucosa (glossitis, stomatitis), taste disturbances ('metallic' taste in the mouth), decreased appetite, anorexia, dryness of the oral mucosa, constipation; pancreatitis (reversible cases); discoloration of the tongue / 'coated' tongue (due to excessive growth of fungal microflora).

From the immune system: angioedema, anaphylactic shock.

From the nervous system: peripheral sensory neuropathy; headache, convulsions, dizziness. It has been reported about the development of encephalopathy (for example, confusion) and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus and tremor), which undergo a regression after discontinuation of metronidazole; aseptic meningitis.

Mental disorders: psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, hyperexcitability.

From the side of the organ of vision: transient visual impairments such as diplopia, myopia, blurred vision, decreased visual acuity, impaired color perception; neuropathy / optic neuritis.

From the side of the organ of hearing and labyrinth disorders: hearing impairment / hearing loss (including sensorineural deafness); noise in ears.

From the hematopoietic system: agranulocytosis, leukopenia, neutropenia and thrombocytopenia.

From the liver and biliary tract: increased activity of hepatic enzymes (ACT and ALT, ALP), the development of cholestatic or mixed hepatitis, hepatocellular liver damage, sometimes accompanied by jaundice. In patients treated with metronidazole in combination with other antibiotics, cases of liver failure have been observed, requiring liver transplantation.

On the part of the skin and subcutaneous tissues: rash, itching, flushing of the skin, flushing of the skin, urticaria; pustular skin rash; acute generalized exanthematous pustulosis; fixed drug rash; Stevens-Johnson syndrome, toxic epidermal necrolysis.

From the urinary system: 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 injection site: fever, nasal congestion, arthralgia, weakness.

Influence on the results of laboratory and instrumental studies: flattening of the T wave on the ECG.

Application during pregnancy and lactation

Use during pregnancy and breastfeeding is contraindicated.

Application for violations of liver function

Use in high doses is contraindicated in liver failure.

Use with caution in hepatic encephalopathy.

Application for impaired renal function

Use with caution in renal failure.

Application in children

Use is contraindicated in children under 6 years of age.

special instructions

Since the simultaneous administration of metronidazole with alcohol (ethanol) can have an effect similar to the action of disulfiram (hyperemia of the skin, flushing of the skin, vomiting, tachycardia), patients should be warned that during treatment and for at least one day after the end of the drug intake During the period of treatment, you should not consume alcoholic beverages or drugs containing ethanol.

The indications for long-term use of metronidazole should be carefully weighed and, in the absence of strict indications, its prolonged use should be avoided. If, in the presence of strict indications, the drug is used for a longer time than is usually recommended, treatment should be carried out under the control of hematological parameters (especially leukocytes) and adverse reactions, such as peripheral or central neuropathy (paresthesia, ataxia, dizziness, convulsions), upon the appearance of which treatment should be terminated.

When treating Trichomonas vaginitis in women and Trichomonas urethritis in men, it is necessary to refrain from sexual intercourse. Simultaneous treatment of sexual partners is mandatory. Treatment should not be discontinued during menstruation. After trichomoniasis therapy, control tests should be carried out for 3 successive cycles before and after menstruation.

Metronidazole should be used with caution in patients with hepatic encephalopathy, as well as in patients with acute or chronic diseases of the central or peripheral nervous system due to the possible risk of neurological deterioration.

It has been reported on the development of severe hepatotoxicity / acute hepatic failure (including fatal cases that developed very quickly after the start of treatment) in patients with Cockayne's syndrome when treated with metronidazole for systemic use. For this category of patients, metronidazole should be prescribed only after a careful assessment of the benefit / risk ratio and only in the absence of alternative treatment.

Liver function tests should be carried out before starting treatment, during therapy and after its completion until the liver function indicators reach normal values, or until the baseline values ??of these indicators are reached. If the indicators of liver function are significantly exceeded during treatment, then the drug should be discontinued.

Patients with Cockayne syndrome should be advised to immediately inform the doctor about the development of any symptoms of potential liver damage and to stop using metronidazole.

Cases of severe bullous skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis, or acute generalized exanthematous pustulosis, have been reported after taking metronidazole. With the development of symptoms or signs of these diseases, treatment with Klion should be stopped immediately.

It must be taken into account that metronidazole can immobilize treponemas, which leads to a false positive Nelson's test.

Long-term use of metronidazole must be carefully justified due to possible mutagenicity and carcinogenicity.

Influence on the ability to drive vehicles and mechanisms

Given the risk of developing such adverse reactions as confusion, dizziness, hallucinations, visual impairments, it is recommended during treatment to refrain from driving, from engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Drug interactions

It was reported about the development of psychotic reactions in patients who received simultaneously metronidazole and disulfiram (the interval between the use of these drugs should be at least 2 weeks).

With simultaneous use with ethanol, disulfiram-like reactions may occur (hyperemia of the skin, flushing of the skin, vomiting, tachycardia).

With simultaneous use with indirect anticoagulants (warfarin) - an increase in the anticoagulant effect and an increased risk of bleeding associated with a decrease in hepatic metabolism of indirect anticoagulants, which can lead to an increase in prothrombin time. In the case of the simultaneous use of metronidazole and indirect anticoagulants, more frequent monitoring of prothrombin time and, if necessary, correction of anticoagulant doses are required.

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

With the simultaneous use of metronidazole with cyclosporine, the concentration of cyclosporine in the blood plasma may increase. If necessary, the simultaneous use of metronidazole and cyclosporine should monitor the concentration of cyclosporine and creatinine in the blood plasma.

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

The simultaneous use of metronidazole with drugs that induce isoenzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) can accelerate the excretion of metronidazole, as a result of which its concentration in blood plasma decreases.

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

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

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

Sulfonamides enhance the antimicrobial effect of metronidazole.

The simultaneous use of mebendazole and metronidazole should be avoided.

Simultaneous administration of the drug with other solutions containing sodium salts can lead to sodium retention in the body.

In laboratory studies during the use of the drug, difficulties in determining the activity of AST, ALT, LDH, and the concentration of triglycerides are possible.