Antiprotozoal and antimicrobial drug. Derivative of 5-nitroimidazole. The mechanism of action is the biochemical restoration of the 5-nitro group of intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group interacting with the DNA of the cell of microorganisms inhibits the synthesis of their nucleic acids, which leads to the death of bacteria. Active against Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., as well as obligate anaerobes Bacteroides spp. (including Bacteroides fragilis. Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus). Fusobacterium spp., Veillonela spp., Prevotella (P. bivia, P. buccae, P. disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The MIC for these strains is 0.125-6.25 μg / 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.
Increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like effect), stimulates reparative processes.
In most body cells and fluids, including lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk, reaches bactericidal concentrations, crosses the blood-brain and placental barrier . Distribution volume (UA): adults – approximately 0.55 l / kg, newborns – 0.54-0.81 l / kg. Communication with plasma proteins – 10-20%.
The maximum concentration in the blood (Cmax) is reached after 30-60 minutes, the therapeutic concentration is maintained for 6-8 hours. The minimum concentration of blood products (Cmin) with subsequent administration is 18 μg / ml. With normal bile formation, the concentration of metronidazole in bile after intravenous (iv) administration can significantly exceed the plasma concentration.
About 30-60% of metronidazole is metabolized in the body by hydroxylation, oxidation and glucuronidation. The main metabolite (2-hydroxymetronidazole) also has an antiprotozoal and antimicrobial effect.
The half-life (T1/2) with normal liver function is 8 hours (from 6 to 12 hours), with alcoholic liver damage – 18 hours (from 10 to 29 hours), in newborns: those born with a gestational age of 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 intestines – 6-15%. Renal clearance – 10.2 ml / min. In patients with impaired renal function, repeated administration may result in cumulation of metronidazole in serum (therefore, in patients with severe renal failure, the frequency of administration should be reduced). Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T Ѕ reduced to 2.6 hours). With peritoneal dialysis, it is excreted in small quantities.
Indications for use
Protozoal infections: extraintestinal amoebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, hyardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis, 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), incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess.
Infections caused by Bacteroides species, including the B. fragilis group, Clostridium, Peptococcus and Peptostreptococcus species: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, endomyometritis, abscesses of the fallopian tubes and ovaries, vaginal vaginal infections after surgery) , skin and soft tissue infections, sepsis.
Pseudomembranous colitis (associated with the use of antibiotics).
Gastritis or duodenal ulcer associated with Helicobacter pylori.
Prevention of postoperative complications (especially interventions on the colon, periorectal region, appendectomy, gynecological surgery). Radiation therapy of patients with tumors (as a radiosensitizing agent, in cases when the resistance of the tumor is due to hypoxia in the tumor cells). Alcoholism.
Dosage and administration
Adults and children over 12 years of age in an initial dose of 0.5-1 g i/v drip (duration of infusion -30-40 min), and then every 8 hours at 500 mg at a rate of 5 ml / min. With good tolerance, after the first 2-3 infusions, they switch to jet administration. The course of treatment is 7 days. If necessary, i/v administration is continued for a longer time. The maximum daily dose is 4 g. According to the indications, a transition to a maintenance oral intake in a dose of 400 mg 3 times / day is carried out. Children under the age of 12 are prescribed according to the same scheme in a single dose of 7.5 mg / kg.
With purulent-septic diseases, usually 1 course of treatment is carried out.
For preventive purposes, adults and children over 12 years of age are given i/v in a drip of 0.5-1 g on the eve of the operation, on the day of the operation and the next day – 1.5 g / day (500 mg every 8 hours). After 1-2 days, they switch to maintenance therapy inside. For patients with chronic renal failure (CRF) and creatinine clearance (CC) less than 30 ml / min and / or liver failure, the maximum daily dose is not more than 1 g, the frequency of administration is 2 times a day. As a radiosensitizing agent, they are injected i/v in a dose of 160 mg / kg or 4-6 g / m2 of the body surface 0.5-1 hours before the start of irradiation. Apply before each irradiation session for 1-2 weeks. In the remaining period of radiation treatment, metronidazole is not used. The maximum single dose should not exceed 10 g, course – 60 g. To remove intoxication caused by irradiation, drip administration of glucose solutions or isotonic sodium chloride solution is used.
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, irritability, weakness, insomnia, headache, cramps, hallucinations, peripheral neuropathy.
Allergic reactions: urticaria, skin rash, flushing of the skin, nasal congestion, fever, arthralgia.
From the genitourinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, urine staining in red-brown color.
Local reactions: thrombophlebitis (pain, redness or swelling at the injection site).
Other: neutropenia, leukopenia, flattening of the T wave on the ECG.
Hypersensitivity, leukopenia (including a history), organic lesions of the central nervous system (including epilepsy), liver failure (in the case of high doses), pregnancy (I trimester), lactation.
With caution – pregnancy (P-III trimesters), renal / liver failure.
For i/v administration, metronidazole is not recommended to be mixed with other drugs. The drug enhances the effect of indirect anticoagulants, which leads to an increase in the formation of prothrombin.
Like disulfiram, it causes intolerance to ethanol. The simultaneous use with disulfiram can lead to the development of various neurological symptoms (the interval between the appointment is at least 2 weeks).
Cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its concentration in 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, as a result of which its plasma concentration decreases.
With simultaneous administration with lithium preparations, the concentration of the latter in plasma and the development of symptoms of intoxication may increase.
It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide). Sulfanilamides enhance the antimicrobial effect of metronidazole.
During treatment, ethanol is contraindicated (a disulfiram-like reaction is possible: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).
In combination with amoxicillin is not recommended for patients under 18 years of age. With prolonged therapy, it is necessary to control 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 deterioration in the neurological status of patients requires discontinuation of treatment.
Can immobilize treponema and come to a false positive Nelson test. Stains urine in dark color.
In the treatment of trichomonas vaginitis in women and trichomonas urethritis in men, it is necessary to refrain from sexual activity. Be sure to simultaneously treat sexual partners. Treatment does not stop during menstruation. After treatment of trichomoniasis, control tests should be carried out for three successive cycles before and after menstruation. After treatment of giardiasis, if symptoms persist, after 3 to 4 weeks, 3 feces should be performed at intervals of several days (in some successfully treated patients, lactose intolerance caused by invasion can persist for several weeks or months, resembling symptoms of giardiasis). During lactation, it is recommended to stop breastfeeding.
Symptoms: nausea, vomiting, ataxia.
Treatment: gastric lavage, the introduction of activated charcoal (in case of taking the drug inside), hemodialysis. Metronidazole and its metabolites are well excreted during hemodialysis.
500 mg / 100 ml infusion solution in 100 ml plastic bottles or glass bottles
In a dry, dark place at a temperature of no higher than 25 ° C.
The drug should be stored out of the reach of children.
Do not use after expiration date.
Pharmacy sales terms