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

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. 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 reacts with the DNA of a cell of microorganisms, 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 (Prevotella bivia, Prevotella buccae, Prevotella disiens) and some Gram-positive microorganisms (sensitive strains Eubacterium, 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 inhibits the development of resistance to metronidazole ).

Metronidazole is insensitive to aerobic microorganisms and facultative anaerobes, 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 disulfiram-like reactions, stimulates reparative processes.

Pharmacokinetics:

It has a high penetrating power, 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 barrier 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 of the drug in the blood (TS_mOh) - 1-3 hours. Communication with plasma proteins - 10-20%.

With intravenous administration of 500 mg for 20 min C_mOh in the blood serum after 1 h - 35.2 μg / ml. The concentration of the drug in the blood after 4 hours is 33.9 μg / ml, after 8 hours 25.7 μg / ml; C_min with subsequent administration of 18 μg / ml. TS_mOh - 30-60 minutes, the therapeutic concentration persists for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after IV introduction can significantly exceed the concentration in the plasma.

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.

Half-life of blood (T_1/2) with normal liver function - 8 hours (from 6 to 12 hours), with alcoholic liver damage -18 hours (from 10 to 29 hours), in newborns: those born at the time of pregnancy - 28-30 weeks - about 75 hours, 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_1/2is 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. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection of bones and joints, infections of the central nervous system, incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and abscess of lungs sepsis.

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

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori.

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

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

Contraindications:

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

Carefully:

- II and III trimesters of pregnancy - only for life reasons;

renal / hepatic insufficiency.

Pregnancy and lactation:

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

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

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

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

For the prevention of anaerobic infection before the planned operation on the pelvic organs and urinary tract adults and children over 12 years Metronidazole is administered in the form of infusions in 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 hours).After 1-2 days usually go to maintenance therapy with oral forms of metronidazole.

For patients with severe renal dysfunction (creatinine clearance less than 30 ml / min) and / or liver The daily dose of metronidazole is 1000 mg (multiplicity of intake 2 times a day).

Metronidazole for intravenous fluids should not be mixed with other medications!

Side effects:

From the digestive system: diarrhea, decreased appetite, 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 urinary system: dysuria, cystitis, polyuria, incontinence, candidiasis. the staining of urine in red-brown color causes metabolite metronidazole, has no clinical significance).

Local Reactions: thrombophlebitis (pain, flushing or swelling at the injection site).

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

Overdose:

The specific antidote is unknown. It is necessary to carefully monitor the patient's condition, make gastric lavage, carry out usual emergency measures, ensure sufficient fluid intake. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

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

Similarly, disulfiram causes intolerance to ethanol.

The simultaneous use of metronidazole with disulfiram can lead to the development of various neurological symptoms (the interval between appointments is at least 2 weeks).

Metronidazole for intravenous administration is not recommended to be mixed with other drugs.

Cimetidine suppresses the metabolism of metronidazole, which can lead to an increase in its concentration in the blood serum 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 reception with drugs Li+ The concentration of the latter in the plasma and the development of symptoms of intoxication may increase.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

Special instructions:

During the treatment period, ethanol intake is contraindicated (development of disulfiram-like reactions is possible: abdominal pain of spastic nature, 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 therapy with trichomoniasis, control tests should be performed for 3 consecutive cycles before and after menstruation.

After treatment of giardiasis, if symptoms persist, 3 feces analysis should be performed at intervals of several days after 3-4 weeks (in some successfully treated patients lactose intolerance caused by invasion can persist for several weeks or months, recalling the symptoms of giardiasis).

Form release / dosage:Solution for infusion, 5 mg / ml.

Packaging:

100 ml in bottles of low-density polyethylene. Each vial is in a plastic bag, in a cardboard box with instructions for use.

For hospitals: 20, 24, 50 or 100 vials together with instructions for use in a cardboard box.

Storage conditions:

In a dry, dark place, out of the reach of children, at a temperature not exceeding 30 ° C. Do not freeze.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012706 / 01

Date of registration:09.09.2009 / 10.06.2013

Expiration Date:Unlimited

The owner of the registration certificate:Aquarium EnterpriseAquarium Enterprise India

Manufacturer: & nbsp

AQUARIUS ENTERPRISES India

Representation: & nbspAquarium EnterpriseAquarium EnterpriseIndia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)