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 metronidazole but interacts 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 (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 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 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 barrier and placental barrier.

The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg. The maximum concentration in the blood plasma (C_mOh) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration in the blood plasma (TC_mOh) - 1-3 hours. Communication with plasma proteins - 10-20%.

When intravenously administered 500 mg for 20 minutes, the maximum concentration in the blood plasma after 1 hour is 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml; minimal concentration in blood plasma (C_min) with the subsequent administration of 18 μg / ml, the time to reach the maximum concentration in the blood plasma is 30-60 min, the therapeutic concentration is maintained for 6-8 hours.With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may 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 with normal liver function is 8 hours (6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns: those born at the gestational age - 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 of metronidazole cumulation in serum can be observed (hence patients with severe renal impairment receiving frequency to be reduced).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (the elimination half-life is reduced to 2.6 h). When peritoneal dialysis is withdrawn in small quantities.

Indications:

- Protozoal infections: extraintestinal amoebiasis,including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, giardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomonas 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, pleural empyema and lung abscess, 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).

- 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, near-rectal 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 to metronidazole or other nitroimidazole derivatives, leukopenia (including in anamnesis), organic lesions of the central nervous system (including epilepsy), hepatic insufficiency (in the case of high doses), pregnancy (I trimester), period lactation.

Carefully:

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

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

Dosing and Administration:

Intravenously.

Adults and children over 12 years of age in the initial dose of 0.5-1 g intravenously drip (duration of infusion - 30-40 min), and then every 8 hours 500 mg at a rate of 5 ml / min. With good tolerability after the first 2-3 infusions pass to a jet injection. The course of treatment is 7 days. If necessary, intravenous administration is continued for a longer time. The maximum daily dose is 4 g. According to the indications, a transfer to the maintenance dose of metronidazole is taken inside at a dose of 400 mg 3 times a day.

Children under the age of 12 years prescribe the same scheme in a single dose of 7.5 mg / kg.

When purulent-septic diseases are usually conducted 1 course of treatment.

For preventive purposes, adults and children over 12 years of age prescribe iv drip 0.5-1 g on the eve of surgery, on the day of surgery and the next day - 1.5 g / day (500 mg every 8 hours). After 1-2 days, they switch to maintenance therapy inside. Patients with chronic renal insufficiency and creatinine clearance less than 30 ml / min and / or liver failure the maximum daily dose - no more than 1 g, the frequency of reception - 2 times a day.

As a radiosensitizing drug injected iv in the drip at the rate of 160 mg / kg or 4-6 g / m2 body surface for 0.5-1 h before the start of irradiation. Apply before each irradiation session for 1-2 weeks. In the remaining period of radiation treatment metronidazole do not apply. The maximum single dose should not exceed 10 grams, the course dose should be 60 g. To remove intoxication caused by irradiation, a 5% solution of Dextrose, Hemodeza or 0.9% sodium chloride solution is used.

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, movement coordination disorders, 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, urinary incontinence, candidiasis, staining of urine in red-brown color.

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

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

Interaction:

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

Similarly, 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).

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.

Together with the admission lithium drugs may increase the plasma concentration of the latter and the development of symptoms of intoxication.

It is not recommended to combine with nondepolarizing 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 deterioration in 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 glass with a capacity of 100 ml.

1 bottle with instructions for use in a pack of cardboard.

For hospitals:

- 48 bottles with an equal number of instructions for use in a box of corrugated cardboard;

- from 1 to 48 bottles with an equal number of instructions for use in a box of corrugated cardboard.

Storage conditions:

In the dark place at a temperature of 10 ° C to 25 ° C. Freezing is not allowed.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N003078 / 01

Date of registration:18.09.2008 / 27.01.2014

Expiration Date:Unlimited

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)