Metronidazole-ESCOM - 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 in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains of Eubacterium spp., Clostridium spp., Peptococcus niger, 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.

To Metronidazole insensitive 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 disulfiramoid-like reaction.

Pharmacokinetics:

Absorption is high (bioavailability is not less than 80%). 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 connection with plasma proteins is 10-20%.

When administered intravenously 500 mg for 20 minutes, the maximum concentration (C_mOh) of the preparation in the blood after 1 hour - 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml; minimum concentration (C_min) of the drug in the blood with subsequent administration of 18 μg / ml. Time to reach the maximum concentration (TC_m_Oh) of the drug in the blood - 30-60 minutes, the therapeutic concentration persists 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.

The half-life (T_1/2) with normal liver function - 8 hours (6 to 12 hours), with alcoholic liver damage - 18 hours (10 to 29 hours), in newborns: those born at the gestational age - 28-30 weeks - about 75 hours, 32-35 week - 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 (including trichomonas vaginitis, trichomonas urethritis), giardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis:

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

- infections caused by species Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (endometritis, endomyometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection);

- pseudomembranous colitis (associated with the use of antibiotics);

- gastritis or ulcer of the duodenum associated with Helicobacter pylori;

- prevention of postoperative complications (especially interference on the colon, pararectal area, appendectomy, gynecological operations);

- radiation therapy of patients with tumors - as a radiosensitizing drug, in cases where tumor resistance is due to 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:

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:

Parenteral.

Adults and children over 12 years in an initial dose of 0.5-1 g intravenously drip (the duration of infusion is 30-40 minutes), 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 transition is made to the maintenance dose 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.

With purulent-septic diseases usually spend 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 is not more than 1 g,the frequency of reception is 2 times a day.

As a radiosensitizing drug injected intravenously drip at the rate of 160 mg / kg or 4-6 g / m² body surface for 0.5-1 hour 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 radiation, a drop introduction of 5% solution of dextrose, Hemodesum or 0.9% solution of sodium chloride.

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, 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.

Overdose:

Symptoms: nausea, vomiting, ataxia, in severe cases - peripheral neuropathy and epileptic seizures.

Treatment: symptomatic, specific antidotes are absent.

Interaction:

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

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

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).

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.

Form release / dosage:

Solution for intravenous administration, 5 mg / ml.

Packaging:

For 100 ml in glass bottles for blood, transfusion and infusion preparations with a capacity of 100 ml.

For 1 bottle together with instructions for medical use put in a pack of cardboard.

For 28 bottles with an equal number of instructions for medical use are placed in boxes of corrugated cardboard with gaskets and gratings - "nests" of corrugated cardboard (for hospitals).

Storage conditions:

In the dark place at a temperature of 8 ° C to 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-000948

Date of registration:18.10.2011

Expiration Date:18.10.2016

The owner of the registration certificate:ESKOM NPK, OAO ESKOM NPK, OAO Russia

Manufacturer: & nbsp

ESKOM NPK, OAO Russia

Representation: & nbspESKOM NPK, OAOESKOM NPK, OAO

Information update date: & nbsp10.09.2016

Illustrated instructions

Instructions

Metronidazole-ESCO (Metronidazole-ESKOM)