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

Excipients: sodium chloride - 7.9 mg, citric acid monohydrate 0.23 mg, sodium hydrophosphate (disodium anhydrous phosphate) 0.48 mg, water for injection up to 1 ml.

Description:

Transparent liquid, with a greenish-yellow hue.

Pharmacotherapeutic group:Antimicrobial and antiprotozoal drug

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group of intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group interacts with the DNA of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active in relation to:

- protozoa: Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Lamblia spp .;

- anaerobic bacteria: Bacteroides spp. (in t.h. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Clostridium spp., Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp.), Prevotella spp. (in t.h. Prevotella bivia, Prevotella buccae, Prevotella disiens), Veillonella spp .;

- Gardnerella vaginalis.

The MIC for these strains is 0.125-6.25 μg / ml.

Metronidazole in combination with amoxicillin is active against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

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 sensitization to alcohol (disulfiram-like action), stimulates reparative processes.

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 maximum concentration is from 6 to 40 μg / ml depending on the dose. The time to reach the maximum concentration is 1-3 hours. The connection with plasma proteins is 10-20%.

With intravenous administration of 500 mg for 20 minutes, the maximum serum concentration in 1 hour is 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours 25.7 μg / ml; the minimum concentration for subsequent administration is -18 μg / ml.The time to reach the maximum concentration is 30-60 minutes, the therapeutic concentration is maintained for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration 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 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 gestation period - 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% in unchanged form), 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 the main metabolites are quickly removed from the blood during hemodialysis (the elimination half-life is 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, trichomonas vaginitis, trichomoniasis urethritis, giardiasis (giardiasis), balantidiasis, cutaneous leishmaniasis;

- infections caused by anaerobic microorganisms:

- 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 lung abscess;

- infections caused by species Bacteroides, including group Bacteroides fragilis, as well as species Clostridium, Eubacterium, Peptococcus and Peptostreptococcus: infections of the abdominal cavity (peritonitis, intra-abdominal abscess, liver abscess), pelvic infection (endometritis, endomyometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection after surgery, pelvic abscess), skin and soft tissue infections (incl. postoperative wounds);

- infections caused by species Bacteroides, including group Bacteroides fragilis and species Clostridium: sepsis;

- prevention of postoperative infectious complications (especially with interventions on the colon and rectum, near-rectal area,with gynecological operations and organs of the abdominal cavity, with appendectomy), performed before the operation, intraoperatively and after surgery;

- radiation therapy of patients with tumors - as a radiosensitizing agent, 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:

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

Pregnancy and lactation:During lactation it is recommended to stop breastfeeding.

Dosing and Administration:

Adults and children over 12 years of age in the initial dose of 0.5-1 g intravenously drip (duration of infusion - 30-60 minutes), and then every 8 hours 500 mg at a rate of 5 ml / min. The course of treatment is 7 days, but if necessary, intravenous administration is continued for a longer time. The maximum daily dose is 4 g. With the improvement of the patient's condition, according to the indications, a transition is made to the maintenance intake inside the dose of 400-500 mg 3-4 times / day.

Children under the age of 12 years metronidazole 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 the prevention of postoperative infectious complications - adults and children over 12 years of age prescribe intravenously drip at a dose of 15 mg / kg (approximately 1 g to a patient with a body weight of 70 kg) 1 hour before the start of the operation (duration of infusion is 30-60 minutes), then repeat intravenous drip of metronidazole at a dose of 7.5 mg / kg (approximately 500 mg to a patient with a body weight of 70 kg) every 6 hours after the first administration of the drug. 1-2 days after the operation (when it is already allowed inside) - go to metronidazole inward at a single dose of 7.5 mg / kg (approximately 500 mg to a patient with a body weight of 70 kg) every 6-8 hours for 7 days.

Patients with chronic renal insufficiency and with 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.

Side effects:

Disorders from the gastrointestinal tract: pain in the epigastrium, nausea, vomiting, diarrhea, glossitis, stomatitis "metallic" taste in pty, loss of appetite, anorexia, dry eating and diet of the oral cavity, constipation, pancreatitis (reversible cases),change in the color of the tongue / "lined tongue" (due to the growth of fungal microflora).

Immune system disorders: angioedema, anaphylactic shock.

Disturbances from the nervous system: peripheral sensory neuropathy, headache, convulsions, dizziness, reported on the development of encephalopathy and subacute cerebellar syndrome (disruption of coordination and synergy of movements, ataxia, dysarthria, gait disorders, nystagmus, tremor) that are reversible after metronidazole withdrawal, acupuncture meningitis.

Disorders of the psyche: psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

Disturbances on the part of the organ of sight: transient visual impairment, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

Violations of the blood and lymphatic system: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Disturbances from the liver and bile ducts: an increase in the activity of hepatic enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, the development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice, in patients treated with metronidazole and combinations with other antibacterial agents, there were cases of liver failure , which required the transplantation of the liver.

Disturbances from the skin and subcutaneous tissues: rash, itching, skin hyperemia, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract: staining of 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 site of administration: fever, nasal congestion, arthralgia, weakness, thrombophlebitis (pain, flushing or swelling at the injection site).

Laboratory and instrumental data: flattening of the T wave on the electrocardiogram.

Interaction:

Metronidazole for intravenous administration is not recommended to be mixed with other medicines!

Strengthens the action indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Similarly to disulfiram, causes intolerance ethanol.

Simultaneous application with disulfiram can lead to the development of various neurological symptoms (the interval between appointment - at least 2 weeks).

Cimetidine inhibits 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 that stimulate 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 lithium may increase the concentration of the latter in the plasma and the development of symptoms of intoxication.

It is not recommended to combine with nondepolarizing muscle relaxants (vecuronium bromide).

Sulfonamides enhance the antimicrobial effect of metronidazole.

Possible simultaneous administration in the treatment of infections of mixed anaerobic-aerobic etiology Metronidazole solution for infusion and antibacterial drugs from groups penicillins, cephalosporins, aminoglycosides, fluoroquinolones, and clindamycin, chloramphenicol and vancomycin.

Special instructions:

During the period of treatment, ethanol intake is contraindicated (a disulfiram-like reaction may develop: spastic abdominal pain, 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.

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

Packaging:

To 100 ml in bottles of orange or colorless glass or in bottles of orange or colorless glass

1 bottle or bottle is placed in a pack of cardboard with instructions for use and suspension polymer or without suspension.

35 bottles or bottles with an equal number of pendants or without pendants, with 5 instructions for use in a box of corrugated cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 "C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N002101 / 02

Date of registration:06.05.2008 / 14.04.2015

Expiration Date:Unlimited

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole-AKOS (Metronidazole-AKOS)