Metrogil - 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, as well as Gram-negative anaerobes Bacteroides spp. (including W. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). The MIC 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 / 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 intravenously administered 500 mg of the drug for 20 minutes, the maximum concentration (C_mOh) in serum is: 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 with subsequent administration - 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 with a gestation period of 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 may occur. in the serum (therefore, in patients with severe renal failure, the frequency of intake should be reduced).

Metronidazole and the major metabolites are rapidly removed from the blood under 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 (including trichomonas vaginitis, trichomonas urethritis).

Infections, called 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, pleural empyema and lung abscess, sepsis.

Infectionscaused by species Clostridium spp., Peptococcus and Peptostreptococcus: infection of the abdominal cavity (peritonitis, liver abscess), infection of the pelvic organs (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, vaginal vaginal infection).

Prevention postoperative complications (especially interference on the colon, near-rectal area, appendectomy, gynecological operations).

Contraindications:

Hypersensitivity to metronidazole or components included in the preparation, as well as to other derivatives of nitroimidazole; I trimester of pregnancy, lactation period, organic lesions of the central nervous system (including epilepsy), blood diseases (including in the anamnesis), liver failure (in the case of the appointment of large doses).

Carefully:

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

Pregnancy and lactation:

- I trimester of pregnancy is contraindicated;

- nursing mothers - according to the indications, with the simultaneous termination of breastfeeding.

Dosing and Administration:

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

Adults and children over 12 years of age the initial dose is 0.5 - 1 g intravenously drip (infusion duration - 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. With the improvement of the patient's condition, according to the indications, a transition is made to the maintenance medication inside at a dose of 400 mg 3-5 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 intravenously 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.

Side effects:

Disorders from the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, metallic taste in the mouth, decreased appetite, anorexia, dryness of the oral mucosa, constipation, pancreatitis (reversible cases), discoloration of the tongue / "lipped tongue" (from for proliferation of fungal microflora).

Immune system disorders: angioedema, anaphylactic shock.

Impaired 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 disturbance, nystagmus, tremor) that are reversible after metronidazole withdrawal, aseptic meningitis.

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

Disorders from the side of the organ of vision: transient visual impairments, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

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

Disorders from the liver and bile ducts: increased activity of "hepatic" enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice; in patients treated with metronidazole in combination with other antibacterial agents, cases of hepatic insufficiency that required liver transplantation were observed.

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 metronidazole metabolite, 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 electrocardiogram.

Overdose:

Symptoms: nausea, vomiting, ataxia; when receiving as a radiosensitizing agent - convulsions, peripheral neuropathy.

Treatment: there is no specific antidote, symptomatic and supportive therapy.

Interaction:

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

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 inhibits metronidazole metabolism, which can lead to an increase in its serum concentration 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.

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. After therapy with trichomoniasis, control tests should be performed for 3 consecutive cycles before and after menstruation.

With prolonged therapy, it is necessary to monitor the picture of peripheral blood.

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.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment, care must be taken when driving vehicles and when engaging in other potentially dangerous activities that require increased concentration and speed of psychomotor reactions (dizziness, impaired consciousness, hallucinations, convulsions, impaired coordination of movements, ataxia).

Form release / dosage:

Solution for intravenous administration 5 mg / ml.

Packaging:100 ml per bottle of low density polyethylene. 1 bottle in a cellophane wrap is placed in a cardboard box together with instructions for use.

Storage conditions:

At a temperature of no higher than 30 ° C, in a place protected from light. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N011666 / 01

Date of registration:07.06.2010 / 10.05.2017

Expiration Date:Unlimited

The owner of the registration certificate:Unik Pharmaceutical Laboratories Unik Pharmaceutical Laboratories India

Manufacturer: & nbsp

UNIQUE PHARMACEUTICAL Laboratories India

Representation: & nbsp"UNIC PHARMACEUTICAL LABORATORY (branch of the company" JB Chemicals and Pharmaceuticals Ltd. ")""UNIC PHARMACEUTICAL LABORATORY (branch of the company" JB Chemicals and Pharmaceuticals Ltd. ")"India

Information update date: & nbsp11.05.2018

Illustrated instructions

Instructions

Metrogil® (Metrogyl®)