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

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

Active in relation to: Trichomonas vaginalis, Entamoeba histolytica, and gram-negative anaerobes Bacteroides spp. (in t. h. Bacteroides fragilis, Bacteroides ovatus, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., and some gram-positive anaerobes (sensitive strains 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 irradiation, causes disulfiram-like reactions.

Pharmacokinetics:

Suction: when intravenously administered 500 mg of the drug for 20 minutes, the maximum concentration of metronidazole in the serum was 35.2 μg / ml an hour later, 33.9 μg / ml after 4 hours, and 25.7 μg / ml after 8 hours.

Distribution: the drug 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. Binding to plasma proteins - 10-20%. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

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 born at the gestation period of 28-30 weeks - approximately 75 hours, 32- 35 weeks - 35 hours, 36-40 weeks - 25 hours.

Metabolism and excretion: excretion of metronidazole is performed by the kidneys - 63% (20% is excreted unchanged); intestines - 6-15%. The renal clearance is 10.2 ml / min.

In patients with impaired renal function after repeated administration of the drug cumulation of metronidazole in serum can be observed (therefore, the frequency of metronidazole should be reduced in patients with severe renal insufficiency).

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 When peritoneal dialysis is withdrawn in significant quantities.

Indications:

- Protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis).

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

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

- 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 to metronidazole, to other derivatives of nitroimidazole, other components of the drug.

- Organic lesions of the central nervous system (including epilepsy).

- Leukopenia (including anamnesis).

- Hepatic insufficiency (in the case of the appointment of large doses).

- Pregnancy (first trimester).

- Breastfeeding period.

Carefully:

- Pregnancy (II and III trimesters), only for vital indications.

- Hepatic and / or renal insufficiency.

- Children under 12 years.

- Acute and chronic diseases of the peripheral and central nervous system (risk of weighting of neurological symptoms).

Pregnancy and lactation:

A drug Metronidazole contraindicated in the first trimester of pregnancy and lactation.

In the II and III trimester of pregnancy, the drug is used only if the intended benefit to the mother exceeds the potential risk to the fetus.

Dosing and Administration:

Intravenously sprayed or drip. Intravenous administration of the drug Metronidazole It is indicated in case of severe infection, and also when there is no possibility of taking the drug inside.

Adults and children over 12 years of age in the initial dose of 500-1000 mg 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 duration of treatment is determined individually. The maximum daily dose is not more than 4 g. According to the indications, depending on the nature of the infection, the transition to maintenance therapy with metronidazole drugs for oral administration is carried out.

Children under the age of 12 years injected at a dose of 7.5 mg / kg body weight every 8 hours at a rate of 5 ml / min. The maximum daily dose in children under 12 years of age is 22.5 mg / kg body weight.

For the prevention of anaerobic infection before the planned operation on the pelvic organs and urinary tract adults and children over 12 years 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. Children under 12 years of age are recommended to administer the drug Metronidazole intravenously drip on the same schedule in a single dose of 7.5 mg / kg body weight.

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 application - 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 hour before the start of irradiation.

Apply before each irradiation session for 1-2 weeks. In the remaining period of radiation treatment, the drug Metronidazole do not apply. The maximum single dose should not exceed 10 grams, the course dose should be 60 g.

Side effects:

Disorders from the gastrointestinal tract: pain in the epigastrium, nausea, vomiting, diarrhea, glossitis, stomatitis, taste disorders ("metallic" taste in the mouth), decreased appetite, anorexia, dryness of the oral mucosa, constipation, pancreatitis (reversible cases), discoloration / "lined tongue" (because of 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, aseptic meningitis.

Disorders from 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: 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 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 an electrocardiogram.

Overdose:

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

Treatment: symptomatic and supportive therapy. There is no specific antidote.

Interaction:

Metronidazole, a solution for infusions, is not recommended to be mixed with other medicinal products.

Metronidazole enhances the effect of indirect anticoagulants (warfarin), which leads to an increase in the time of prothrombin formation.

Simultaneous application with disulfiram can lead to the development of various neurologic symptoms (the interval between use is at least 2 weeks). Similarly disulfiram causes intolerance to ethanol.

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 use 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 the simultaneous use of metronidazole with lithium preparations may increase the concentration of the latter in blood plasma and the development of symptoms of intoxication.

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

Sulfonamides enhance the antimicrobial effect of metronidazole.

With the simultaneous use of metronidazole with cyclosporin can increase the concentration of cyclosporine in the blood serum.

Metronidazole reduces clearance fluorouracil, leading to an increase in its toxicity.

Metronidazole increases concentration busulfan in blood plasma, which can lead to the development of severe toxic effects of busulfan.

Special instructions:

In the period of treatment, the use of ethanol is contraindicated (development of disulfiram-like reactions is possible: abdominal pain of a spastic nature, nausea, vomiting, headache, "tide" of blood to the face).

With prolonged use of the drug should monitor blood levels. With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

The drug should be used as directed by a doctor and if symptoms such as ataxia, dizziness, convulsions or any other deterioration in the neurological status of patients develop, treatment should be discontinued.

When treating trichomonas vaginitis in women and trichomoniasis in men, it is necessary to abstain from sexual intercourse. It is necessary to simultaneously treat sexual partners.

Treatment does not stop during menstruation. After trichomoniasis therapy, control tests should be performed for 3 consecutive cycles before and after menstruation.

It is necessary to take into account that metronidazole can immobilize treponemy, which leads to a false positive test of Nelson. Stains urine in a dark color.

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

Given a number of side effects from the central nervous system, dizziness, visual impairment, it is recommended during the treatment to refrain from driving, from practicing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

To 50 ml in bottles of colorless glass I hydrolytic class, hermetically sealed with rubber stoppers, crimped aluminum caps.

For 1, 2, 5 or 10 bottles together with the instruction for use are placed in a pack of cardboard box.

Storage conditions:

In the dark place at a temperature of not less than 8 ° C and not higher than 25 ° C. Do not freeze.

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:LP-002758

Date of registration:15.12.2014

Expiration Date:15.12.2019

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

R-PHARM, JSC Russia

Representation: & nbspR-PHARM, JSC R-PHARM, JSC Russia

Information update date: & nbsp09.09.2016

Illustrated instructions

Instructions

Metronidazole (Metronidazole)