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 by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group reacts with the deoxyribonucleic acid (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 (P.bivia, P.buccae, P.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 not sensitive 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 and placental barrier. The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg.

The maximum concentration of the drug in the blood (C_mOh) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration (TC_mOh) - 1-3 hours. Communication with plasma proteins - 10-20%.

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 h (from 10 to 29 hours), in newborns: those born at the time of pregnancy - 28-30 weeks - about 75 hours, respectively, 32-35 weeks - 35 hours, 36-40 weeks - 25 hours. 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 (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, giardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomoniasis urethritis.

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

Infections caused by the species Bacteroides, including group AT. fragilis, species Clostridium, 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 after surgical operations), skin and soft tissue infections,

Infections caused by the species Bacteroides, including group AT. fragilis and species Clostridium: sepsis.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori, alcoholism.

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

Radiation therapy of patients with tumors - as a radiosensitizer, 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:BVariability (II-III trimesters), renal / hepatic insufficiency.

Pregnancy and lactation:

During lactation it is recommended to stop breastfeeding.

Dosing and Administration:

Inside, during or after a meal, (or squeezed milk), without chewing.

With trichomoniasis - 250 mg twice a day for 10 days or 400 mg twice a day for 5-8 days.

Women need to be additionally appointed metronidazole in the form of vaginal suppositories or tablets. If necessary, you can repeat the course of treatment or increase the dose to 0.75-1 g / day. Between the courses should be a break in 3-4 weeks with the implementation of repeated control laboratory tests. An alternative scheme of therapy is the appointment of 2 g once to the patient and his sexual partner.

Children 2-5 years - 250 mg / day; 5-10 years - 250-375 mg / day, more than 10 years - 500 mg / day. The daily dose should be divided into 2 divided doses. The course of treatment is 10 days.

With giardiasis - 500 mg twice a day for 5-7 days.

Children under 1 year - 125 mg / day, 2-4 years - 250 mg / day, 5-8 years - 375 mg / day, over 8 years - 500 mg / day (in 2 divided doses). The course of treatment is 5 days.

With giardiasis - 15 mg / kg / day in 3 divided doses for 5 days.

Adults: with asymptomatic amoebiasis (if a cyst is detected), the daily dose is 1-1.5 g (500 mg 2-3 times a day) for 5-7 days.

With chronic amebiasis daily dose - 1.5 g in 3 divided doses for 5-10 days, with acute amoebic dysentery - 2.25 g in 3 doses until the symptoms stop.

With liver abscess - The maximum daily dose - 2.5 g in 1 or 2-3 doses, for 3-5 days, in combination with antibiotics (tetracyclines) and other methods of therapy.

Children 1-3 years - 1/4 of the adult dose, 3-7 years - 1/3 of the adult dose, 7-10 years - 1/2 dose of the adult.

With balantidiasis - 750 mg 3 times a day for 5-6 days.

With ulcerative stomatitis adults are prescribed 500 mg twice a day for 3-5 days; children in this case, the drug is not shown.

With pseudomembranous colitis - 500 mg 3-4 times a day.

For eradication of Helicobacter pylory - 500 mg 3 times a day for 7 days (as part of combination therapy, for example, combination with amoxicillin 2.25 g / day).

In the treatment of anaerobic infection the maximum daily dose is 1.5-2 g.

In the treatment of chronic alcoholism prescribe 500 mg / day for a period of up to 6 (not more) months.

For the prevention of infectious complications - 750-1500 mg / day in 3 divided doses 3-4 days before surgery, or once 1 g in the first day after the operation. In 1-2 days after the operation (when already allowed ingestion) - 750 mg / day for 7 days. In severe renal dysfunction (CC less than 10 ml / min), the daily dose should be halved.

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" ( 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 disturbances, nystagmus, tremor) that are reversible after metroni-dazole cancellation, aseptic 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 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 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 (for oral and parenteral dosage forms), thrombophlebitis (pain, congestion or swelling at the injection site) (for parenteral dosage forms).

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

Interaction:

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

Similarly to 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.

With simultaneous administration with lithium preparations, the concentration of the latter in the plasma and the development of symptoms of intoxication may increase.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

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 worsening of 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 trichomoniasis therapy, control tests should be performed for three consecutive cycles before and after menstruation.

After treatment of giardiasis, if symptoms persist, after 3 to 3 weeks, 3 feces should be analyzed at intervals of several days (in some successfully treated patients lactose intolerance caused by invasion may persist for several weeks or months, recalling the symptoms of giardiasis).

Effect on the ability to drive transp. cf. and fur:Given the risk of developing such adverse reactions as confusion, dizziness, hallucinations, visual impairment, it is recommended during treatment to refrain from driving, from practicing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Tabletki, 250 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10 tablets in a contour non-cellular package of paper with polyethylene coating.

For 20 tablets in cans of polymer complete with lids, or in polystyrene cans.

Each jar or 2 contour packs, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:

Store in a dry place, protected from light and out of reach of children, at a temperature not exceeding +25 ° C.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N002615 / 01-2003

Date of registration:29.07.2008

Expiration Date:Unlimited

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Representation: & nbspVALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)