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

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

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. AT. 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 minimum inhibitory concentration for these strains is 0.125-6.25 μg / ml.

In combination with amoxicillin shows activity against Helicobacter pylori (amoxycycline inhibits 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.

Causes sensitization to alcohol (disulfiramoid action).

The prevalence of acquired resistance may vary depending on the geographical region and over time, so when choosing antibacterial therapy, local resistance information should be taken into account.

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 (FROM_mOh) is from 6 to 40 μg / ml, depending on the dose. The time to reach the maximum concentration (TFROM_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 hours (from 10 to 29 hours), in newborns: those born at the gestation period of 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% unchanged), through the intestine - 6-15%.

Kidney clearance - 10.2 ml / min. In large patients with renal dysfunction 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 (half-life (T_1/2) is reduced to 2.6 h). When peritoneal dialysis is withdrawn in small quantities.

Eating does not affect the absorption of the drug.

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. AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus), infections of bones and joints, central nervous system (CNS) infections, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess.

Infections caused by the species Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), infections of small organs (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection).

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori (complex therapy).

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

Contraindications:

Hypersensitivity to imidazoles, as well as to nitroimidazole derivatives.

Leukopenia (including in the anamnesis).

Organic lesions of cerebral palsy (including epilepsy).

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

Pregnancy.

Lactation period.

Children up to 10 years.

Carefully:

Hepatic encephalopathy, acute and chronic peripheral and central nervous system (risk of weighty neurological symptoms), renal failure.

Dosing and Administration:

Inside, before or after eating, drink plenty of water.

- with intestinal amebiasis apply for 7 days to 1500 mg per day in 3 divided doses. In acute amoebic dysentery - The daily dose is 2250 mg per day, divided into 3 doses. Children from 10 to 15 years - 500 mg per day, divided into 2 doses.

- with abscess of the liver and other extraintestinal forms of amoebiasis the maximum daily dose is 2500 mg per day, divided into 3 doses for 3-5 days, in combination with the use of trastcyclin antibiotics and other therapies. Children from 10 to 15 years - 500 mg per day, divided into 2 doses.

- with trichomoniasis in women (urethritis and vaginitis) metronidazole appoint once in a dose of 2 g or in the form of course treatment for 10 days 250 mg twice a day.

- with trichomoniasis in men (urethritis) metronidazole appoint once in a dose of 2 g or in the form of course treatment for 10 days 250 mg twice a day.

- with pseudomembranous colitis - 500 mg 3-4 times a day. The duration of treatment is determined by the doctor.

- for eradication Helicobacter pylory - 500 mg 3 times a day for 7 days (as part of combination therapy, for example, combination with amoxicillin 2.25 g per day). In the treatment of anaerobic infection, the maximum daily dose is 1.5-2 g.

- for prevention of postoperative complications - 750 to 1500 mg per day in 3 divided doses 3-4 days before surgery. In 1-2 days after the operation (when ingestion is already allowed) - 750 mg of the drug per day for 7 days.

With severe renal dysfunction (creatinine clearance less than 10 ml / min) 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 (impaired coordination and synergy of movements, ataxia, dysarthria, gait disorders, nystagmus, tremor), which are reversible after the withdrawal of metronidazole. aseptic meningitis.

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

Vision disorders: 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 genotocellular 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 metabolite metromidazole, 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, hyperemia or swelling at the injection site) (for parenteral dosage forms).

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

Overdose:

Symptoms: vomiting, ataxia, disorientation.

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

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).

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

Given the profile of side effects (dizziness, visual impairment and others), 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:

Tablets, 250 mg.

Packaging:

10 tablets per contour cell pack.

For 1 or 2 contour packs together with instructions for medical use in a pack of cardboard.

Storage conditions:

In a place protected from light and moisture, at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-000751

Date of registration:30.07.2010 / 20.05.2015

Expiration Date:Unlimited

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Representation: & nbspBORISOVSKIY FACTORY OF MEDPREPARATES, OJSCBORISOVSKIY FACTORY OF MEDPREPARATES, OJSC

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)