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

Tablets are white or white with a yellowish-greenish shade of color, flat-cylindrical, with a bevel,with risk on one side and labeling "R" or without it - on the other.

Pharmacotherapeutic group:Antimicrobial and antiprotozoal drug

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Metronidazole is 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.

It is active against Trichomonas vaginalis, Entamoeba histolytica, as well as gram-negative anaerobes Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains of 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, it shows activity against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

Metronidazole is not sensitive 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.

Pharmacokinetics:

Ingestion metronidazole quickly and almost completely absorbed (about 80% per hour). The intake of food does not affect the absorption of metronidazole. Bioavailability is not less than 80%. After oral administration of metronidazole at a dose of 500 mg, its concentration in the blood plasma is 10 μg / ml after 1 hour, 13.5 μg / ml after 3 hours. Binding to blood proteins is insignificant and does not exceed 10-20%. Metronidazole quickly penetrates into tissues (lungs, kidneys, liver, skin, bile, cerebrospinal fluid, saliva, seminal fluid, vaginal secret), into breast milk and passes through the placental barrier. About 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

40-70% of metronidazole is excreted by the kidneys (unchanged - about 35% of the dose taken). The half-life is 8-10 hours.

In patients with impaired renal function with a course of metronidazole, an increase in serum concentration is possible.

Indications:

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

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

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

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori.

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 (incl.in anamnesis), organic lesions of the central nervous system (CNS) (including epilepsy), liver failure (in the case of large 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:

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, over 10 years - 500 mg / day. The daily dose should be divided into 2 divided doses. The course of treatment is 10 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.

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

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

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.

With severe renal dysfunction (creatinine clearance less than 10 ml / min) daily dose should be halved.

Side effects:

Violations cabout the side of the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, metallic taste in the mouth, decreased appetite, anorexia, dryness of the mucosal membrane of the pta cavity, constipation, pancreatitis (reversible cases), discoloration of the tongue / "lipped tongue" ( because of the growth of fungal microflora). Impaired immune system: angioedema, anaphylactic shock.

Violations from the nervous systems: 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 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 the contours of objects, reduced visual acuity, violation of color perception; Neuropathy optic neuritis.

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

Disturbances from the liver and bile ducts: rise 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 in combination with other antibacterial agents, there were cases of liver failure, requiring liver transplantation.

Disturbances from the skin and subcutaneous tissues: rash, itching, skin hyperemia, urticaria, pustular skin rash, Stivens-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: fever, nasal congestion, arthralgia, weakness.

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 serum concentrations 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 npotand reception of ethanol is possible (development of a disulfiram-like reaction is possible: spastic abdominal pain, vomiting, headache, sudden rush of blood to the face).

In combination with amoxicillin, it is not recommended to use patients younger 18 let.

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

With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

Occurrence 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.

When treating trichomonas vaginitis in women and trickmonadic thepetrita the men. It is necessary to abstain from sexual activity. Obligatory simultaneous treatment of sexual partners. Treatment does not stop during menstruation. After therapy with trichomonias, control samples should be taken for three consecutive cycles before and after the change.

Metronidazole can cause severe hypersensitivity reactions that threaten the patient's life,including angioedema, anaphylactic shock, Stevens-Johnson syndrome, toxic epidermal necrolysis. If these reactions develop, stop metronidazole therapy immediately and begin appropriate therapy.

In patients receiving metronidazole, it is possible to develop psychotic reactions (confusion, hallucinations, depression) with possible harm to their health after the first dose, especially in patients with a history of mental illness. In the event that the reactions described above appear, discontinue taking the drug and take appropriate measures.

Simultaneous use of metronidazole and disulfiram or busulfan is not recommended.

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

Given the profile of adverse affects (dizziness, transient visual impairment, etc.), it is recommended during treatment to refrain from driving and other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, 250 mg.

Packaging:

For 8, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil or paper packaging.

2 contiguous cell packs of 10 tablets or 3 contour packs of 8 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-002069

Date of registration:10.02.2011 / 28.03.2017

Expiration Date:Unlimited

The owner of the registration certificate:UPDATE OF PFC, CJSC UPDATE OF PFC, CJSC Russia

Manufacturer: & nbsp

UPDATE, PFC CJSC Russia

Representation: & nbspUPDATE OF PFC, CJSCUPDATE OF PFC, CJSC

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)