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, as well as Gram-negative anaerobes Bacteroides spp. (incl. AT. fragilis, B. aboutvatus, B.distasonis, 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.

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.

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: lungs, kidneys, liver, skin, cerebrospinal fluid, brain and spinal cord, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk. Penetrates through the blood-brain and placental barrier. Distribution: adults - approximately 0.55 l / kg.

The maximum concentration of metronidazole 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 alcohol damage of the liver - 18 hours (10 to 29 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 application can be observedcumulation of metronidazole in the blood serum (therefore, in patients with severe renal failure, the frequency of intake should be reduced).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T_1/2 is reduced to 2.6 hours). When peritoneal dialysis is withdrawn in small quantities.

Indications:

Infectious-inflammatory diseases caused by sensitive Metronidazole by microorganisms:

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. 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, pleural empyema, lung abscess;
- infections caused by species 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).

Pseudomembranous colitis (associated with the use of antibiotics).

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

Prevention of postoperative infections (mainly surgery on the large intestine, gynecological operations).

Contraindications:

Hypersensitivity to metronidazole, other components of the drug, to imidazoles, as well as to the derivatives of nitroimidazole; organic lesions of the central nervous system (including epilepsy); leukopenia (including in the anamnesis); pregnancy; the period of breastfeeding; hepatic failure (in the case of the appointment of large doses); children under 3 years.

Carefully:

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

Pregnancy and lactation:

Use during pregnancy is contraindicated.

If you need to use the drug during lactation, you should decide whether to abort breastfeeding.

Dosing and Administration:

Inside, during or after eating, without chewing. Drink plenty of water.

Adults:

Anaerobic infections

Usually, treatment is started with intravenous infusions of metronidazole followed by a switch to taking the drug Metronidazole inside.

500 mg 3 times a day. The duration of treatment is up to 7 days.

Trichomoniasis

In trichomoniasis in women (urethritis and vaginitis), the drug is used once in a dose of 2 g or in the form of course treatment for 10 days: 250 mg 2 times a day. For trichomoniasis in men (urethritis), the drug is used once in a dose of 2 g or as a course of treatment for 10 days: 250 mg 2 times a day.

Pseudomembranous colitis

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

Intestinal amebiasis

1500 mg per day for three doses for 7 days. In acute amoebic dysentery, the daily dose is 2,250 mg divided into three doses.

Abscess of the liver and other extraintestinal forms of amoebiasis

The maximum daily dose is 2500 mg, divided into 3 doses, for 3-5 days, in combination with tetracycline antibiotics and other therapies.

Gastritis or duodenal ulcer associated with Helicobacter pylori

For 500 mg 3 times a day as part of a combination therapy, for example, with amoxicillin.

Prevention of postoperative infections

750-1500 mg per day in 3 divided doses 3-4 days before surgery. 1-2 days after the operation (when already allowed ingestion) - 750 mg per day for 7 days.

With renal insufficiency (creatinine clearance less than 10 ml / min) daily dose should be reduced by 2 times.

Children over 3 years old:

Anaerobic infections

20-30 mg / kg per day.

Intestinal amebiasis

30-40 mg / kg per day in three divided doses.

Abscess of the liver and other extraintestinal forms of amoebiasis

30-40 mg / kg per day in three divided doses.

Side effects:

Disorders from the digestive system: diarrhea, epigastric pain, decreased appetite, anorexia, nausea, vomiting, constipation, "metallic" taste in the mouth, dryness of the oral mucosa, glossitis, stomatitis, pancreatitis.

Disturbances from the nervous system: dizziness, development of encephalopathy (eg confusion) and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disturbance, nystagmus and tremor), irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations , peripheral sensory neuropathy, aseptic meningitis.

Disorders from the kidneys and urinary tract: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color.

Immune system disorders: angioedema, anaphylactic shock.

Disturbances on the part of the organ of sight: transient visual impairments, such as diplopia, myopia, vagueness of the contours of objects, reduced visual acuity, violation of color perception. Neuropathy / optic neuritis.

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

Disturbances from the liver and bile ducts: impaired liver function, increased activity of liver transaminases, alkaline phosphatase, development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice, liver failure, requiring liver transplantation (in patients treated with metronidazole in combination with other antimicrobial agents).

Disturbances from the skin and subcutaneous tissues: a rash, itching, flushing of the skin, hives, pustular skin rash.

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

Other: nasal congestion, fever, arthralgia.

Overdose:

Symptoms: nausea, vomiting, ataxia, convulsions, peripheral neuropathy.

Treatment: symptomatic therapy. There is no specific antidote.

Interaction:

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

Simultaneous use with ethanol leads to the occurrence of disulfiram-like reactions (skin flushing, vomiting, tachycardia).

Simultaneous use with disulfiram can lead to the development of various neurologic symptoms (the interval between appointments is at least 2 weeks).

With the simultaneous administration of metronidazole with cyclosporine, the serum concentration of cyclosporine can increase.

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

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

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

Special instructions:

In the period of treatment, the intake of ethanol is contraindicated (possible development disulfiram-like reaction: 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 parameters of peripheral blood. With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

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.

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.

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, 500 mg.

Packaging:

For 10, 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

By 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets in cans of polymeric for medicines.

One bank or 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 contour cell packs, together with the instruction for use, are placed with a cardboard package (bundle).

Storage conditions:

In the 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 the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002568

Date of registration:07.08.2014

Expiration Date:07.08.2019

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)