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

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

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, 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.

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.Increases the sensitivity of tumors to irradiation, causes disulfiram-like reactions.

Pharmacokinetics:

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 barrier and placental barrier.

The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg. The connection with plasma proteins is 10-20%. With iv injection of 500 mg for 20 min C_mOh in the blood serum after 1 hour - 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml. TS_mOh - 30-60 minutes, the therapeutic concentration persists for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after IV introduction can significantly exceed the concentration in the plasma.

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.

T_1/2with normal liver function - 8 hours (6 to 12 hours), with alcoholic liver damage - 18 hours (10 to 29 hours), in newborns: those born at the gestational age - 28-30 weeks - about 75 hours, 32-35 week - 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 patients with impaired renal function after repeated administration, cumulation of metronidazole in serum can be observed (therefore, the frequency of administration should be reduced in patients with severe renal insufficiency).

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

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

Infections caused by the species Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), infections of the pelvic organs (endometritis, abscess of the 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 and / or to other components of the drug, leukopenia (including in anamnesis), organic lesions of the central nervous system (including epilepsy), liver failure (in the case of high doses), pregnancy (I trimester), the period of lactation.

Carefully:

Renal / hepatic insufficiency, acute and chronic diseases of the peripheral and central nervous system (risk of weighty neurological symptoms).

Pregnancy and lactation:

Contraindicated use during pregnancy (I trimester) and lactation.When pregnant (II-III trimesters) are used only if the intended benefit to the mother exceeds the potential risk to the fetus.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Intravenous (drip or jet).

Adults and children over 12 years of age in the initial dose of 0.5-1 g IV in the drip (the duration of the infusion is 30-40 minutes), and then every 8 hours at 500 mg at a rate of 5 ml / min. With good tolerability after the first 2-3 infusions pass to a jet injection. The course of treatment is 7 days. If necessary, iv administration is continued for a longer time. The maximum daily dose is 4 g. According to the indications, a transition is made to the maintenance dose inside at a dose of 400 mg 3 times a day.

Children under the age of 12 years metronidazole 7.5 mg / kg body weight is administered in three doses at a rate of 5 ml per minute. 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 pelvic organs and urinary tracts for adults and children over 12 years of age Assign iv / drip but 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 the age of 12 years it is recommended the administration of metronidazole intravenously drip on the same schedule in a single dose of 7.5 mg / kg body weight.

Patients with chronic renal insufficiency and clearance of creenatine 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 h before the start of irradiation. Apply before each irradiation session for 1-2 weeks. In the remaining period of radiation treatment metronidazole do not apply. The maximum single dose should not exceed 10 grams, the course dose should be 60 g.

To remove intoxication caused by radiation, a drop introduction of 5% solution of dextrose, Hemodesum or 0.9% solution of sodium chloride.

With tumors of the cervix, skin tumors are used in the form of local applications (3 g are dissolved in 10% solution of dimethylsulfoxide), wet tampons, which are applied topically, 1.5-2 hours before irradiation). With a poor regression of the tumor, the appliqués are carried out throughout the course of radiotherapy.With a positive dynamics of purification of the tumor from necrosis - during the first 2 weeks of treatment.

Side effects:

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

From the central nervous system: dizziness, impaired coordination of movements, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy, encephalopathy, subacute cerebellar syndrome.

Allergic reactions: urticaria, skin rash, skin hyperemia, angioedema, anaphylactic shock, itchy skin, pustular skin rash, fever, nasal congestion, arthralgia.

From the urinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color.

From the hepatobiliary system: decreased liver function (laboratory indicators), cholestatic hepatitis sometimes with jaundice.

From the hematopoiesis: agranulocytosis, thrombocytopenia.

On the part of the organs of vision: transient visual impairment: diplopia, myopia, vagueness of contours of subjects, decreased visual acuity, violation of color perception, neuropathy / neuritis of the optic nerve.

Local reactions: thrombophlebitis (pain, flushing or swelling at the injection site).

Other: neutropenia, leukopenia, aseptic meningitis, flattening of the T wave on an electrocardiogram.

Overdose:

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

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

Interaction:

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

Similarly, 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).

Metronidazole for intravenous administration is not recommended to be mixed with other drugs.

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.

Together with the admission lithium drugs may increase the plasma concentration of the latter and the development of symptoms of intoxication.

With the combined use of metronidazole and cyclosporine, an increase in the concentration of cyclosporine in the blood plasma can be observed.

Metronidazole reduces the clearance of fluorouracil, which can cause an increase in toxicity of the latter.

With simultaneous application metronidazole can increase plasma concentrations of busulfan.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

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, sudden rush of blood to the face).

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 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.

After therapy with trichomoniasis, control tests should be performed for 3 consecutive cycles before and after menstruation.

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

If there are side effects from the central nervous system, you should refrain from driving and working with potentially dangerous machines and mechanisms.

Form release / dosage:Solution for infusion, 5 mg / ml.

Packaging:

To 100 ml in polymeric containers for single-use infusion solutions made of polyolefin film.

Each container is packaged in a secondary package of metallized film. Instructions for use in the box with containers equal to the number of containers.

Containers in secondary bags are placed in boxes of corrugated cardboard.

Storage conditions:

In dry, dark place 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 expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002001

Date of registration:13.02.2013

Expiration Date:13.02.2018

The owner of the registration certificate:FIRM MEDPOLIMER, JSC FIRM MEDPOLIMER, JSC Russia

Manufacturer: & nbsp

FIRM MEDPOLIMER, JSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)