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

auxiliary components: sodium chloride - 9 mg, sodium dihydrogen phosphate dihydrate (sodium phosphate monosubstituted 2-water) - 3 mg, water for injection - up to 1 ml.

Description:Pa slightly yellow liquid with a greenish tinge.

Pharmacotherapeutic group:Antimicrobial and antiprotozoal drug

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group of intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group interacts 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 obligate anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., and some gram-positive microorganisms (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 (amoxicillin suppresses 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.

Increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like action).

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 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 intravenous administration of 500 mg for 20 min C_mOhin the blood serum after 1 hour - 35.2 μg / ml. Concentration of the drug in the blood after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml; C_min with subsequent administration of 18 μg / ml. TS_max - 30-60 minutes, the therapeutic concentration persists for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration 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.

Half-life (T_1/2) with normal liver function - 8 hours (6 to 12 hours), with alcohol damage of the liver - 18 hours (from 10 to 29 hours), in newborns born at term of pregnancy - 28-30 weeks - about 75 hours, 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%. In severe renal impairment (creatinine clearance less than 10 ml / min), patients can be cumulated metronidazole in serum after repeated administration, and the dose should be reduced by half.

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:

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

Infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection 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.: infection 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, paraectal area, appendectomy, gynecological operations).

Radiation therapy of patients with tumors - as a radiosensitizing drug, in cases where tumor resistance is due to 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:

Pregnancy (II-III trimesters) - only for vital indications, renal / hepatic insufficiency.

Dosing and Administration:

Intravenous administration of metronidazole is indicated in severe infections, as well as in the absence of the possibility of taking the drug inside.

For adults and children over 12 years a single dose of 500 mg, the rate of intravenous continuous (jet) or dropwise administration - 5 ml per minute. The interval between administrations is 8 hours. The duration of treatment is determined individually. The maximum daily dose is no more than 4 g. According to the indications, depending on the nature of the infection, a transition to maintenance therapy with oral forms of metronidazole is carried out.

Children under the age of 12 years metronidazole 7.5 mg / kg of body weight is administered in 3 divided doses at a rate of 5 ml per minute.

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 metronidazole prescribe in the form of infusions in a dose of 500-1000 mg, on the day of the operation and the next day - at a dose of 1500 mg / day (500 mg every 8 hours). After 1-2 days usually go to maintenance therapy with oral forms of metronidazole.

For patients with severe renal dysfunction (creatinine clearance less than 30 ml / min) and / or liver the maximum daily dose of metronidazole is 1000 mg (the frequency of reception 2 times a day).

As a radiosensitizing drug injected intravenously drip, at a rate of 160 mg / kg or 4-6 g / m2 body surface for 0.5-1 hour 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 irradiation, a 5% solution of Dextrose, Hemodeza or 0.9% sodium chloride solution is used.

With cancer of the cervix and uterus body, skin cancer are used in the form of local applications (3 g are dissolved in 10% solution of dimethylsulfoxide), tampons are moistened, 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.

Metronidazole for intravenous fluids should not be mixed with other medications!

Side effects:

From the digestive system: nausea, vomiting, loss of appetite, intestinal colic, diarrhea, constipation, tongue lagging, bitter, "metallic" taste in the mouth. stomatitis, dry mouth, glossitis, pancreatitis.

From the hematopoietic system: reversible neutropenia (leukopenia).

From the central nervous system: peripheral neuropathy (feeling of numbness of the extremities), headaches, cramps, drowsiness, dizziness, impaired coordination of movements, ataxia, confusion, depression, increased excitability, weakness, insomnia, hallucinations, irritability.

Allergic reactions: skin rash, hives, itchy skin, erythema multiforme exudative, angioedema and anaphylactic reaction, skin hyperemia, nasal congestion, fever, arthralgia.

Local Reactions: at the site of administration, thrombophlebitis (pain, hyperemia or swelling at the injection site) is possible.

From the hepatobiliary system: increased activity of hepatic enzymes, cholestasis, jaundice.

From the genitourinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis of the vaginal mucosa, staining of urine in red-brown color (causes metronidazole metabolite, has no clinical significance).

Other: increase in body temperature, flattening of the T wave on the electrocardiogram.

Overdose:

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

Treatment: 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.

The simultaneous use of metronidazole with disulfiram can lead to the development of various neurological symptoms (the interval between appointments is at least 2 weeks).

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

Cimetidine suppresses 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 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:

Intravenous administration of a solution for infusion is indicated to patients who are unable to receive oral medication.

With mixed infections, the infusion solution of metronidazole can be used in combination with parenteral antibiotics, without mixing drugs with each other.

When intravenous drip introduction should not be mixed with other drugs.

When using the drug, there may be an exacerbation of candidiasis.

The use of alcoholic beverages during the course of therapy is strictly prohibited.

When using the drug, minor leukopenia can be observed, so it is advisable to monitor the blood picture (the number of white blood cells) at the beginning and at the end of therapy.

In combination with amoxicillin it is not recommended to use in patients younger than 18 years.

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.

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.

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

When carrying out therapy for more than 10 days - only in justified cases, with strict supervision of the patient and regular monitoring of laboratory blood counts. If a longer course of therapy is required due to the presence of chronic diseases, the relationship between the expected effect and the potential risk of complications should be carefully weighed.

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

When there are side effects from the central nervous system should refrain from driving and working with potentially dangerous mechanisms.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

100 ml in bottles of high-density polyethylene of low density.On a polyethylene bottle stick the label-parcel of paper label or label self-adhesive.

1 bottle together with the instruction for use is placed in a bag of polyethylene film, and it is welded (holes in the welded seam for the release of air from the polyethylene bag are allowed).

36 or 40 bottles in bags are placed in a box of corrugated cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of 0 to 30 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 of the year.

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

Terms of leave from pharmacies:On prescription

Registration number:P N002063 / 02

Date of registration:31.07.2008 / 11.03.2010

Expiration Date:Unlimited

The owner of the registration certificate:MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC MOSHIMFARM PREPARATES them. N.А.Semashko, OJSC Russia

Manufacturer: & nbsp

MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Representation: & nbspMOSHIMFARM PREPARATES them. NA Semashko OJSC MOSHIMFARM PREPARATES them. NA Semashko OJSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)