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 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 with respect to Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., as well as obligate anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (P.bivia, P.buccae, P.disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The MIC 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 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.

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

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 (C_max) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentrations in the blood (TC_m_Oh) - 1-3 hours. Communication with plasma proteins - 10-20%.

With intravenous (IV) administration 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; the minimum concentration of the drug in the blood (C_min) with subsequent administration of 18 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.

Half-life T_1/2with 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 gestational age - 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 patients with impaired renal function after repeated administration of metronidazole cumulation in serum can be observed (hence patients with severe renal impairment receiving frequency to 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:

Protozoal infections: intestinal amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, giardiasis, balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomoniasis urethritis.

Infections caused by Bacteroides spp. (including W. 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, empyema and lung abscess.

Infections caused by the species Bacteroides, including group AT. fragilis, species Clostridium, Peptococcus and Peptostreptococcus: infection of the abdominal cavity (peritonitis, liver abscess), infection of the pelvic organs (endometritis, endomyometritis, abscess of the fallopian tubes and ovaries, vaginal vaginal infection after surgical operations), skin and soft tissue infections.

Infections caused by the species Bacteroides, including group AT. fragilis and species Clostridium: sepsis.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori, alcoholism.

Prevention of postoperative complications (especially interference on the colon, near the rectal region, apendectomy, 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 (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:BVariability (II-III trimesters), renal / hepatic insufficiency.

Pregnancy and lactation:During lactation it is recommended to stop breastfeeding.

Dosing and Administration:

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 / day.

Children under the age of 12 years prescribe the same scheme in a single dose of 7.5 mg / kg.

When purulent-septic diseases are usually conducted 1 course of treatment.

For preventive purposes, adults and children over 12 years of age appoint in / in a drop of 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.

Patients with chronic renal insufficiency (CRF) and creatinine clearance (CK) of less than 30 ml / min and / or liver failure the maximum daily dose - no more than 1 g, the frequency of reception - 2 times a day.

As a radiosensitizing agent 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 irradiation, dropwise injection of solutions of glucose, hemodeza or isotonic sodium chloride solution is used.

Side effects:

From the digestive system: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, "metallic" taste in the mouth, dry mouth, glossitis, stomatitis, pancreatitis.

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

Allergic reactions: urticaria, skin rash, skin hyperemia, nasal congestion, fever, arthralgia.

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

Local Reactions: thrombophlebitis (pain, redness, or swelling at the injection site).

Other: neutropenia, leukopenia, flattening of the T wave on the ECG.

Interaction:

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

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 reception with drugs Li+, 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.

Special instructions:

During the period of treatment, ethanol intake is contraindicated (a disulfiram-like reaction may develop: 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 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 worsening of 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.

After treatment of giardiasis, if symptoms persist, after 3 to 4 weeks, 3 feces should be analyzed at intervals of several days (in some successfully treated patients lactose intolerance caused by the invasion can persist for several weeks or months, recalling the symptoms of giardiasis).

Form release / dosage:Solution for infusions, 0,5%.

Packaging:For 100 ml in polymer containers.

Storage conditions:

AT protected from the light at a temperature of 5 to 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Not applicable after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N002465 / 01

Date of registration:15.07.2009 / 04.04.2013

Expiration Date:Unlimited

The owner of the registration certificate:RESTER, CJSC RESTER, CJSC Russia

Manufacturer: & nbsp

RESTER, CJSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)