Metronidal - 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 reacts with the deoxyribonucleic cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Metronidal® is active against:

- protozoa: Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Lamblia spp .;

- anaerobic bacteria: Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Clostridium spp., Eubacterium spp., Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp.), Prevotella spp. (in t.h. Prevotella bivia, Prevotella buccae, Prevotella disiens), Veillonella spp .;

- facultative anaerobes: Gardnerella vaginalis Helicobacter pylori, Campylobacter spp., including Campylobacter jejuni.

The range of the minimum inhibitory concentrations for these strains is 0.125-6.25 μg / ml.

Metronidazole in combination with amoxicillin is active 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), 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 barrier and placental barrier.

The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg. The maximum concentration is from 6 to 40 μg / ml depending on the dose. The time to reach the maximum concentration is 1-3 hours. The connection with plasma proteins is 10-20%.

When intravenously administered 500 mg for 20 minutes, the maximum serum concentration in 1 hour is 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8-25.7 μg / ml; the minimum concentration for subsequent administration is 18 μg / ml.The time to reach the maximum concentration is 30-60 minutes, the therapeutic concentration is maintained 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 alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns: those born at the time of pregnancy - 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 (the elimination half-life is reduced to 2.6 h).When peritoneal dialysis is withdrawn in small quantities.

Indications:

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

- infections caused by anaerobic microorganisms:

- infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection bones and joints, infection central nervous system, incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess;

- infections caused by species Bacteroides, including group Bacteroides fragilis, as well as Clostridium, Eubacterium, Peptococcus and Peptostreptococcus: infection of the abdominal cavity (peritonitis, intra-abdominal abscess, liver abscess), pelvic infection (endometritis, endomyometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection after surgery, pelvic abscess), skin and soft tissue infections (including postoperative wounds);

- infections caused by species Bacteroides, including group Bacteroides fragilis and species Clostridium: sepsis;

- prevention of postoperative infectious complications (especially with interventions on the colon and rectum, near-rectal area,with gynecological operations and organs of the abdominal cavity, with appendectomy), performed before the operation, intraoperatively and after surgery;

- Radiation therapy of patients with tumors - as a radiosensitizing agent, in cases when tumor resistance is caused by hypoxia in tumor cells.

Contraindications:

Hypersensitivity to metronidazole and other derivatives of 5-nitroimidazoles, leukopenia (including in the anamnesis), organic lesions of the central nervous system (including epilepsy), hepatic insufficiency (in case of appointment of large doses), pregnancy (I trimester), lactation period.

Carefully:

Pregnancy (II-III trimesters), renal / hepatic insufficiency.

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

Dosing and Administration:

Intravenously adults and children over 12 years of age: in an initial dose of 0.5-1 g (duration infusion - 30-60 minutes), and then every 8 hours 0.5 g each at a rate of 5 ml / min. The course of treatment is 7 days, but if necessary, intravenous administration is continued for a longer time. The maximum daily dose is 4 g.With the improvement of the patient's condition, according to the indications, the patient passes to the maintenance dose inside at a dose of 0.4-0.5 g 3-4 times / day.

Children under 12 years: metronidazole prescribe the same scheme in a single dose 7.5 mg / kg (30-40 min) every 8 hours.

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

For the prevention of postoperative infectious complications adults and children over 12 years of age are prescribed intravenously drip at a dose of 15 mg / kg (approximately 1 g to a patient with a body weight of 70 kg) 1 hour before the start of the operation (duration of infusion is 30-60 minutes), then repeat intravenous drip of metronidazole in a dose 7.5 mg / kg (approximately 0.5 g to a patient with a body weight of 70 kg) every 6 hours after the first administration of the drug. 1-2 days after the operation (when it is already allowed to enter) - go to metronidazole inward at a single dose of 7.5 mg / kg (approximately 0.5 g to a patient with a body weight of 70 kg) every 6-8 hours for 7 days.

Patients with chronic renal insufficiency and with creatinine clearance 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 radiosensitizing the drug is injected intravenously at the rate of 160 mg / kg or 4-6 g / m2 body surface for 0.5-1.0 h before the start of irradiation. Apply before each irradiation session for 1-2 weeks. Metronidal® is not used in the remaining period of radiotherapy. The maximum single dose should not exceed 10 g, the course - 60 g. To remove intoxication caused by irradiation, use a drip introduction 5% solution of dextrose, haemodesis or 0.9% solution of sodium chloride.

With cancer of the cervix, skin cancer 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, 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 urinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color.

Local reactions: thrombophlebitis (pain, redness or swelling in place injections).

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

Overdose:

Specific symptoms of an overdose are absent.

Treatment - The specific antidote is unknown. Therapy of an overdose consists of hemodilution, maintenance and symptomatic therapy. In severe cases, hemodialysis is used.

Interaction:

Metronidazole for intravenous administration is not recommended to be mixed with other medicines!

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.

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 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 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.

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

Packaging:

100 ml of the drug in bottles or bottles of glass with a capacity of 100 ml.

1 A bottle or bottle with instructions for use is placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children. Do not freeze.

Shelf life:

2 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-009319/08

Date of registration:25.11.2008 / 07.02.2018

Expiration Date:Unlimited

The owner of the registration certificate:PREBAND PFC, LLCPREBAND PFC, LLC Russia

Manufacturer: & nbsp

PREBAND PFC LLC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidal® (Metronidal®)