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

Active substance:
Metronidazole	- 500 mg
Excipients:
Sodium chloride	- 790 mg
Sodium hydrophosphate dihydrate (in terms of sodium hydrophosphate)	- 47.6 mg
Citric acid anhydrous	- 20.9 mg
Water for injection	- up to 100 ml

Theoretical osmolarity - 309 mOsm / l

Description:Transparent, colorless or slightly yellow or slightly yellow in color with a greenish liquid.

Pharmacotherapeutic group:antimicrobial and antiprotozoal agent

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 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.

The drug shows a high activity in a relationship Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as in respect of obligate anaerobes (sporo- and non-spore forming) Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides about vat us. Bacteroides vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium spp. Peptococcus niger, Peptostreptococcus spp.).

To Metronidazole insensitive Aerobic microorganisms and facultative anaerobes, in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional aerobes.

Pharmacokinetics:

Metronidazole has a high penetrating ability, reaching bactericidal concentrations in most tissues and body fluids, including lungs, nights, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk; penetrates through 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%,

When intravenously administered 500 mg of metronidazole for 20 minutes, the maximum concentration (C_max) of the drug in the blood serum was after 1 h -35.2 μg / ml; after 4h-33.9 mcg / ml; after 8 hours, 25.7 μg / ml; minimum concentration (C_min) of the drug in the blood serum with subsequent administration - 18 mcg / ml. Time to reach the maximum concentration (TC_max) - 30-60 minutes, the therapeutic concentration is maintained for 6-8 hours. With normal bile formation, the concentration of metronidazole in bile after intravenous administration may significantly exceed the concentration of metronidazole in blood 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.

The 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 born at the gestation period of 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%

Kidney clearance - 10.2 ml / min.

In patients with impaired renal function after repeated administration of the drug cumulation of metronidazole in the blood serum can be observed, therefore, in patients with severe renal failure, the frequency of metronidazole should be reduced.

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:

Metronidazole is recommended for the treatment of infections caused by microorganisms that are sensitive to the drug:

protozoal infections: extraintestinal amoebiasis, including amoebic abscess, you consume intestinal amoebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis);
infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides ovatus, Bacteroides vulgatus): infection of bones and joints, infections of the central nervous system, incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis;
infections caused by species Clostridium spp., Peptococcus niger, Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), infections of small organs (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection).

Prevention of postoperative complications (especially interference on the colon, paraectal area, appendectomy, gynecological operations).

Contraindications:

Hypersensitivity to metronidazole or other nitroimidazole derivatives, organic lesions of the central nervous system (including epilepsy), leukopenia (including in the anamnesis), liver failure (in the case of high doses), I trimester of pregnancy, lactation period .

Carefully:Renal and / or hepatic insufficiency, pregnancy (II-III trimesters) - only for vital indications.

Pregnancy and lactation:

Metronidazole penetrates the placenta, so do not prescribe the drug in the first trimester of pregnancy.The use of the drug in the II-III trimesters of pregnancy is possible only if the intended use for the substance exceeds the potential risk to the fetus.

Because the metronidazole penetrates into breast milk, reaching in it concentrations close to the concentrations in the blood plasma, it is recommended to stop breastfeeding during treatment with the drug.

Dosing and Administration:

Intravenously sprayed or drip.

For adults and children over 12 years single vine is 500 mg, the rate of intravenous continuous (jet) or dropwise administration is 5 ml / min. The interval between the administrations is 8 hours. The duration of the course of treatment is determined individually. The maximum daily dose of 4 g. According to the indications, depending on the nature of the infection, a transition is made to maintenance therapy with oral forms of metronidazole.

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 / min.

For the prevention of anaerobic infection before the planned operation on the pelvic organs and urinary tract adults and children over 12 years 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.

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. The maximum daily dose in children under 12 years of age is 22.5 mg / kg body weight.

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

Side effects:

From the digestive system: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, taste disorder, "metallic" taste in the mouth, decreased appetite, anorexia, dryness of the oral mucosa. intestinal colic, constipation, pancreatitis (reversible cases), discoloration of the tongue / "coated tongue" (due to the growth of the fungal microflora), increased activity of "hepatic" enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular lesions of the liver, sometimes accompanied by jaundice; in patients,treated with metronidazole in combination with other antibacterial agents, there have been cases of liver failure that required liver transplantation.

From the central nervous system: peripheral sensory neuropathy, headache, convulsions, dizziness, drowsiness, weakness, psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability, reported on the development of encephalopathy and subacute cerebellar syndrome (impaired coordination and synergy of movements, ataxia, dysarthria, gait disorders, nystagmus, tremor) that are reversible after metronidazole withdrawal, aseptic meningitis.

From the sense organs: transient visual impairments, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

From the skin: rash, itching, skin hyperemia, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Allergic reactions: exudative erythema multiforme, fever, nasal congestion, angioedema, anaphylactic shock.

From the urinary system: staining of urine in a brownish-reddish color due to the presence in the urine of a water-soluble metabolite of metronidazole, dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

From the genitourinary system: a burning sensation in the urethra, pain in the vagina.

From the side of the musculoskeletal system: arthralgia, myalgia.

On the part of the organs of hematopoiesis: agranulocytosis, leukopenia, neutropenia, thrombocytopenia, pancytopenia.

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

Other: flattening of the T wave on the electrocardiogram, ototoxicity, pustular eruptions, gynecomastia.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: nausea, vomiting, dizziness, in more severe cases, there may be ataxia, paresthesia and seizures.

Treatment: symptomatic and supportive therapy.There is no specific antidote.

Interaction:

Metronidazole, a solution for infusions, it is not recommended to mix with other medicinal products!

Warfarin and other indirect anticoagulants. Metronidazole increases the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Disulfiram (Esperal). Simultaneous application can lead to the development of various neurological symptoms, so one should not prescribe metronidazole patients who took disulfiram during the last two pedals. Similarly, disulfiram causes intolerance to ethanol.

Cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its concentration at blood serum and 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, resulting in reduced its concentration in the plasma.

Lithium preparations. In patients who receive long-term treatment with lithium preparations in high doses, with the use of metronidazole, an increase in the concentration of lithium in the blood plasma and the development of symptoms of intoxication are possible.

Sulfonamides and antibiotics enhance the antimicrobial effect of metronidazole.

With the combined administration of metronidazole and cyclosporine there may be an increase in the concentration of cyclosporine in the blood plasma.

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

With simultaneous application metronidazole can increase plasma concentrations busulfan.

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

Special instructions:

During the treatment period, ethanol intake is contraindicated (development of disulfiram-like reactions is possible: abdominal pain of spastic nature, nausea, vomiting, headache, sudden rush of blood to the face).

Long-term use of the drug is desirable to be carried out under the control 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.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

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

Packaging:

For 100 ml in PVC containers for single-use infusion solutions with two sterile ports. Each container is placed in a bag of polyethylene or polyethylene-polyamide film (a double sterile vacuum package).

Containers in bags are placed in a box of corrugated cardboard: 50, 75, 96 pieces. Instructions for the medical use of the drug and guidance on the use of infusion solutions in polymer containers in an amount equal to the number of containers (for hospitals) are put in a container box.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

2 of the year.

To use after the expiry date stated on the package.

Terms of leave from pharmacies:For hospitals

Registration number:LP-003033

Date of registration:15.06.2015

Expiration Date:15.06.2020

The owner of the registration certificate:MEDSINTEZ FACTORY, LTD. MEDSINTEZ FACTORY, LTD. Russia

Manufacturer: & nbsp

PLANT MEDSINTEZ, LLC Russia

Information update date: & nbsp09.09.2016

Illustrated instructions

Instructions

Metronidazole (Metronidazole)