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

Active substance:
Metronidazole	5.0 mg
Excipients:
Sodium chloride	8.0 mg
Citric acid monohydrate	0.44 mg
Sodium hydrophosphate dodecahydrate	1.8 mg
Water for injections	up to 1 ml

Description:

Transparent, colorless or greenish-yellow solution.

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 of metronidazole 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 exhibits high activity with respect to Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as in respect of obligate anaerobes (sporo- and non-spore forming) Bacteroides spp. (AT. fragilis. AT. ovatus, AT. distasonis, AT. thetaiotaomicron, AT. vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains Eubacterium.

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 anaerobes.

Pharmacokinetics:

Distribution: the drug 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 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%.

With the intravenous administration of 500 mg of metronidazole for 20 minutes to patients with anaerobic infection, the concentration of the drug in the blood serum was 35.2 μg / ml in an hour, 33.9 μg / ml in 4 hours, 25.7 μg / ml after 8 hours . With normal bile formation, the concentration Metronidazole in bile after intravenous administration may significantly exceed the concentration of metronidazole in blood plasma.

Metabolism: 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 action

Excretion: 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 h, 36-40 weeks - 25 h. It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%. The renal clearance is 10.2 ml / min. In patients with impaired renal function after repeated administration of the drug cumulation of metronidazole in 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 amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomoniasis urethritis).
infections caused by Bacteroides spp. (including V. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus): infections of bones and joints, central nervous system (CNS) infections, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis.
infections caused by species Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (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 history), liver failure (in the case of high doses), I trimester of pregnancy; lactation period.

Carefully:

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

Pregnancy and lactation:

Metronidazole penetrates the placenta, so do not prescribe the drug in the first trimester of pregnancy, then should be used only if the potential benefit of using the drug for the mother exceeds the possible risk to the fetus.

Because the metronidazole penetrates into breast milk, reaching in it the 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.

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 is administered 7.5 mg / kg body weight in 3 divided doses at a rate of 5 ml per minute.

For the prevention of anaerobic infection before the planned operation on the pelvic organs and urinary tract adults and children over 12 years Metronidazole is administered in the form of infusions in a dose of 500-1000 mg, on the day of surgery 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 (QC (clearance of creatinine) less than 30 ml / min) and / or liver daily dose of metronidazole is 1000 mg, the frequency of administration 2 times a day. Metronidazole, solution for infusions, it is not recommended to mix with other medicinal products!

Side effects:

Very Frequent -> 10%; frequent -> 1% and <10%; infrequent -> 0.1% and <1%; rare -> 0.01% and <0.1%; very rare - <0.01%.

From the digestive system: rarely - epigastric pain, nausea, vomiting, diarrhea, constipation, intestinal colic, decreased appetite, anorexia, a taste disorder, an unpleasant "metallic" taste in the mouth, dryness of the oral mucosa, glossitis, stomatitis; very rarely - a deviation from the norm of the results of tests for the functional state of the liver, cholestatic hepatitis, jaundice, pancreatitis;

From the central nervous system: with prolonged use very rarely - headache, dizziness, impaired coordination of movements,ataxia, peripheral neuropathy, increased excitability, irritability, depression, sleep disturbance, drowsiness, weakness, confusion, hallucinations, seizures, encephalopathy;

From the genitourinary system: very rarely - a burning sensation in the urethra, vulvovaginal candidiasis, dysuria, cystitis, polyuria, urinary incontinence, pain in the vagina, staining the urine in a red-brown color.

Allergic reactions: very rarely - skin rash, itching, urticaria, exudative erythema multiforme, congestion, fever;

From the side of the musculoskeletal system: very rarely - arthralgia, myalgia;

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

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

Other: flattening of the T wave on the electrocardiogram (ECG); very rarely - ototoxicity, pustular eruptions, gynecomastia.

Overdose:

Symptoms: nausea, vomiting, dizziness, in more severe cases - ataxia, paresthesia and seizures.

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

Interaction:

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 in the last two weeks. Similarly, disulfiram causes intolerance to ethanol.

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 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.

Lithium. 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.

The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.

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

Metronidazole reduces ground 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:

With caution appoint for diseases of the kidneys, liver.

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 polyethylene bottles without a cap or with a welded Euro cap or plastic cap or infusion plug.

For 1 bottle in a sealed bag of polymer film or without a package in a pack of cardboard box together with instructions for use, or without a pack (for hospitals).

From 1 to 96 bottles without packs in hermetically sealed bags or without packages with an equal number of instructions for use in a corrugated box (for hospitals).

Storage conditions:

In a dry, dark place at a temperature of 2 to 30 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001517

Date of registration:16.02.2012 / 17.11.2015

Expiration Date:16.02.2017

The owner of the registration certificate:EAST-PHARM, LLCEAST-PHARM, LLC

Manufacturer: & nbsp

EAST-PHARM, LLC

Representation: & nbspEAST-PHARM, LLCEAST-PHARM, LLC

Information update date: & nbsp10.09.2016

Illustrated instructions

Instructions

Metronidazole (Metronidazole)