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

Active substance:
Metronidazole	- 5 mg
Excipients:
Sodium chloride	- 8 mg
Sodium hydrophosphate dodecahydrate (sodium phosphate disubstituted 12-water)	- 0.6 mg
Sodium dihydrogen phosphate (sodium phosphate monosubstituted)	- 0.45 mg
1M hydrochloric acid solution	- to pH 4.5-6.0
Water for injections	- up to 1 ml
Theoretical osmolality	- 286.3 mOsm / l

Description:

Transparent, colorless or light yellow with a greenish tinge of liquid.

Pharmacotherapeutic group:Antimicrobial and antiprotozoal drug

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Metronidazole is an antiprotozoal and antibacterial agent of a wide spectrum of action.

Active with respect to Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. B.fragilis, B.distasonis, B.ovatus, B.thetaiotaomicron, B.vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.).

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.

Pharmacokinetics:

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 .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. Binding to blood proteins is weak and does not exceed 10-20%. With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

Metronidazole is excreted by the kidneys - 63% of the dose, 20% of the drug is excreted unchanged. The half-life of metronidazole is 6-7 hours. 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.

Indications:

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

Infections caused by Bacteroides spp. (including AT. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus): infections of bones and joints, infections of the central nervous system, including 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).

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);

- hepatic insufficiency (in case of application of large doses);

- leukopenia (including in the anamnesis);

- I trimester of pregnancy,

- lactation period.

Carefully:

With caution appoint for diseases of the kidneys, liver (renal / hepatic insufficiency).

II and III trimesters of pregnancy - only for life indications.

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 infuzionalno.

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 daily dose of metronidazole 1000 mg; (the frequency of reception 2 times).

Side effects:

Disorders from the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, metallic taste in the mouth, decreased appetite, anorexia, dryness of the oral mucosa, constipation, pancreatitis (reversible cases), discoloration of the tongue / "lipped tongue" ( because of the growth of fungal microflora).

Immune system disorders: angioedema, anaphylactic shock.

Disturbances from the nervous system: peripheral sensory neuropathy, headache,convulsions, dizziness, reported on the development of encephalopathy and subacute cerebellar syndrome (disruption of coordination and synergy movement, ataxia, dysarthria, gait disorders, nystagmus, tremor), which are reversible after the withdrawal of metronidazole, aseptic meningitis.

Disorders of the psyche: psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

Disturbances on the part of the organ of sight: transient visual impairment, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

Violations of the blood and lymphatic system: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Disturbances from the liver and bile ducts: increase in the activity of "hepatic" enzymes (aspartates -notransferase, alanine aminotransferase, alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice; in patients,treated with metronidazole in combination with other antibacterial agents, there were cases of liver failure that required liver transplantation.

Disturbances from the skin and subcutaneous tissues: rash, itching, skin hyperemia, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disorders from the kidneys and urinary tract: staining urine in a brownish-reddish color due to the presence in the urine of a water-soluble metronidazole metabolite, dysuria, polyuria, cystitis, urinary incontinence, candidiasis.

General disorders and disorders at the site of administration: fever, nasal congestion, arthralgia, weakness, thrombophlebitis (pain, flushing or swelling at the injection site).

Laboratory and instrumental data: flattening of the T wave on the electrocardiogram.

Overdose:

Symptoms: nausea, vomiting, ataxia, dizziness, headache. In severe acute overdose of metronidazole - seizures, peripheral neuropathy and epileptic seizures.

Treatment: there is no specific antidote.Therapy of an overdose consists of hemodilution, maintenance and symptomatic therapy. In severe cases, hemodialysis is used.

Interaction:

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

When metronidazole is used for injections, interaction with other drugs is negligible, but caution should be exercised when using several medicines at the same time.

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

Disulfiram. 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.

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 use of drugs that stimulate enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, resulting in reduced its concentration in the plasma.

In patients receiving long-term treatment with drugs lithium in high doses, the use of metronidazole may increase the concentration of lithium in blood plasma and the development of symptoms of intoxication.

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

With the combined use 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).

Metronidazole is incompatible with ethanol (when combined use develops disulfiropodobnye reaction).

Special instructions:

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

In / in the introduction of a solution for infusions is indicated for patients in whom oral administration of the drug is not possible.With mixed infections, the infusion solution of metronidazole can be used in combination with parenteral antibiotics, without mixing drugs with each other.

When i / v drip introduction can not be mixed with other drugs. When using the drug, there may be an exacerbation of candidiasis.

Drinking alcohol during the course of therapy is strictly prohibited (it is possible to develop a disulfiram-like reaction: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).

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.

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.

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 a glass bottle, sealed with a rubber stopper and crimped with an aluminum cap.

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

For hospitals: 56 bottles with an equal number of instructions for use are placed in a group box - boxes of cardboard corrugated.

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 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002746

Date of registration:09.12.2014 / 07.11.2017

Expiration Date:09.12.2019

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Representation: & nbspBIOSINTEZ JSC BIOSINTEZ JSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)