Metronidazole solution for infusion 5 mg/ml - - Catalog Production of medicines

pharmachologic effect

Metronidazole is a broad-spectrum antiprotozoal and antibacterial agent.

Active against Trichomonas vaginalis, Entamoeba histolytica, as well as gram-negative anaerobes Bacteroides spp. (including B.fragilis, B.distasonis, B.ovatus, B.thetaiotaomicron, B.vulgatus), Fusobacterium spp. and some gram-positive anaerobes (susceptible strains of Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.).

Aerobic microorganisms and facultative anaerobes are not sensitive to metronidazole, but in the presence of mixed flora (aerobes and anaerobes), metronidazole acts synergistically with antibiotics that are effective against common aerobes.

Pharmacokinetics

The drug has 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 secretions, 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 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. Renal clearance is 10.2 ml/min.

In patients with impaired renal function, after repeated administration of the drug, accumulation of metronidazole in the blood serum may be observed. Therefore, in patients with severe renal failure, the frequency of taking metronidazole should be reduced.

Indications for use

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

Infections caused by Bacteroides spp. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. 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 Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, fallopian tube and ovarian abscess, vaginal vault infections).

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

Indications

Treatment of protozoal infections: intestinal and extraintestinal amebiasis, trichomoniasis.
Infections caused by gram-negative anaerobes of the Bacteroidaceae family: brain and lung abscesses, necrotizing pneumonia, infections of the osteoarticular system, bacterial endocarditis and sepsis.
The drug is effective against clostridial flora, which causes infections of the genitourinary system and infections of the abdominal organs.
Metronidazole is used in gastroenterology for the treatment of gastritis, gastric and duodenal ulcers associated with H. pylori.
Prophylactic use during operations on the colon and gynecological interventions.

Contraindications

- hypersensitivity to metronidazole or other nitroimidazole derivatives;

— organic lesions of the central nervous system (including epilepsy);

- liver failure (in case of large doses);

— leukopenia (including history);

— I trimester of pregnancy,

- lactation period.

Carefully

Prescribe with caution for kidney and liver diseases (renal/liver failure).

II and III trimesters of pregnancy - only for health reasons.

Use during pregnancy and breastfeeding

Metronidazole should not be prescribed in the first trimester of pregnancy; in the future it should be used only if the potential benefit of the drug for the mother outweighs the possible risk to the fetus.

Since metronidazole passes into breast milk, reaching concentrations similar to those in plasma, it is recommended to stop breastfeeding during treatment with the drug.

Side effects and features of administration

The most common violations:

Gastrointestinal tract: abdominal discomfort, nausea, vomiting, impaired taste perception (“metallic” taste in the mouth), diarrhea;
immunity: anaphylactic shock, angioedema;
skin: rash, itching, urticaria;
genitourinary system: change in the color of urine up to a reddish-brown color, candidiasis.

The drug crosses the placental barrier, which completely limits its use in the first trimester of pregnancy. In the second and third trimester, metronidazole is used if the estimated risk to the fetus is lower than the possible benefit to the pregnant woman. Treatment of a lactating woman requires cessation of breastfeeding.

When treating trichomoniasis, it is necessary to carry out therapy simultaneously in both partners and to exclude sexual contact for the period of therapy.

special instructions

Long-term use of the drug should preferably be carried out under the control of peripheral blood parameters.

IV administration of a solution for infusion is indicated for patients in whom oral administration of the drug is impossible. For mixed infections, metronidazole infusion solution can be used in combination with parenteral antibiotics without mixing the drugs with each other.

When administered intravenously, it should not be mixed with other drugs. When using the drug, an exacerbation of candidiasis may occur.

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

When using the drug, slight leukopenia may occur, so it is advisable to monitor the blood picture (the number of leukocytes) 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 cessation of treatment.

May immobilize treponemes and lead to a false-positive Nelson test. When treating trichomonas vaginitis in women and trichomonas urethritis in men, it is necessary to abstain from sexual activity. Simultaneous treatment of sexual partners is mandatory. After treatment for trichomoniasis, control tests should be carried out during 3 consecutive cycles before and after menstruation.

When carrying out therapy for more than 10 days - only in justified cases, with strict monitoring of the patient and regular monitoring of laboratory blood parameters. If a longer course of therapy is necessary due to the presence of chronic diseases, the balance between the expected effect and the potential risk of complications should be carefully weighed.

Instructions for use of the drug metronidazole

Inside, with a glass of water.
The daily dose is divided into 3 doses for adults, and 2 doses for children 6-15 years old. For trichomoniasis infection, 2 treatment regimens are used: 2 g of the drug once or 0.250 g twice a day, course 10 days.

When Helicobacter pylori is irradiated, metronidazole is combined with penicillin antibacterial drugs to suppress drug resistance. The daily dose of metronidazole is 1.5 g.

Metronidazole in the treatment of intestinal amebiasis is used in a daily dose of 1.5 g.

For acute amoebiasis, the daily dose is 2.250 g. The daily dose for children is 0.5 g.

Treatment of extraintestinal forms of amebiasis requires combination with tetracycline antibacterial drugs. The daily dose of metronidazole is 2.5 g in adults and 0.5 g in children.

Prevention of complications after surgical interventions involves taking 0.750 - 1.5 g of the drug per day for 4 days before surgery and 0.750 in the postoperative period for a week.

Directions for use and doses

Intravenous infusion.

Intravenous administration of metronidazole is indicated for severe infections, as well as in the absence of the possibility of taking the drug orally.

For adults and children over 12 years of age, the single dose is 500 mg, the rate of intravenous continuous (jet) or drip administration is 5 ml per minute. The interval between injections is 8 hours. The duration of treatment is determined individually. The maximum daily dose is no more than 4 g. According to indications, depending on the nature of the infection, a transition to maintenance therapy with oral forms of metronidazole is carried out.

For children under 12 years of age, metronidazole is administered at 7.5 mg/kg body weight in 3 doses at a rate of 5 ml per minute.

To prevent anaerobic infection before planned surgery on the pelvic organs and urinary tract for adults and children over 12 years of age, metronidazole is prescribed as an infusion at 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 ocloc'k). After 1-2 days, they usually switch to maintenance therapy with oral forms of metronidazole.

For patients with severe renal impairment (creatinine clearance less than 30 ml/min) and/or liver, the daily dose of metronidazole is 1000 mg; (multiplicity of administration is 2 times).

Metronidazole solution d/inf 5mg/ml 100ml No.1

Compound

Active substance: metronidazole - 5 mg Excipients: sodium chloride - 8.0 mg, citric acid monohydrate - 0.44 mg, sodium hydrogen phosphate dodecahydrate - 1.8 mg, water for injection - up to 1 ml.

Pharmacokinetics

Distribution: the drug has 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 secretions, seminal fluid, breast milk . Penetrates the blood-brain and placental barrier.

Volume of distribution: adults - approximately 0.55 l/kg, newborns - 0.54-0.81 l/kg. Bonding with plasma proteins is 10-20%.

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

Metabolism: About 30-60% of metronidazole is metabolized in the body by hydroxylation, oxidation and glucuronidation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects

Elimination: half-life (T1/2) with normal liver function - 8 hours (from 6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns born at a gestational age of 28-30 weeks - approximately 75 hours, 32-35 weeks - 35 hours, 36-40 weeks - 25 hours. 60-80% is excreted by the kidneys (20% unchanged), through the intestines - 6-15%. Renal clearance is 10.2 ml/min. In patients with impaired renal function, after repeated administration of the drug, accumulation of metronidazole in the blood serum may be observed. Therefore, in patients with severe renal failure, the frequency of taking metronidazole should be reduced. Metronidazole and its main metabolites are quickly removed from the blood during hemodialysis (T1/2 is reduced to 2.6 hours). During peritoneal dialysis, it is excreted in small quantities.

Indications for use

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

protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis).
infections caused by Bacteroides spp. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus): infections of bones and joints, infections of the central nervous system (CNS), including meningitis, brain abscess, bacterial endocarditis, pneumonia , empyema and lung abscess, sepsis.
infections caused by Clostridium spp., Peptococcus niger and Peptostreptococcus spp.: abdominal infections (peritonitis, liver abscess), pelvic infections (endometritis, fallopian tube and ovarian abscess, vaginal vault infections).

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

Contraindications

Hypersensitivity to metronidazole or other nitroimidazole derivatives, organic lesions of the central nervous system (including epilepsy), leukopenia (including a history), liver failure (if large doses are prescribed), first trimester of pregnancy;
lactation period. Carefully:

Pregnancy (II and III trimesters) - only for health reasons, renal and/or liver failure.

Directions for use and doses

Intravenous stream or drip.

Intravenous administration of metronidazole is indicated for severe infections, as well as in the absence of the possibility of taking the drug orally.

For children under 12 years of age, metronidazole is administered at 7.5 mg/kg body weight in 3 doses at a rate of 5 ml per minute.

For children under 12 years of age, it is recommended to administer metronidazole intravenously by drip according to the same regimen 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 impairment (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. Metronidazole, solution for infusion, is not recommended to be mixed with other medications!

Storage conditions

In a dry place, protected from light, at a temperature from 2°C to 30°C.

Keep out of the reach of children.

Best before date

2 years. Do not use after the expiration date indicated on the package.

special instructions

Prescribe with caution for kidney and liver diseases.
During the treatment period, ethanol intake is contraindicated (the development of disulfiram-like reactions is possible: spastic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face).
Long-term use of the drug is preferably carried out under the control of peripheral blood parameters.
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 cessation of treatment.
May immobilize treponemes and lead to a false-positive Nelson test.

Description

Antimicrobial and antiprotozoal agent.

Dosage form

Transparent, colorless or greenish-yellow solution.

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 interacts with the DNA of microbial cells, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

The drug exhibits high activity against Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as against obligate anaerobes (spore-forming and non-spore-forming) - Bacteroides spp. (B. fragilis. B. ovatus, B. distasonis, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains of Eubacterium.

Side effects

Very common - >10%; frequent - >1% and <10%; uncommon - >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, loss of appetite, anorexia, taste disturbance, unpleasant “metallic” taste in the mouth, dry oral mucosa, glossitis, stomatitis; very rarely - abnormal results of tests for the functional state of the liver, cholestatic hepatitis, jaundice, pancreatitis;

From the central nervous system: with long-term use very rarely - headache, dizziness, incoordination, ataxia, peripheral neuropathy, increased excitability, irritability, depression, sleep disturbance, drowsiness, weakness, confusion, hallucinations, convulsions, encephalopathy;

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

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

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

From the hematopoietic organs: rarely - leukopenia, agranulocytosis, neutropenia, thrombocytopenia, pancytopenia.

Local reactions: thrombophlebitis (pain, hyperemia or swelling at the injection site).

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

Use during pregnancy and breastfeeding

Metronidazole crosses the placenta, so the drug should not be prescribed in the first trimester of pregnancy; in the future it should be used only if the potential benefit of the drug for the mother outweighs the possible risk to the fetus.

Since metronidazole passes into breast milk, reaching concentrations similar to those in plasma, it is recommended to stop breastfeeding during treatment with the drug.

Interaction

Warfarin and other indirect anticoagulants. Metronidazole enhances the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.
Disulfiram (Esperal). Concomitant use may lead to the development of various neurological symptoms, so metronidazole should not be prescribed to patients who have taken disulfiram within the last two weeks. Similar to disulfiram, it causes ethanol intolerance.
Cimetidine inhibits the metabolism of metronidazole, which may lead to an increase in its concentration in the blood serum and an increased risk of side effects.
The simultaneous administration of drugs that stimulate microsomal oxidation enzymes in the liver (phenobarbital, phenytoin) can accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.
Lithium. In patients receiving long-term treatment with lithium drugs in high doses, when taking metronidazole, the concentration of lithium in the blood plasma may increase and symptoms of intoxication may develop.
The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.
When taking metronidazole and cyclosporine in combination, an increase in the concentration of cyclosporine in the blood plasma may be observed.
Metronidazole reduces the clearance of fluorouracil, which may increase the toxicity of the latter.
When used concomitantly, metronidazole may increase plasma concentrations of busulfan.
It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide).

Overdose

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

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

Impact on the ability to drive vehicles and operate machinery

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

Side effect

Gastrointestinal disorders:

epigastric pain, nausea, vomiting, diarrhea, glossitis, stomatitis, “metallic” taste in the mouth, loss of appetite, anorexia, dry oral mucosa, constipation, pancreatitis (reversible cases), change in tongue color/“coated tongue” (from - for the growth of fungal microflora).

Immune system disorders:

angioedema, anaphylactic shock.

Nervous system disorders

: peripheral sensory neuropathy, headache, convulsions, dizziness, the development of encephalopathy and subacute cerebellar syndrome (impaired coordination and synergism of movements, ataxia, dysarthria, gait disturbances, nystagmus, tremor) has been reported, which are reversible after discontinuation of metronidazole, aseptic meningitis.

Mental disorders:

psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

Visual disorders:

transient visual impairments, such as diplopia, myopia, blurred outlines of objects, decreased visual acuity, impaired color perception; neuropathy/optic neuritis.

Blood and lymphatic system disorders

: agranulocytosis, leukopenia, neutropenia, thrombocytopenia.

Disorders of the liver and biliary tract

: increased activity of “liver” enzymes (aspartate aminotransferase, 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, cases of liver failure requiring liver transplantation have been observed.

Skin and subcutaneous tissue disorders

: rash, itching, skin flushing, urticaria, pustular skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Renal and urinary tract disorders

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

General and administration site disorders

: fever, nasal congestion, arthralgia, weakness, thrombophlebitis (pain, hyperemia or swelling at the injection site).

Laboratory and instrumental data

: flattening of the T wave on the electrocardiogram.

Interaction with other drugs

Metronidazole for intravenous infusion is not recommended to be mixed with other medications!

When using metronidazole for injection, there is little interaction with other drugs, but caution should be exercised when used simultaneously with certain drugs.

Warfarin and other indirect anticoagulants.

Metronidazole enhances the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Disulfiram.

Concomitant use may lead to the development of various neurological symptoms, so metronidazole should not be prescribed to patients who have taken disulfiram within the last two weeks.

Cimetidine

inhibits the metabolism of metronidazole, which may lead to an increase in its concentration in the blood serum and an increased risk of side effects.

Simultaneous use of drugs that stimulate microsomal oxidation enzymes in the liver ( phenobarbital, phenytoin

) may accelerate the elimination of metronidazole, resulting in a decrease in its plasma concentration.

In patients receiving long-term treatment with lithium

in high doses, when using metronidazole, it is possible to increase the concentration of lithium in the blood plasma and develop symptoms of intoxication.

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

With the combined use of metronidazole and cyclosporine

An increase in the concentration of cyclosporine in the blood plasma may be observed.

Metronidazole reduces the clearance of fluorouracil,

which may cause an increase in the toxicity of the latter.

When used concomitantly, metronidazole may increase plasma concentrations of busulfan.

It is not recommended to combine with non-depolarizing muscle relaxants (vecuronium bromide).

Metronidazole is incompatible with ethanol (disulfira-like reactions develop when used together).