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

Anti-protozoal and progivomicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group reacts with deoxyribonuclease of the microorganism cell, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active at respect Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., a also obligatory anaerobes Bacteroides spp. (in t.ch. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (P.bivia, P.buccae, P.disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.).

Metronidazole is not sensitive to aerobic microorganisms and facultative anaerobes.

Pharmacokinetics:

When intravenously administered 500 mg for 20 minutes, the maximum concentration of the drug (FROM_max) in serum, after 1 hour is 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml; FROM_min with subsequent administration of 18 μg / ml. Metronidazole has a high penetrating ability, reaching bactericidal concentrations in most tissues and body fluids,including the lungs, kidneys, liver, skin, spinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk, penetrates the blood-brain and placental barriers. In normal bile concentration of metronidazole in bile after i / v injection can significantly exceed the concentration in the blood plasma. Metronidazole has a high bioavailability (about 80%). Binding to plasma proteins is 10-20%.

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.

It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%. The half-life (T_1/2) is 8 hours.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to metronidazole:

- protozoal infections: extraintestinal amebiasis, including amebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (Trichomonas including Trichomonas vaginitis and urethritis);

- infection, called Bacteroides spp. (in t.h. Bacteroides fragilis, Bacteroides distasonis, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection of bones and joints, infections of the central nervous system, in t.h. meningitis, brain abscess, pneumonia, empyema and lung abscess, sepsis;

- infections caused by species Clostridium spp., Peptococcus and Peptostreptococcus: 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, pararectal area, appendectomy, gynecological operations).

Contraindications:

- Hypersensitivity to metronidazole or other 5-nitroimidazole derivatives;

- leukopenia (including in the anamnesis);

- organic lesions of the central and peripheral nervous system (including epilepsy):

- hepatic failure (in the case of the appointment of large doses);

- Pregnancy I trimester and lactation.

Carefully:

- Diseases of the kidneys, liver (renal liver failure);

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

- acute and chronic diseases of the peripheral and central nervous system (risk of weighting of neurological symptoms).

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:

The rate of intravenous or drip administration of the drug is 5 ml per minute. Intravenous administration of megonidazole is indicated in severe infections and in the absence of oral administration. According to the indications, a transition is made to the supporting oral administration.

Infections caused by anaerobic microorganisms

Adults and children over 12 years of age:

The initial dose is 1.5-2 g per day (respectively 300-400 ml of solution). As a maintenance dose every 12 hours (in special cases every 8 hours) use 0.5 g (100 ml solution, respectively), i.e. 2-3 times a day for 100 ml of solution.

Children under 12 years old:

The initial dose is 7.5 mg / kg every 8 hours for 3 days. Then in the same dose every 12 hours.

To prevent postoperative complications

Adults and children over 12 years of age:

Apply iv drip 0.5-1 g per day of operation (the drug must be discontinued 1-2 hours before the operation) and the next day - 1.5 g / day (0.5 g every 8 hours) .

Children under 12 years old:

The scheme of administration of the drug is the same as above, but a single intravenous dose is 7.5 mg / kg.

Application in terminal renal failure, impaired liver function and bile duct obstruction: with chronic renal failure and creatinine clearance less than 30 ml / min and / or liver failure, the maximum daily dose - no more than 1 g, the frequency of administration - 2 times a day.

Use in patients on hemodialysis: metronidazole and its metabolites are well excreted in hemodialysis. Since during hemodialysis, the elimination half-life decreases dramatically (up to about 3 hours), in some cases, additional administration of the drug may be necessary.

Application in elderly patients: in elderly patients, the pharmacokinetics of metronidazole may change, so it may be necessary to monitor the concentration of metronidazole in the blood serum.

Severe infection requires 5-7 days of treatment, with an uncomplicated infection in general, it takes 3-5 days. The duration of therapy can be increased at the discretion of the doctor, but the course of treatment should not exceed 10 days. This period can be extended only in isolated cases for particularly stringent indications. If possible, you should avoid repeating the therapy with metronidazole.

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, "coated tongue" (from for proliferation of fungal microflora).

Immune system disorders:

Angioedema, anaphylactic shock.

Impaired nervous system:

Peripheral sensory neuropathy, headache, convulsions, dizziness, was reported on the development of encephalopathy and subacute cerebellar syndrome (impaired coordination and synergy of movements, 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 impairments, such as: diplopia, myopia, vagueness of contours of objects, 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:

Increased activity of "hepatic" 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 hepatic insufficiency that required liver transplantation were observed.

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 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.

General disorders and disorders at the site of administration:

Fever, nasal congestion, arthralgia, weakness (for oral and parenteral dosage forms), thrombophlebitis (pain, hyperemia and swelling at the injection site) (for parenteral dosage forms).

Laboratory and instrumental data:

Compaction of the T wave on the electrocardiogram.

Overdose:

Symptoms: convulsions, peripheral neuropathy, nausea, vomiting, impaired coordination of motion.

Treatment: withdrawal of the drug, symptomatic treatment. There is no specific antidote. Metronidazole is removed by hemodialysis.

Interaction:

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

Indirect Coagulants. Metronidazole increases the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation. It is recommended to monitor prothrombin time and MNO; if necessary, reduce the dose of indirect coagulants.

Similarly to disulfiram, causes intolerance to ethanol.

Disulfiram. Simultaneous use with disulfiram can lead to the development of various neurological symptoms. Metronidazole can be used 2 weeks after taking disulfiram.

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 blood plasma decreases.

Lithium. With simultaneous reception with lithium preparations, the concentration of the latter in plasma and the development of symptoms of intoxication may increase, therefore, before starting metronidazole, it is necessary to reduce the dose of lithium or stop taking it for the duration of treatment.

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

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

When applying simultaneously metronidazole can increase plasma concentrations busulfan.

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

Special instructions:

During the period of treatment, drinking is contraindicated. possibly the development of a disulfiram-like reaction: spasmodic abdominal pain, nausea, vomiting, headache, sudden rush of blood to the face. This is due to a violation of the oxidation of ethanol and the accumulation of acetaldehyde. 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.

Carrying out therapy for more than 10 days - only in justified cases, with strict observation 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:Given the side effects of the drug, care must be taken when managing transport and working with mechanisms that require concentration.

Form release / dosage:Solution for infusions, 0,5%.

Packaging:

For 100 ml of the drug in polypropylene bottles with a holder loop, sealed with polypropylene lids with a rubber lining and equipped with a cap with a tear-off ring for opening, welded onto the vial.

One bottle, along with instructions for medical use in consumer packaging (a pack of cardboard).

For hospitals

120 vials of 100 ml, together with an equal number of instructions for medical use, are placed in a group package (carton box).

Storage conditions:

Store in a 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-003894

Date of registration:10.10.2016

Expiration Date:10.10.2021

The owner of the registration certificate:Kelun-Kazfarm, TOOKelun-Kazfarm, TOO The Republic of Kazakhstan

Manufacturer: & nbsp

Kelun-Kazpharm, TOO The Republic of Kazakhstan

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)