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

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 deoxyribonucleic acid of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active in a relationship Trichomonas vaginalis, Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. AT. fragilis, B.distasonis, AT. ovatus, B. thetaiotaomicron, V. vulgatus), Fusobacterium spp. and some Gram-positive anaerobes (sensitive strains Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). The minimum inhibitory concentration for these strains is 0.125-6.25 μg / ml.

In combination with amoxicillin shows activity against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

Metronidazole is insensitive 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.

Increases the sensitivity of tumors to radiation, causes sensitization to alcohol (disulfiram-like action).

Pharmacokinetics:

Absorption is high (bioavailability is not less than 80%). It 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 the blood-brain and placental barriers. The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg.

The maximum concentration of the drug in the blood is from 6 to 40 μg / ml, depending on the dose. The time to reach the maximum concentration is 1-3 hours. The connection with plasma proteins is 10-20%.

In the body it is metabolized by 30-60% Metronidazole by hydroxylation, oxidation and glucuronation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

Half-life with normal liver function is 8 hours (6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns: those born at the gestational age - 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, cumulation of metronidazole in serum can be observed (therefore, the frequency of admission should be reduced in patients with severe renal insufficiency).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (the elimination half-life is reduced to 2.6 h). When peritoneal dialysis is withdrawn in small quantities.

Indications:

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

- Infections caused by Bacteroides spp. (incl. V. fragilis, B.Distasonis, B. ovatus, B. thetaiotaomicron, V. vulgatus): infections of bones and joints, infections of the central nervous system (CNS), incl. 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), pelvic infection (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection).

- Pseudomembranous colitis (associated with the use of antibiotics).

- Gastritis or duodenal ulcer associated with Helicobacter pylori.

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

Contraindications:

Increased individual sensitivity to the drug, leukopenia (including in the anamnesis), organic damage to the central nervous system (including epilepsy), liver failure (in the case of high doses), children under 3 years (for this drug forms).

Carefully:Pacute / hepatic insufficiency, liver disease, alcoholism.

Pregnancy and lactation:

The use of the drug during pregnancy is contraindicated.

During lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, during or after a meal (or squeezed milk), without chewing.

With amebiasis, adults - 750 mg 3 times a day for 5-10 days; with amoebic liver abscess - 500-750 mg 3 times a day for 10 days; children with amoebiasis - 35-50 mg / kg / day in 3 divided doses for 10 days.

With trichomoniasis - once 2000 mg per day in one or two doses or in the form of course therapy - 250 mg 3 times a day for 7 days. If necessary, you can repeat the course of treatment after 4-6 weeks. with the conduct of repeated control laboratory tests. To avoid possible reinfection, it is necessary to simultaneously treat the sexual partner.

Anaerobic bacterial infections - 7.5 mg / kg every 6 hours (approximately 500 mg for an adult with a body weight of 70 kg), usually for 7-10 days, however, infections of bones and joints, lower respiratory tract and endocarditis may require longer treatment. The maximum daily dose is 4000 mg.

With pseudomembranous colitis - 500 mg 3-4 times a day.

For eradication of Helicobacter pylori - 500 mg 3 times a day for 7 days (as part of combination therapy, for example, combination with amoxicillin 2250 mg / day).

For the prevention of postoperative infectious complications - 750-1500 mg / day in 3 doses 3-4 days before surgery or once 1000 mg on the first day after the operation. In 1-2 days after the operation (when already allowed ingestion) - 750 mg / day for 7 days.

With severe renal dysfunction (creatinine clearance less than 10 ml / min) daily dose should be reduced by 2 times.

Side effects:

From the digestive system: pain in epigastrium, diarrhea, loss of appetite, nausea, vomiting, intestinal colic, constipation, "metallic" taste in the mouth, dryness of the oral mucosa, glossitis, stomatitis, pancreatitis.

From the nervous system: dysarthria, encephalopathy, aseptic meningitis, optic nerve neuropathy, dizziness, movement coordination disorders, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy.

Allergic reactions: malignant exudative erythema (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), urticaria, skin rash, skin hyperemia, nasal congestion, fever, arthralgia.

From the urinary system: dysuria, cystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color.

Other: neutropenia, leukopenia, flattening of the T wave on the electrocardiogram, candidiasis of the vagina, reversible thrombocytopenia, decreased libido.

Overdose:

Symptoms: nausea, vomiting, ataxia, in severe cases - peripheral neuropathy and epileptic seizures.

Treatment: symptomatic; there is no specific antidote.

Interaction:

Increases the effect of indirect anticoagulants, which leads to an increase in prothrombin time.

Similarly, disulfiram causes intolerance to ethanol. Simultaneous use with disulfiram can lead to the development of various neurologic symptoms (the interval between appointments is at least 2 weeks).

Cimetidine suppresses 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.

With simultaneous administration with lithium preparations, the concentration of the latter in the plasma and the development of symptoms of intoxication may increase.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

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).

In combination with amoxicillin it is not recommended to use in patients younger than 18 years. 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.

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. Treatment does not stop during menstruation. After trichomoniasis therapy, control tests should be performed for three consecutive cycles before and after menstruation.

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

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

Form release / dosage:

Tablets, 250 mg.

Packaging:

For 10 tablets in a contour non-cellular package of paper with a polymer coating or paper with a polyethylene coating, or in a contour mesh box made of a polyvinylchloride film and foil of aluminum printed lacquered.

For 2 or 5 contour squares, together with the instructions for use, are placed in a pack of cardboard.

Contour non-cellular packages, together with an equal number of instructions for use, are placed in a group package (for hospitals).

For 20 or 50 tablets in cans of polymeric.

Each bank along with the instruction for use is placed in a pack of cardboard.

Storage conditions:

In a dry, dark place at a temperature of 2 to 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N003914 / 01

Date of registration:16.11.2009 / 24.10.2013

Expiration Date:Unlimited

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Representation: & nbspDALHIMFARM, OJSCDALHIMFARM, OJSC

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)