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

Antimicrobial and antiprotozoal 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 DNA 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 obligate anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Prevotella (P. bivia, P. buccae, P. disiens) and some, Gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The minimum inhibitory concentration for these strains is 0.125-6.250 μg / ml.

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

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:

Absorption is high (bioavailability is not less than 80%). It has a high penetrating power, 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.

Distribution: adults - approximately 0.55 l / kg. The maximum concentration of the drug in the blood (C_mOh) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration (TC_mOh) - 1-3 hours. Connection with plasma proteins -10-20%.

The body metabolizes about 30-60% Metronidazole by hydroxylation, oxidation and glucuronation. The main metabolite (2-oxymetronidazole) also has an antimicrobial and antiprotozoal effect.

The half-life (T_1/2) with normal liver function - 8 hours (6 to 12 hours), with alcohol damage of the liver - 18 hours (10 to 29 hours), Kidney 60-80% (20% unchanged), intestine 6-15% .

Renal 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 (T_1/2 is reduced to 2 hours). When peritoneal dialysis is withdrawn in small quantities.

Indications:

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

Infections caused by Bacteroides spp. (incl. AT. fragilis, AT. distasonis, AT. ovatus, AT. thetaiotaomicron, AT. vulgatus): infections of bones and joints, infection of the central the nervous system (CNS), incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess.

Infections caused by the species Clostridiums spp., Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (endometritis, endomyometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection after surgical operations).

Infections caused by the species Bacteroides, including a group AT. fragilis and species Clostridium: sepsis.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori (as part of complex therapy).

Prevention of postoperative complications (especially interference on the colon, near the rectal region, apendectomy, gynecological operations).

Contraindications:

Hypersensitivity to metronidazole, other imidazoles, the derivative of nitroimidazole, other components of the drug, leukopenia (including in the anamnesis), organic lesions of the central nervous system (including epilepsy), liver failure (in the case of high doses), pregnancy, the period of breastfeeding, children under 3 years.

Carefully:

With renal and / or liver failure.

Pregnancy and lactation:

The use of the drug during pregnancy and during breastfeeding is contraindicated.

If you need to use the drug during breastfeeding, breastfeeding should be discarded.

Dosing and Administration:

Inside, before or after eating, with plenty of water.

With intestinal amebiasis adults are prescribed 1500 mg per day for three doses for 7 days. In acute amoebic dysentery - The daily dose is 2,250 mg divided into three doses until the symptoms disappear. Children from 3 to 15 years - 500 mg per day for two meals. The duration of treatment is determined by the doctor.

With abscess of the liver and other extraintestinal forms of amoebiasis the maximum daily dose for adults is 2500 mg, divided into 3 doses for 3-5 days, in combination with tetracycline antibiotics and other therapies. Children from 3 to 15 years - 500 mg per day for two meals.

With trichomoniasis in women (urethritis and vaginitis) metronidazole appoint once in a dose of 2 g or in the form of course treatment for 10 days: 1 tablet (250 mg) 2 times a day. Women need to be additionally appointed metronidazole in the form of vaginal suppositories or tablets.

With trichomoniasis in men (urethritis) metronidazole appoint a single dose in a dose of 2 g or as a course of treatment for 1 tablet (250 mg) 2 times a day. Children 3-5 years - 250 mg per day; 5-10 years - 250-375 mg per day, over 10 years - 500 mg per day. The daily dose should be divided into 2 divided doses. The course of treatment is 10 days.

In the treatment of anaerobic infections (meningitis, endocarditis and others) the drug is prescribed in the form of stepwise therapy with switching to tablets after intravenous administration of the corresponding dosage form of metronidazole. For adults, the dose of the drug is 500 mg 3 times a day. The duration of treatment is up to 7 days. Children are prescribed 7 mg / kg every 8 hours. The course of treatment is 7-10 days.

For the treatment of pseudomembranous colitis adults are prescribed 500 mg of the drug (2 tablets) 3-4 times a day. The duration of treatment is determined by the doctor.

For eradication Helicobacter pylori adults are prescribed 500 mg of the drug 3 times a day as part of a combination therapy.

For the prevention of postoperative complications adults are prescribed 750-1500 mg per day in 3 divided doses 3-4 days before the operation. In 1-2 days after the operation (when ingestion is already allowed) - 750 mg of the drug per day for 7 days.

Side effects:

From the digestive system: diarrhea, anorexia, nausea, vomiting, intestinal colic, constipation, "metallic" taste in the mouth, dryness of the oral mucosa, glossitis, stomatitis, pancreatitis, impaired liver function, cholestatic hepatitis, jaundice.

From the nervous system: dizziness,impaired coordination of movements, ataxia, confusion, irritability, depression, increased excitability, weakness, insomnia, headache, convulsions, hallucinations, peripheral neuropathy, dysarthria, nystagmus, tremor, aseptic meningitis.

From the sense organs: diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception, optic neuritis.

Allergic reactions: urticaria, skin rash, itching, skin hyperemia, nasal congestion, fever, arthralgia, angioedema, anaphylactic shock.

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

Other: neutropenia, leukopenia, agranulocytosis, thrombocytopenia, flattening of the T wave on the electrocardiogram.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

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

Treatment: symptomatic; there are no specific antidotes.

Interaction:

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

Similarly to 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 inhibits metronidazole metabolism, which can lead to an increase in its serum concentration 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, as a result of which its concentration in the plasma decreases.

Together with the admission lithium drugs may increase the plasma concentration of the latter and the development of symptoms of intoxication.

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

Sulfonamides increase the antimicrobial effect of metronidazole.

With the simultaneous administration of metronidazole with cyclosporine, the serum concentration of cyclosporine can increase.If simultaneous use of these two metronidazoles is required, monitoring of the serum concentration of cyclosporine and creatinine is required.

Metronidazole reduces the clearance of fluorouracil, leading to an increase in its toxicity.

Metronidazole increases the concentration of busulfan in the blood plasma, which can lead to the development of severe toxic effects of busulfan.

Special instructions:

During the period of treatment, ethanol intake is contraindicated (a disulfiram-like reaction may develop: spastic abdominal pain, nausea, vomiting, headache, sudden "tide" of blood to the face).

In combination with amoxicillin is not recommended for 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 worsening of 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 trichomonas vaginitis in women and trichomoniasis, men should refrain fromsex life. 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.

If it is necessary to simultaneously use metronidazole and indirect anticoagulants, prothrombin time should be carefully monitored and the anticoagulant dose should be adjusted.

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

In connection with the possibility of dizziness and other side effects associated with taking the drug, it is recommended to refrain from driving, servicing moving mechanisms and practicing other potentially hazardous activities requiring increased attention.

Form release / dosage:

Tablets, 250 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

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

Storage conditions:

In a dry, 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002616

Date of registration:22.03.2012

Expiration Date:Unlimited

The owner of the registration certificate:KIROVSKAYA PHARMACEUTICAL COMPANY, LTD. KIROVSKAYA PHARMACEUTICAL COMPANY, LTD. Russia

Manufacturer: & nbsp

KIROVSKAYA PHARMACEUTICAL COMPANY, LTD. Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole (Metronidazole)