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

Antiprotozoal and antibacterial 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 the deoxyribonucleic acid (DNA) of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Has a wide range of action. Active with respect to protozoa - Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as Gram-negative anaerobes Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides 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 0.125-6.250 μg / ml.

In combination with amoxicillin shows activity against Helicobacter pylori.

To Metronidazole aerobic microorganisms and facultative anaerobes are not sensitive, 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 irradiation, causes disulfiram-like reactions.

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 (FROM_mOh) is from 6 to 40 μg / ml, depending on the dose. Time to reach the maximum concentration (TFROM_mOh) - 1-3 hours. Communication with plasma proteins - 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.

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).

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 of metronidazole cumulation in serum can be observed (hence patients with severe renal impairment receiving frequency to be reduced by half).

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T_1/2is reduced to 2.6 hours). When peritoneal dialysis is withdrawn in small quantities.

Indications:

- Protozoal infections: extra-intestinal amebiasis, including amebic liver abscess, intestinal amebiasis (amebic dysentery), trichomoniasis (including Trichomonas vaginitis, Trichomonas urethritis);

- infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infections of bones and joints, central nervous system (CNS) infections, including bacterial endocarditis, pneumonia, empyema and lung abscess;

- infections caused by 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, pararectal area, appendectomy, gynecological operations);

- radiation therapy of patients with tumors - as a radiosensitizing agent, in cases where tumor resistance is caused by hypoxia in tumor cells.

Contraindications:

- Hypersensitivity to the drug;

- leukopenia (including in the anamnesis);

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

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

- deficiency of sugar / isomaltase, intolerance to fructose, glucose-galactose malabsorption;

- children's age (up to three years).

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

Carefully:

Carefully prescribe to patients with renal / hepatic insufficiency and a diabetic patient (due to the presence of sugar).

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.

Pregnancy and lactation:

Contraindicated in the first trimester of pregnancy and lactation.

Application in II and III trimester of pregnancy and lactation is possible that if the benefit to the mother outweighs the risk of side effects in the fetus and child.

If it is necessary to prescribe the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

The drug should be taken orally, during or after a meal (or with milk), without chewing.

With trichomoniasis - 250 mg (1 tablet) 2 times a day for 10 days. Women need to be additionally appointed metronidazole in the form of vaginal suppositories or tablets.

If necessary, you can repeat the course of treatment or increase the dose to 0.75-1.0 g / day. (3-4 tablets).Between the courses should be a break in 3-4 weeks with the implementation of repeated control laboratory tests. An alternative scheme of therapy is the appointment of 2 g (8 tablets) once to the patient and his sexual partner.

Children older than 10 years - 500 mg / day (2 tablets). The daily dose should be divided into 2 divided doses. The course of treatment is 10 days.

With chronic amebiasis daily dose of 1.5 g (6 tablets) in 3 divided doses for 5-10 days. In acute amoebic dysentery daily dose of 2.25 g (9 tablets) in 3 divided doses until symptoms stop.

With liver abscess the maximum daily dose of 2.5 g (10 tablets) in 1 or 2-3 doses, for 3-5 days, in combination with antibiotics (tetracyclines) and other therapies.

Children 7-10 years - 1/2 dose of an adult.

With ulcerative stomatitis adults are prescribed 500 mg (2 tablets) 2 times a day for 3-5 days.

Children in this case, the drug is not shown.

With pseudomembranous colitis - 500 mg (2 tablets) 3 times a day. The course of treatment is 14 days.

For eradication Helicobacter pylori - 500 mg (2 tablets) 3 times a day for 7 days (as part of combination therapy, for example, combination with amoxicillin 2.25 g / day).

For the prevention of infectious complications - 750-1500 mg / day (3-6 tablets) in 3 divided doses 3-4 days before surgery, or once 1.0 g (4 tablets) on the first day after the operation. 1-2 days after the operation (when already allowed ingestion) - 750 mg / day (3 tablets) for 7 days.

With severe renal dysfunction (creatinine clearance less than 10 ml / min) daily dose should be halved.

Side effects:

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

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 of movements, ataxia, dysarthria, gait disorders, nystagmus, tremor) that are reversible after metronidazole withdrawal, 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 the contours of objects, reduced visual acuity, impaired color perception, neuropathy / optic neuritis.

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 / (because of the growth of fungal microflora).

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 metronid-ash metabolite, 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 or swelling at the injection site) (for parenteral dosage forms).

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

If any of the side effects indicated in the manual are aggravated, or any other side effects not indicated in the instructions are noted, you should inform the doctor immediately.

Overdose:

Symptoms: nausea, vomiting, ataxia; when receiving as a radiosensitizing agent - convulsions, peripheral neuropathy.

Treatment: there is no specific antidote, symptomatic and supportive therapy.

Interaction:

Metronidazole 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, resulting in reduced its concentration in the plasma.

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

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.

In 1 tablet contains 44.5 mg of carbohydrates (starch and sugar), which corresponds to 0,0037 bread unit (XE). This should be taken into account by patients with diabetes mellitus.

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 dangerous activities that require increased concentration and speed of psychomotor reactions, with dizziness, coordination of movement, increased excitability, weakness, headache.

Form release / dosage:Tabletki, 250 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and foil of aluminum printed lacquered or paper with a polymer coating.

For 10 tablets in a contour non-cellular package of paper with a polymer coating.

1, 2, 3, 4 or 5 contour packs with instructions for use are placed in a cardboard pack.

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:

3 years.

Do not use the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002814 / 01

Date of registration:05.02.2010 / 09.12.2015

Expiration Date:Unlimited

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp25.04.2018

Illustrated instructions

Instructions

Metronidazole MS (Metronidazole MS)