Metronidazole

General characteristics. Structure:

Active ingredient: 250 mg of metronidazole in each tablet.

Excipients: talc, stearic acid, polyvinyl alcohol, potato starch.

Pharmacological properties:

Pharmacodynamics. Antiprotozoan and antibacterial drug, derivative 5-nitro-imidazole. The mechanism of action consists in biochemical recovery 5 nitrogroups of metronidazole intracellular transport proteins of anaerobic microorganisms and protozoa. The recovered 5 nitrogroup of metronidazole interacts with DNA of a cell of microorganisms, inhibiting synthesis of their nucleic acids that leads to death of bacteria.

Entamoeba histolytica, and also gram-negative anaerobe bacterias of Bacteroides spp is active concerning Trichomonas vaginalis. (including B. fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus), Fusobacterium spp. and some gram-positive anaerobe bacterias (sensitive strains of Eubacterium spp., Clostridium spp., Peptococcus niger, Peptostreptococcus spp.). MPK for these strains makes 0,125 - 6,25 mkg/ml.

Shows activity concerning Helicobacter pylori (however, in 40% of cases the carriage metronidazole resistant strains is possible).

To metronidazole aerobic microorganisms and facultative anaerobes, but in the presence of the mixed flora are insensitive (aerobes and anaerobe bacterias) metronidazole works sinergidno with antibiotics, effective against usual aerobes.

Increases sensitivity of tumors to radiation, causes disulfiramopodobny reactions

Pharmacokinetics. Absorption - high (bioavailability not less than 80%). Has high penetration, reaching bactericidal concentration in the majority of fabrics and liquids of an organism, including lungs, kidneys, a liver, skin, cerebrospinal fluid, a brain, bile, saliva, amniotic liquid, cavities of abscesses, a vaginal secret, semen, breast milk, gets through a blood-brain barrier and a placental barrier. Distribution volume: adult - about 0,55 l/kg, newborn – 0,54 – 0,81 l/kg.

Cmax makes from 6 to 40 mkg/ml depending on a dose and is reached in 1 - 3 h. Communication with proteins of plasma – 10-20%.

It is metabolized ≅ 30-60% of metronidazole by a hydroxylation, oxidations and a glyukuronirovaniye. The main metabolite (2 oxymetronidazole) also has antiprotozoan and antimicrobic effect.

T½ at normal function of a liver is 8 h (from 6 to 12 h), at alcoholic damage of a liver - 18 h (from 10 to 29 h), at newborns: been born at duration of gestation – 28 - 30 weeks - about 75 h, 32 - 35 weeks - 35 h, 36 - 40 weeks - 25 h. It is removed by kidneys of 60 - 80% (20% in not changed look), through intestines – 6 – 15%.

Renal clearance – 10,2 ml/min. At patients with a renal failure after repeated introduction the metronidazole kumulirovaniye in blood serum can be observed (therefore at patients with a heavy renal failure the frequency of reception should be reduced).

Metronidazole and the main metabolites quickly are removed from blood at a hemodialysis (T1/2 is reduced to 2,6 h). At peritoneal dialysis it is removed in insignificant quantities.

Indications to use:

In order to avoid development of resistance of microorganisms metronidazole has to be applied only to treatment of the infections caused metronidazole - sensitive strains (according to a microbiological research of material or to epidemologichesky data).

Trichomoniasis with clinical symptoms - at women and men in case of laboratory confirmation of the diagnosis (a research of a smear and/or culture).

Asimptomny trichomoniasis - at women with an endocervicitis, a cervicitis or an erosion of a neck of uterus. As presence of trichomonads can prevent exact assessment of cytologic smears, additional smears have to be executed after an eradikation of a parasite.

Treatment of the spouse without clinical manifestations. Partners without symptoms of a disease have to be treated at the same time for prevention of repeated infection. The decision on treatment of the male partner without clinical manifestations in which trichomonads are not found (or the analysis was not carried out) is accepted by the doctor. At repeated infection of the spouse have to be treated with metronidazole at the same time.

Amebiasis. Treatment of an acute intestinal amebiasis (amoebic dysentery) and the abscess of a liver caused by amoebas (including with aspiration or drainage of abscess).

Mephitic bacterial gangrenes, including the infections caused by Bacteroides including a type of B. fragilis (B.fragilis, B.distasonis, B. ovatus, B.thetalotaomicron, B. vulgatus), Clostridium spp., Eubacterium spp., Peptococcus niger and Peptostreptococcus. Treatment of the heavy infections caused by sensitive anaerobic bacteria in combination with surgical treatment. In case of the mixed aerobic and mephitic gangrene, in addition use antibacterial agents, active concerning aerobic bacteria.

The infections of skin and appendages caused by Bacteroides (including V. fragilis), Clostridium spp., Peptococcus niger, Peptostreptococcus spp. and Fusobacterium spp.

Gynecologic infections, including an endometritis, an endomyometritis, tubo-ovarian abscess and infections after ginekologchesky operations caused by Bacteroides (including V. fragilis), Clostridium spp., Peptococcus niger, Peptostreptococcus spp.

The bacterial septicaemia caused by Bacteroides (including V. fragilis), Clostridium spp.

The infections of bones and joints caused by types of Bacteroides (including V. fragilis), as additional therapy.

Infections of the central nervous system, including meningitis and abscess of a brain, a lower respiratory tract infection, including pneumonia, an empyema and abscess of a lung; an endocarditis, the caused Bacteroides (including V. fragilis).

Route of administration and doses:

Accept inside, in time or after food (or washing down with milk), without chewing.

Trichomoniasis at women and men. The course of treatment is chosen individually. A one-day course of treatment - 2 g (8 tablets) in the form of a single dose or separately on two receptions on 1 gram (4 tablets) 2 times a day. One-day treatment is shown when there is an assumption that the patient cannot precisely observe the scheme of treatment;

Seven-day course of treatment – on 250 mg (½ tablets) three times a day within seven days. Frequency of treatment can be higher after a seven-day course of treatment.

Reception of metronidazole during the first trimester of pregnancy is contraindicated to pregnant women. Carrying out is contraindicated to pregnant women of a one-day course of therapy as it results in high concentration of metronidazole in a blood plasma and can get into a fruit organism.

At repeated courses of treatment metronidazole, it is recommended to take a break in 4 - 6 weeks. Before and after the specified courses it is necessary to make blood test on total quantity of leukocytes and a leukocytic formula.

Amebiasis. Adults: at an intestinal amebiasis on 750 mg (1½ tablets) inside three times a day within 5-10 days; at liver abscess on 500 mg or 750 mg three times a day from 5 to 10 days. Children: the daily dose of 35 - 50 mg/kg divided into three intakes within 10 days.

For treatment of heavy mephitic bacterial gangrenes metronidazole is appointed at the initial stage. A usual dose for adult 7,5 mg/kg each six hours in (about 500 mg for the patient weighing 70 kg). Maximum daily dose of 4 g. Duration of therapy from 7 to 10 days (treatment of infections of bones and joints, lower respiratory tracts and an endocardium can be longer).

At elderly patients, the pharmacodynamics of metronidazole can be changed, monitoring of content of metronidazole in blood serum is necessary to pick up a dose.

At patients with a serious illness of a liver cumulation of metronidazole is possible and its doses have to be reduced. Careful monitoring of level of metronidazole in plasma and toxicity signs is recommended. At an anury the dose decline as metronidazole and its metabolites, are removed by means of dialysis is not required.

Features of use:

During treatment ethanol reception is contraindicated (possibly development of disulfiramopodobny reactions: abdominal pain of spastic character, nausea, vomiting, a headache, sudden "inflows" of blood to the person).

At long therapy it is necessary to control a pattern of peripheral blood. At a leukopenia the possibility of continuation of treatment depends on risk of development of infectious process.

Emergence of an ataxy, dizziness and any other deterioration in the neurologic status of patients demands the treatment termination.

Can immobilize treponemas and lead to the false positive test of Nelson.

Metronidazole can influence definition of such biochemical indicators as aspartate aminotransferase (nuclear heating plant), alaninaminotranspherase (ALT), a lactate dehydrogenase (LDG), triglycerides, a glucose hexokinase.

Paints urine in dark color.

At treatment of a mecotic vaginitis at women and a mecotic urethritis at men it is necessary to abstain from sex life. After therapy it is necessary to carry out control tests during 3 next cycles before and after periods.

Use at pregnancy in the period of a lactation. Reception of metronidazole during the first trimester of pregnancy is contraindicated. In the II-III trimesters, in case of need, metronidazole can be appointed taking into account advantage/risk. Metronidazole renders teratogenic effect, gets through a placental barrier and quickly gets to a fruit blood stream. Adequate and well controlled researches at pregnant women are not conducted. Because metronidazole has carcinogenicity at rodents, this means can be used at pregnancy only in urgent cases.

Use of metronidazole for treatment of trichomoniasis during pregnancy has to be limited to cases at which alternative treatment is inefficient.

In need of purpose of metronidazole in the period of a lactation it is necessary to stop breastfeeding. Metronidazole cosecretes in human milk in concentration, the corresponding subjects which contain in plasma.

Influence on ability to drive the car and potentially dangerous mechanisms. Development of dizziness, the confusion of consciousness, hallucinations or convulsions connected with reception of this drug that breaks operator activity is possible.

Side effects:

Serious reactions: convulsive attacks, encephalopathy, aseptic meningitis, optical and peripheral neuropathy (with numbness or paresthesia of extremities). At emergence of any neurologic symptoms, it is necessary to stop reception of metronidazole and to see immediately a doctor.

Frequent side reactions: disorders of digestive tract (nausea at 12% of patients, vomiting, anorexia, diarrhea, discomfort in epigastric area, spastic abdominal pains, a lock) a headache.

Also following side reactions are possible:

Oral cavity: sharp, unpleasant metal smack in a mouth, feeling of "roughness" of language, a glossitis, stomatitis. These symptoms can be connected with growth of fungi of the sort Candida during therapy.

Hemopoietic frustration: reversible neutropenia (leukopenia); persistent thrombocytopenia.

Cardiovascular frustration: flattening of the T-tooth on an ECG.

Disorders of the central nervous system: encephalopathy, aseptic meningitis, convulsive attacks, optical neuropathy, peripheral neuropathy, dizziness, lack of coordination, ataxy, confusion of consciousness, dysarthtia, irritability, depression, weakness, sleeplessness.

Hypersensitivity: urticaria, erythematic rash, Stephen-Johnson's syndrome, a toxic epidermal necrolysis, feeling of inflows, a nose congestion, dryness in a mouth (a vagina or a vulva), fever.

Renal failure: a dysuria, cystitis, a polyuria, an urine incontience, feeling of tension in the field of a basin. Dark color of urine probably caused by a metabolite (frequency: 1 case from 100000).

Others: growth of fungi of the sort Candida in a vagina, a dispareuniya, decrease a libido, a proctitis and short-term joint pains. At the use of alcoholic beverages with metronidazole abdominal pains, nausea, vomiting, reddening of integuments or a headache are possible. Change of taste of alcoholic beverages is possible, it is rare – development of pancreatitis.

In experiments on rats and mice metronidazole had cancerogenic effect. At patients with a disease Krone development of gastrointestinal cancer and other options of ekstraintestinalny cancer is possible (development of a breast cancer and a large intestine when using metronidazole in high doses during a long span is possible). Metronidazole is not recommended for use for patients with a disease Krone.

Interaction with other medicines:

Strengthens effect of indirect anticoagulants that leads to increase in a prothrombin time.

Similar to Disulfiramum causes intolerance of ethanol.

Simultaneous use with Disulfiramum can lead to development of various neurologic symptoms (an interval between reception - not less than 2 weeks).

Cimetidinum suppresses metronidazole metabolism that can lead to increase in its concentration in blood serum and to increase in risk of development of by-effects.

Co-administration of the means stimulating enzymes of a microsomal oxidation (phenobarbital, Phenytoinum) can accelerate elimination of metronidazole and reduce its concentration in plasma.

At a concomitant use with drugs of lithium (Li+) concentration of the last in plasma and development of symptoms of intoxication can increase.

It is not recommended to combine with not depolarizing muscle relaxants (a vekuroniya bromide).

Streptocides strengthen antimicrobic effect of metronidazole.

Contraindications:

Hypersensitivity, leukopenia (including in the anamnesis), organic lesions of the central nervous system (including epilepsy), a liver failure (in case of purpose of high doses), pregnancy (the I trimester), the lactation period; children's age (up to 3 years).

With care: pregnancy (II-III trimesters), renal/liver failure.

Overdose:

Symptoms: nausea, vomiting, ataxy; at reception as the radio sensibilizing means - spasms, peripheral neuropathy.

Treatment: the specific antidote is absent, a symptomatic and maintenance therapy.

Storage conditions:

In the place protected from light and moisture, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging. On 1 or 2 blister strip packagings together with a leaf insert in a pack from a cardboard.