Metronidazole

General characteristics. Structure:

Active agent: metronidazole of 250,0 mg

Excipients: starch corn - 37,7 mg, povidone - 12,0 mg, magnesium stearate - 0,3 mg.

Pharmacological properties:

Antiprotozoan and antimicrobic drug, derivative 5 nitroimidazoles. The mechanism of action consists in biochemical recovery 5 nitrogroups intracellular transport proteins of anaerobic microorganisms and protozoa, the recovered 5 nitrogroup interacts with deoxyribonucleic acid (DNA) of a cell of microorganisms, inhibiting synthesis of their nucleic acids that leads to death of bacteria.
Entamoeba histolica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp is active concerning Trihomonas vaginalis., and also strict anaerobes of Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonela spp., Prevotella (P. bivia, P/of buccae, disiens P/), and some gram-positive microorganisms (Eubacterium spp., Clotridium spp., Peptococcus spp., Peptostreptococcus spp.). The minimum overwhelming concentration for these strains makes 0.125-6.25 mkg/ml. In combination with amoxicillin shows activity concerning Helicobacter pylori (Amoxicillin suppresses development of resistance to metronidazole).
Aerobic microorganisms and facultative anaerobes, but in the presence of the mixed flora are not sensitive to metronidazole (aerobes and anaerobe bacterias) Metronidazole works synergy with antibiotics, effective against usual aerobes.
Increases sensitivity of tumors to radiation, causes a sensitization to alcohol (disulfiramopodobny action), stimulates reparative processes.

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 and placental barrier. Distribution volume: adult - about 0.55 l/kg, newborn-0.54-0.81 l/kg. The maximum concentration of drug in blood (Cmax) makes from 6 to 40 mkg/ml depending on a dose. Time of achievement of the maximum concentration (Tcmax) - 1-3 h. Communication with proteins of plasma - 10-20%. In an organism about 30-60% of metronidazole by a hydroxylation, oxidations and a glyukuronirovaniye are metabolized. The main metabolite (2 oxymetronidazole) also has antiprotozoan and antimicrobic effect.
Elimination half-life (T1/2) at normal function of a liver - 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, respectively, 3235 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:

Protozoan infections: an abenteric amebiasis, including amoebic abscess of a liver, an intestinal amebiasis (amoebic dysentery), trichomoniasis, гиардиазис, a balanthidiasis, a lambliasis, a skin leushmaniosis, a mecotic vaginitis, a mecotic urethritis.
The infections caused by Bacteroides spp. (including V. of fragilis, V. of distasonis, V. of ovatus, V. of thetaiotaomicron, V. vulgatus): infections of bones and joints, infections of the central nervous system (CNS), including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and abscess of lungs. The infections caused by types of Bacteroides including the fragilis group B., types of Clostridium, Peptococcus and Peptostreptococcus: infections of an abdominal cavity (peritonitis, liver abscess), infections of bodies of a basin (an endometritis, an endomyometritis, abscess of fallopian pipes and ovaries, infections of a vault of the vagina after surgeries), infections of skin and soft tissues. The infections caused by types of Bacteroides including the Fragilis group B. and types of Clostridium: sepsis.
The pseudomembranous colitis (connected using antibiotics).
The gastritis or ulcer of a duodenum connected about Helicobacter pylori, alcoholism. Prevention of postoperative complications (especially interventions on a colon, okolorektalny area, appendectomy, gynecologic operations).
Radiation therapy of patients with tumors - as the radio sensibilizing means, in cases when resistance of a tumor is caused by a hypoxia in tumor cells.

Route of administration and doses:

Inside, in time or after food, (or washing down with milk), without chewing.
At trichomoniasis - on 250 mg 2 times a day within 10 days or on 400 mg 2 times a day within 5-8 days. Women need to appoint in addition metronidazole in the form of vaginal candles or tablets. If necessary, it is possible to repeat a course of treatment or to raise a dose to 0.75-1 g/days. Between courses it is necessary to take a break in 3-4 weeks with carrying out repeated control laboratory researches. The alternative scheme of therapy is appointment on 2 g once to the patient and his sexual partner.
Children are 2-5 years old - 250 mg/days; 5-10 years - 250-375 mg/days, are more senior than 10 years - 500 mg/days. The daily dose should be divided into 2 receptions. A course of treatment - 10 days.
At a lambliasis - on 500 mg 2 times a day within 5-7 days.
To children till 1 year - on 125 mg/days, 2-4 years - on 250 mg/days, 5-8 years - on 375 mg/days, 8 years - on 500 mg/days are more senior (in 2 receptions). A course of treatment - 5 days. At a giardiazisa - on 15мг/кг/сут in 3 receptions within 5 days.
Adult: at an asymptomatic amebiasis (at detection of a cyst) a daily dose of-1-1.5 g (on 500 mg 2-3 times a day) within 5-7 days. At a chronic amebiasis a daily dose - 1.5 g in 3 receptions within 5-10 days, at acute amoebic dysentery - 2.25 g in 3 receptions before the termination of symptoms.
At liver abscess - the maximum daily dose - 2.5 g in 1 or 2-3 receptions, within 3-5 days, in a combination with antibiotics (tetracyclines), etc. by therapy methods.
To children of 1-3 years-1/4 doses of the adult, 3-7 years-1/3 doses of the adult, 7-10 years-1/2 doses of the adult. At a balanthidiasis - 750 mg 3 times a day within 5-6 days.
At a stomacace the adult appoint 500 mg 2 times a day within 3-5 days; in this case drug is not shown to children. At pseudomembranous colitis - on 500 mg 3-4 times a day.
For Helicobacter pylory eradikation - on 500 mg 3 times a day within 7 days (as a part of a combination therapy, for example, combinations with amoxicillin of 2.25 g/days).
At treatment of a mephitic gangrene maximum daily dose of-1.5-2 g. At treatment of an alcoholism appoint 500 mg/days to the period till 6 (no more) months. For prevention of infectious complications - on 750-1500 mg/days in 3 receptions in 3-4 days prior to operation, or once 1 g in the first days after operation. In 1-2 days after operation (when intake is already allowed) - on 750 mg/days within 7 days.
At the expressed renal failures (KK less than 10 ml/min.) the daily dose has to be reduced twice.

Features of use:

During treatment ethanol reception is contraindicated (possibly development of disulfiramopodobny reaction: spastic abdominal pains, nausea vomiting, a headache, sudden rush of blood to the person).
In a combination with amoxicillin it is not recommended to apply at patients more young than 18 years. At long therapy it is necessary to control a blood pattern.
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. 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. Simultaneous treatment of sexual partners is obligatory. Treatment does not stop during periods. After therapy of trichomoniasis it is necessary to carry out control tests during three next cycles before and after periods. After treatment of a lambliasis if symptoms remain, in 3-4 weeks to carry out 3 analyses a bucketed calla in several days (some successfully treated patients have a lactose intolerance caused by an invasion, can remain within several weeks or months, reminding lambliasis symptoms). In the period of a lactation it is recommended to stop breastfeeding.

Side effects:

- From the alimentary system: diarrhea, anorexia, nausea, vomiting, intestinal colic, locks, "metal" smack in a mouth, dryness in a mouth, a glossitis, stomatitis, pancreatitis.
- From a nervous system: dizziness, incoordination of movements, ataxy, confusion of consciousness, irritability, depression, hypererethism, weakness, sleeplessness, headache, spasms, hallucinations, peripheral neuropathy.
- Allergic  reactions:  urticaria,  skin rash, dermahemia, nose congestion, fever, arthralgias.
- From urinogenital system: a dysuria, cystitis, a polyuria, an urine incontience, candidiasis, coloring of urine in red-brown color. Other: a neutropenia, a leukopenia, flattening of a tooth of T on the electrocardiogram.

Interaction with other medicines:

Strengthens effect of indirect anticoagulants that leads to increase in time of formation of a prothrombin.
Similar to Disulfiramum, causes intolerance of ethanol. Simultaneous use with Disulfiramum can lead to development of various neurologic symptoms (an interval between appointment - not less than 2 weeks). Cimetidinum inhibits 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 drugs stimulating enzymes of a microsomal oxidation in a liver (phenobarbital, Phenytoinum) can accelerate metronidazole elimination therefore its concentration in plasma goes down. At a concomitant use with lithium drugs, 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 TsNS (including epilepsy), a liver failure (in case of purpose of high doses), pregnancy (the I trimester), the lactation period. With care - pregnancy (the II-III trimesters), a renal/liver failure.

Overdose:

There are no data.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets on 250 mg.
On 10, 20 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 10, 20, 30, 40, 50, 60 or 100 tablets in banks polymeric for medicines. To one bank or 1, 2, 3, 4, 5, 6, 8 or 10 blister strip packagings together with the application instruction place in cardboard packaging (pack).