Метронидал®

General characteristics. Structure:

Active ingredient: 500 mg of metronidazole (in terms of 100% substance).

Excipients: sodium chloride, sodium hydrophosphate, dinatrium эдетат, citric acid, water for injections.

Pharmacological properties:

Pharmacodynamics: Antiprotozoan and antimicrobic drug, derivative 5 nitroimidazoles. The mechanism of action consists in biochemical recovery 5 nitrogroups of intracellular transport proteins of anaerobic microorganisms and protozoa. The recovered 5 nitrogroup interacts with DNA of a cell of microorganisms, inhibiting synthesis of their nucleic acids that leads to death of bacteria.
^{Метронидал®} it is active in the relation:

- protozoa: Trichomonas vaginalis, Entamoeba histolytica, Giardia intestinalis, Lamblia spp.,

- anaerobic bacteria: Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Clostridium spp., Eubacterium spp., Fusobacterhtm spp., Peptococcus spp., Peptostreptococcus spp.), Prevotella spp. (including Prevotella bivia, Prevotella buccae, Prevotella disiens), Veillonella spp.;

- facultative anaerobes: Gardnerella vaginalis, Helicobacterpylori, Campylobacter spp., including Campylobacter jejuni.

Range of the minimum overwhelming concentration for these strains makes 0,125-6,25 mkg/ml.

Metronidazole in combination with amoxicillin shows activity concerning Helicobacter pylori (amoxicillin suppresses development of resistance to metronidazole).

To metronidazole aerobic microorganisms and facultative anaerobes, but in the presence of the mixed flora are insensitive (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: At intravenous administration of 500 mg within 20 min., the maximum concentration in blood serum is reached in 1 h and makes 35,2 mkg/ml; in 4 h and 8 h concentration make 33,9 mkg/ml and 25,7 mkg/ml, respectively. Usually, therapeutic concentration in blood serum remains during 6-8 h. At a normal bile production concentration of metronidazole in bile after intravenous administration can exceed considerably concentration in plasma. 

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 (GEB) and a placental barrier. Distribution volume: adult - about 0.55 l/kg, newborn 0.54-0.8) l/kg. Communication with % proteins plasmas-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 (Т½) at normal function of a liver - 8 h (from 6 to 12 h), at alcoholic damage of a liver of-18 h (from 10 to 29 h). At the newborns who were born at duration of gestation of 28-30 weeks, Т½ about 75 h at duration of gestation of 32-35 weeks - 35 h and at duration of gestation of 36-40 weeks - 25 h.
It is removed by kidneys - 60-80% (20% in not changed look) and 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 (the elimination half-life is reduced to 2.6 h). At peritoneal dialysis it is removed in insignificant quantities.

Indications to use:

- the infections caused by Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus)

- infections of bones and joints, infections of the central nervous system, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and abscess of lungs;

- the infections caused by types of Bacteroides including the Bacteroides fragilis group, and also types of Clostridium, Eubacterium, Peptococcus and Peptostreptococcus - infections of an abdominal cavity (peritonitis, intraabdominal abscess, 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, pelvic abscess), infections of skin and soft tissues (including postoperative wounds);

- sepsis/bacteremia, Bacteroides caused by types, including the Bacteroides fragilis and Clostridium spp group.

- the prevention of postoperative infectious complications (especially at interventions on colonic and direct guts, okolorektalny area, at gynecologic operations and abdominal organs, at appendectomy) which is carried out before operation, intraoperatsionno and after operation;

- protozoan infections: an abenteric amebiasis (including amoebic abscess of a liver), an intestinal amebiasis (amoebic dysentery), trichomoniasis, a mecotic vaginitis, a mecotic urethritis, a lambliasis (giardiasis), a balanthidiasis, a skin leushmaniosis;

- 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:

Intravenously to adults and children 12 years are more senior: in an initial dose of 0,5-1 g (infusion duration - 30-60 minutes), and then each 8 h on 0,5 g with a speed of 5 ml/min. A course of treatment - 7 days, but if necessary continue intravenous administration during longer time. The maximum daily dose - 4 g. At improvement of a condition of the patient according to indications carry out transition to the supporting intake in a dose on 0,4-0,5 g 3-4 times/days.

To children up to 12 years: metronidazole each 8 hours appoint according to the same scheme in a single dose 7,5 mg/kg (30-40 min.).

At it is purulent - septic diseases usually conduct 1 course of treatment.

For prevention of postoperative infectious complications - to adults and children 12 years are more senior appoint intravenously kapelno in a dose 15 mg/kg (about 1 g sick with the body weight of 70 kg) in 1 hour prior to operation (infusion duration - 30-60 minutes), then repeat intravenous drop administration of metronidazole in a dose of 7,5 mg/kg (about 0,5 g sick with the body weight of 70 kg) every 6 hours after the first administration of drug. In 1 - 2 day after operation (when intake is already allowed) - pass to metronidazole reception inside in a single dose 7,5 mg/kg (about 0,5 g sick with the body weight of 70 kg) each 6-8 hours within 7 days.

The patient with a chronic renal failure and with clearance of creatinine less than 30 ml/min. and/or a liver failure the maximum daily dose - no more than 1 g, frequency rate of use - 2 times a day.

As radio sensibilizing medicine enter in / вкапельно at the rate of 160 mg/kg or 4-6 g / кв.м body surfaces for 0,5-1,0 h prior to radiation. Apply before each session of radiation within 1-2 weeks. During the remained period of radiation therapy Metronidal do not apply. The maximum single dose should not exceed 10 g, course - 60 g. Apply drop introduction of 5% of solution of a dextrose, Haemodesum to removal of intoxication caused by radiation or 0,9% of solution of sodium of chloride.

At cancer of a neck of uterus, a carcinoma cutaneum use in the form of local applications (3 g dissolve in 10% dimethyl sulfoxide solution), moisten tampons which apply locally, for 1,5 - 2 h before radiation). At bad regression of a tumor of application carry out during all course of radiation therapy. At positive dynamics of clarification of a tumor from a necrosis - within the first 2 weeks of treatment.

Features of use:

During treatment ethanol reception is contraindicated (possibly development of disulfiramonodobny reaction: spastic abdominal pains, nausea, vomiting, a headache, sudden rush of blood to the person). 

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.

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 an urinary system: a dysuria, cystitis, a polyuria, an urine incontience, candidiasis, coloring of urine in red-brown color.

Local reactions: thrombophlebitis (pain, reddening or puffiness in the place of an injection).

Others: a neutropenia, a leukopenia, flattening of a tooth of T on an ECG.

Interaction with other medicines:

^{Метронидал®} it is not recommended to mix with other medicines or to use as solvent.

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 drugs of lithium 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 to metronidazole and other derivatives of 5 nitroimidazoles, a 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.

With care appoint at pregnancy (the II-III trimesters), a renal/liver failure.

 

Overdose:

There are no specific symptoms of overdose.

Treatment - the specific antidote is unknown. Therapy of overdose consists in the hemodilution supporting and symptomatic therapy. In hard cases use a hemodialysis.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C.
Freezing is not allowed. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

100 ml of drug in bottles or bottles glass with a capacity of 100 ml.
1 bottle or bottle with the application instruction are placed in a pack from a cardboard.