Metronidazole

General characteristics. Structure:

Active ingredient: 0,25 g of metronidazole.

Excipients: potato starch, stearic acid, talc.

Pharmacological properties:

Pharmacodynamics. 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 histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp is active concerning Trichomonas vaginalis., and also strict anaerobes of Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (P.bivia, P.buccae, P.disiens), and some gram-positive microorganisms (Eubacterium spp., Clostridium 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) of 1-3 h. Communication with proteins of plasma of 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 of 8 h (from 6 to 12 h), at alcoholic damage of a liver of 18 h (from 10 to 29 h), at newborns: 28-30 weeks about 75 h which were born at duration of gestation, respectively, 32-35 weeks 35 h, 36-40 weeks 25 h. It is removed to kidneys of 60-80% (20% in not changed look), through intestines of 6-15%.

Renal clearance of 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 of 250 mg/days; 5-10 years of 250-375 mg/days, are more senior than 10 years of 500 mg/days. The daily dose should be divided into 2 receptions. Course of treatment of 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). Course of treatment of 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 of 1,5 g in 3 receptions within 5-10 days, at acute amoebic dysentery of 2,25 g in 3 receptions before the termination of symptoms.

At liver abscess the maximum daily dose of 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 of 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.

Others: 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 (II-III trimesters), renal/liver failure

Storage conditions:

List B. To store in dry, protected from light and the place, unavailable to children. A period of validity - 2 years. After a period of validity not to apply.

Issue conditions:

According to the recipe

Packaging:

Tablets of 250 mg. On 10 tablets in planimetric bezjyacheykovy packaging. On 10, 20, 30 tablets in a blister strip packaging. On 20, 30 tablets in glass jars of dark glass or banks polymeric. Each can or 1, 2, 3, 10 planimetric packagings together with the instruction are placed in a pack from a cardboard. On 700 planimetric bezjyacheykovy packagings with application instructions place in group packaging.