Трихопол®

General characteristics. Structure:

Active ingredient: 250 mg of metronidazole.

Excipients: potato starch, gelatin, starch syrup, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Metronidazole is derivative 5 nitroimidazoles with antiprotozoan and antibacterial action. The mechanism of action consists in biochemical recovery 5 nitrogroups 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.

Metronidazole is active in the relation: Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., and also strict anaerobes of Bacteroides spp. (including, Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella (Prevotella bivia, Prevotella buccae, Prevotella disiens) and some gram-positive microorganisms (Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). The Minimum Overwhelming Concentration (MOC) 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).

Metronidazole has no bactericidal effect concerning the majority of aerobic bacteria and facultative anaerobes, fungi and viruses. In the presence of the mixed flora (aerobes and anaerobe bacterias) metronidazole works sinergidno with antibiotics, effective against usual aerobes.

Increases sensitivity of tumors to radiation, causes a sensitization to alcohol (disulfiramopodobny action), stimulates reparative processes.

Pharmacokinetics. Metronidazole quickly and almost is completely soaked up from a digestive tract, bioavailability not less than 80%. Existence of food reduces the speed of absorption and the maximum concentration of metronidazole in blood serum. Less than 20% of drug contact serum proteins.

Metronidazole gets into 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 hematoencephalic and placental barrier. Distribution volume at adults makes about 0,55 l/kg, newborns have 0,54 – 0,81 l/kg.

The maximum concentration of metronidazole in blood is reached in 1-3 hours. About 30 - 60% of metronidazole are metabolized by a hydroxylation, oxidation and interaction with glucuronic acid. The main metabolite of metronidazole (2 oxymetronidazole) also shows antibacterial and antiprotozoan action.

The elimination half-life (T1/2) at normal function of a liver averages 8 h (from 6 to 12 h); at alcoholic damage of a liver – 18 h (from 10 to 29 h); at the newborns who were born at duration of gestation of 28 - 30 weeks – about 75 h; 32 – 35 weeks – 35 h, 36 – 40 weeks – 25 h, respectively.

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. It is removed by kidneys of 60 - 80% of metronidazole (20% in not changed look), through intestines – 6 - 15% of the applied dose. The renal clearance of drug makes 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).

Renal removal of metronidazole decreases at patients of advanced age.

Indications to use:

• trichomoniasis;
• bacterial vaginosis;
• all forms of an amebiasis (a disease of intestinal and abenteric localization, including amoebic abscess of a liver, amoebic dysentery, and also an asymptomatic amebiasis);
• lambliasis;
• periodontium infections (including, acute ulocace, acute dontogenous infections);
• the mephitic bacterial gangrenes (gynecologic and abdominal infections, infections of the central nervous system, bacteremia, sepsis, an endocarditis, infections of bones and joints, skin and soft tissues, respiratory infection) caused by Bacteroides spp., Clostridium spp., Eubacterium spp., Peptococcus spp., Peptostreptococcus spp. and other anaerobe bacterias sensitive to metronidazole.
• treatment of infections of Helicobacter pylori at a peptic ulcer of a 12-perstny gut or a stomach in combination with drugs of bismuth and an antibiotic, for example, amoxicillin.
• preventive appointment before surgical intervention on digestive tract and reproductive organs.

Route of administration and doses:

Inside, in time or after food, without chewing. Trichomoniasis. Adults and children are more senior than 10 years: on 250 mg (1 tablet) 3 times a day or 500 mg (2 tablets) 2 times a day within 7 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. 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 purpose of 750 mg (3 tablets) in the morning and 1250 mg (5 tablets) in the evening or on 2000 mg (8 tablets) in the form of a single daily dose. Duration of treatment makes 2 days.

Treatment is carried out at the same time at both sexual partners. Children: from 3 to 7 years – 125 mg (1/2 tablets) 2 times a day; from 7 to 10 years – 125 mg (1/2 tablets) 3 times a day. The course of treatment makes 7 days.

Bacterial vaginosis. Adults: on 500 mg (2 tablets) 2 times a day within 7 days or 2000 mg (8 tablets) in the form of a single dose. Simultaneous treatment of the sexual partner is not required.

Amebiasis. Invasive forms of an amebiasis of intestines at susceptible patients (including, amoebic dysentery). Adults and children are more senior than 10 years: on 750 mg (3 tablets) 3 times a day. Children: from 3 to 7 years – 250 mg (1 tablet) 4 times a day;
from 7 to 10 years – 375 mg (1,5 tablets) 3 times a day. The course of treatment makes usually 5 days.

Intestines amebiasis at less susceptible patients and at chronic amoebic hepatitis. Adults and children are more senior than 10 years: on 375 mg (1,5 tablets) 3 times a day. Children: from 3 to 7 years – 125 mg (1/2 tablets) 4 times a day; from 7 to 10 years – 250 mg (1 tablet) 3 times a day. Duration of a course of treatment makes 5 – 10 days.

Amoebic abscess of a liver and other forms of an abenteric amebiasis. Adults and children are more senior than 10 years: on 375 mg (1,5 tablets) 3 times a day. Children: from 3 to 7 years – 125 mg (1/2 tablets) 4 times a day; from 7 to 10 years – 250 mg (1 tablet) 3 times a day. The course of treatment makes 5 days.

Asymptomatic carriage of cysts. Adults and children are more senior than 10 years: on 375 – 750 mg (1,5 – 3 tablets) 3 times a day. Children: from 3 to 7 years – 125 mg (1/2 tablets) 4 times a day; from 7 to 10 years – 250 mg (1 tablet) 3 times a day. Duration of a course of treatment makes 5 – 10 days.

Lambliasis. Adults and children are more senior than 10 years: on 500 mg (2 tablets) 2 times a day within 5 - 7 days; or on 2000 mg (8 tablets) of 1 times a day within 3 days. Children: from 3 to 7 years – 250 - 375 mg (1 – 1,5 tablets) of 1 times a day within 5 days or 500 - 750 mg (2 – 3 tablets) of 1 times a day within 3 days; from 7 to 10 years – 250 mg (1 tablet) 2 times a day within 5 days or 1000 mg (4 tablets) of 1 times a day within 3 days.

Periodontium infections. Acute ulocace. Adults and children are more senior than 10 years: on 250 mg (1 tablet) 3 times a day. Children: from 3 to 7 years – 125 mg (1/2 tablets) 2 times a day; from 7 to 10 years – 125 mg (1 tablet) 3 times a day. Duration of a course of treatment makes 3 days.

Acute dontogenous infections. Adults and children are more senior than 10 years: on 250 mg (1 tablet) 3 times a day within 3 - 7 days.

The infections caused by anaerobic bacteria. Treatment of mephitic gangrenes is usually begun with intravenous infusions. As soon as it becomes possible, treatment has to be continued by tablets. Adults and children are more senior than 10 years: on 500 mg (2 tablets) 3 – 4 times a day. To children 10 years at treatment of mephitic gangrenes are younger use of infusion solutions of metronidazole is recommended. Duration of treatment should not exceed 7 days.

Eradikation Helicobacter pylori. On 500 mg (2 tablets) 3 times a day within 7 days (as a part of a combination therapy, for example, with amoxicillin of 2,25 g a day).

Prevention of the infections caused by anaerobic bacteria (before surgeries on a stomach cavity, in gynecology and obstetrics). Adults and children are more senior than 12 years: on 250 – 500 mg (1 – 2 tablets) 3 times a day in 3 - 4 days prior to operation. In 1 – 2 day after operation (when intake is already allowed) on 250 mg (1 tablet) 3 times a day within 7 days.

At the expressed renal failures (clearance of creatinine less than 10 ml/min.) the daily dose of metronidazole has to be reduced twice.

Features of use:

Patients with a heavy liver failure should appoint metronidazole with care as as a result of metabolism delay concentration of metronidazole and its metabolites increases in plasma.

Because of delay of excretion it is required to be careful at the choice of a dose of metronidazole at patients with a renal failure. At such patients the dose needs to be reduced by a half.

Metronidazole has to be applied with extra care at patients with oppression of marrow and central nervous system, and also at elderly patients. Emergence of an ataxy, dizziness and any other deterioration in the neurologic status of patients demands the treatment termination.

At long therapy by metronidazole (more than 10 days) it is necessary to control a pattern of peripheral blood and function of a liver.

At a leukopenia the possibility of continuation of treatment depends on risk of development of infectious process.

In a combination with amoxicillin 18 years are not recommended to use drug at patients more young.

It is necessary to avoid use of metronidazole for patients with a porphyria.

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

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. 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 it is necessary 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).

Patients need to abstain from alcohol intake during therapy by metronidazole, and also within, at least, 48 hours after completion of treatment, because of a possibility of development of disulfiramopodobny reactions: abdominal pain of spastic character, nausea, vomiting, a headache, sudden rush of blood to the person.

During treatment by metronidazole urine can have dark or red-brown coloring in connection with presence of water-soluble dyes.

Influence of drug on driving of the car and performance of the work demanding the high speed of mental and physical reactions. At administration of drug it is necessary to avoid potentially dangerous types of activity requiring special attention, bystry mental and motor reaction, especially driving of vehicles and service of mechanisms.

Use during pregnancy and feeding by a breast. Metronidazole gets through a placenta therefore it is not necessary to appoint drug in the first trimester of pregnancy, further it is necessary to apply only if the potential advantage of use of drug for mother, exceeds possible risk for a fruit.

As metronidazole gets into breast milk, reaching in it the concentration close to concentration in a blood plasma, it is recommended to stop breastfeeding during treatment by drug.

Side effects:

From digestive tract: epigastric pains, nausea, vomiting, diarrhea, locks, intestinal colic, a loss of appetite, anorexia, taste disturbance, unpleasant "metal" smack in a mouth, dryness in a mouth, a glossitis, stomatitis; very seldom — an aberration of results of tests for a functional condition of a liver, cholestatic hepatitis, jaundice, pancreatitis.

From the central nervous system: at prolonged use — a headache, dizziness, an incoordination of movements, an ataxy, peripheral neuropathy, a hyperexcitability, irritability, a depression, a sleep disorder, drowsiness, weakness; in some cases — confusion of consciousness, a hallucination, spasm; very seldom — encephalopathy.

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

Allergic reactions: skin rash, itch, small tortoiseshell, mnogoformny exudative erythema, nose congestion, fever.

From the musculoskeletal device: mialgiya, arthralgias.

From the hemopoietic system: leukopenia; seldom — an agranulocytosis, a neutropenia, thrombocytopenia, a pancytopenia.

Others: flattening of a tooth of T on an ECG; extremely seldom — ototoxicity; pustulous rashes.

Interaction with other medicines:

Metronidazole strengthens effect of warfarin and other anticoagulants of a coumarinic row therefore at co-administration of a dose of these drugs it is necessary to reduce. 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 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 drugs stimulating enzymes of a microsomal oxidation in a liver (phenobarbital, Phenytoinum) can accelerate metronidazole elimination therefore its concentration in plasma goes down.

At patients, it is long receiving treatment by lithium drugs in high doses, at reception of metronidazole increase in concentration of lithium in a blood plasma and development of symptoms of intoxication is possible.

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

At the combined reception of metronidazole and cyclosporine increase in concentration of cyclosporine in a blood plasma can be observed.

Metronidazole reduces clearance of a ftoruratsil that can cause increase in toxicity of the last.

Streptocides strengthen antimicrobic effect of metronidazole.

Contraindications:

• Hypersensitivity to metronidazole and other nitroimidazolny derivatives, and also to any other ingredients of drug;
• leukopenia (including in the anamnesis);
• organic lesions of the central nervous system (including epilepsy);
• liver failure (in case of purpose of high doses of drug);
• pregnancy (I trimester);
• lactation period;
• children's age up to 3 years (for this dosage form).

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

Overdose:

The lethal dose for the person is unknown. Too high doses can become the reason of strengthening of side effects, mainly, of nausea, vomitings and dizzinesses; in more hard cases the ataxy, paresthesias and spasms can be noted.

In case of poisoning to apply the symptomatic and supporting treatment. The specific antidote is absent.

Storage conditions:

List B. In the dry, protected from light place, at a temperature below 25 °C. To store in the place, unavailable to children. Not to use after the expiry date specified on packaging. A period of validity - 5 years.

Issue conditions:

According to the recipe

Packaging:

Tablets of 250 mg. 10 tablets in the blister from PVC / It is scarlet a foil. On 2 blisters together with the application instruction place in a cardboard pack.