Klionum

General characteristics. Structure:

Active agent: metronidazole - 500 mg

Excipients: dihydrophosphate sodium a dihydrate, hydrophosphate sodium dodecahydrate, sodium chloride, water for injections.

Pharmacological properties:

Antiprotozoan and antimicrobic drug, derivative 5 nitroimidazoles. 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, Gardnerella vaginalis, Giardia intestinalis, and also strict anaerobes of Bacteroides spp is active concerning Trichomonas vaginalis. (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, Clostridium spp., Peptococcus spp., Peptostreptococcus spp.). MPK for these strains makes 0.125-6.25¼¬ú/ml. 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 disulfiramopodobny reactions, stimulates reparative processes.

Pharmacokinetics. Distribution: 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 0.54-0.81 l/kg. Cmax makes from 6 to 40 mkg/ml depending on a dose. Communication with % proteins plasmas-10-20. At in introduction of 500 mg within 20 min. Cmax in blood serum in 1 h - 35.2 mkg/ml.
Concentration of metronidazole in blood serum in 4 h - 33.9 mkg/ml, in 8 h - 25.7 mkg/ml; Cmin at the subsequent introduction - 18 mkg/ml. TCmax - 30-60 min., therapeutic concentration remains during 6-8 h. At a normal bile production concentration of metronidazole in bile in/in introductions can exceed later considerably concentration in plasma.

Biotransformation. 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.
Removal: An 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 the newborns who were 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%.
At the expressed renal failures (clearance of creatinine less than 10 ml/min.) at patients after repeated introduction the metronidazole kumulirovaniye in blood serum in this connection the dose of drug should be reduced twice can be observed.
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, a balanthidiasis, a lambliasis, a skin leushmaniosis, a mecotic vaginitis, a mecotic urethritis.
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, sepsis.

The infections caused by types of Clostridium spp., Peptococcus and Peptostreptococcus: infections of an abdominal cavity (peritonitis, liver abscess), infections of bodies of a small pelvis (endometritis, abscess of fallopian pipes and ovaries, infections of a vault of the vagina), infections of skin and soft tissues.
The pseudomembranous colitis (connected using antibiotics).
The gastritis or peptic ulcer of a 12-perstny gut connected with Helicobacter pylori.
Prevention of postoperative complications (especially interventions on a colon, okolorektalny area, appendectomy, gynecologic operations).

Route of administration and doses:

Intravenously, kapelno. Rate of administering - 5 ml/min.
At improvement of a condition of the patient it is necessary to transfer to oral administration of drug.
The infections caused by anaerobic microorganisms
Adults (with body weight about 70 kg) and children are more senior than 12 years:
The initial dose makes 15 mg/kg (3 ml).
The maintenance dose makes 7,5 mg/kg (1,5 ml) each 6 hours, within three days.
Then, in the same dose each 12 hours.
The maximum daily dose of metronidazole should not exceed 4 grams.
The average course of therapy makes 7-10 days, but for treatment of heavier infections the course of therapy can last 2-3 weeks.

Children up to 12 years:
The initial dose makes 7,5 mg/kg (1,5 ml), each 8 hours, within three days. Then, in the same dose, each 12 hours.
For the prevention of postoperative anaerobic complications Adults (with body weight about 70 kg) and children are more senior than 12 years:
Intravenously, kapelno 15 mg/kg (3 ml), within 30-60 minutes.
Administration of drug needs to be stopped in 1 hour prior to operation. In case of need, through 6-8 and even in 12-16 hours after operation it is possible to enter 7,5 mg/kg (1,5 ml) of drug.
Children up to 12 years:
The scheme of administration of drug is identical with above-stated, but the single intravenous dose makes 7,5 mg/kg (1,5 ml).
Use at a renal failure: the renal failure has no significant effect on pharmacokinetic indicators of drug therefore the dose of Klionum can be not changed. At the patients with heavy renal failures who are not on a hemodialysis at clearance of creatinine lower than 10 ml/min. a daily dose of drug should be reduced twice.

In case of simultaneous carrying out to the patient of a hemodialysis, it is necessary to remember reduction of an elimination half-life of metronidazole. Therefore, after carrying out a hemodialysis additional administration of drug can be required.
Hemodialysis: Metronidazole and its metabolites are well removed at a hemodialysis. As during a hemodialysis the elimination half-life sharply decreases (approximately till 3 o'clock), in certain cases, there can be a need additional administration of drug.
At a serious illness of a liver metronidazole is metabolized more slowly.
Thereof metronidazole and its metabolites can collect in a blood plasma. In these cases, the dose and intervals between administration of drug are established depending on severity of damage of a liver.
Elderly patients: at elderly patients the pharmacokinetics of metronidazole can change therefore there can be a need of control of concentration of metronidazole for blood serum.

Features of use:

Intravenous administration of solution for infusions is shown to patients at whom oral administration of drug is impossible. At multi-infections infusional Klionum can be applied in a combination with parenteral antibiotics, without mixing drugs among themselves.
At in drop introduction it is impossible to mix with other drugs.
When performing therapy of more than 10 days - only in reasonable cases, at strict observation of sick and regular control of laboratory indicators of blood. If longer course of therapy because of existence of chronic diseases is necessary, it is necessary to weigh carefully a ratio between the expected effect and potential risk of emergence of complications.
At use of drug the exacerbation of candidiasis can be observed.
The use of alcoholic drinks during a course of therapy is strictly forbidden.
At use of drug the insignificant leukopenia therefore it is reasonable to control a blood pattern (quantity of leukocytes) at the beginning and at the end of therapy can be observed.

Influence on ability to drive the car and occupation other types of activity demanding concentration of attention and speed of psychomotor reactions.
At emergence of side effects from the central nervous system it is necessary to refrain from control of cars and work with potentially dangerous mechanisms.

Side effects:

From a GIT: nausea, vomiting, appetite loss, colicy pains in the lower part of a stomach, diarrhea, a lock, a language oblozhennost, bitter, metal smack in a mouth, dryness in a mouth, a glossitis, pancreatitis.
From the hemopoietic system: reversible neutropenia (leukopenia).
From TsNS: peripheral neuropathy (feeling of numbness of extremities) seldom and only at prolonged use headaches, spasms, drowsiness, dizziness, an incoordination of movements, an ataxy, confusion of consciousness, a depression, hypererethism, weakness, sleeplessness, hallucinations meet.
Allergic reactions: skin rash, small tortoiseshell, skin itch, mnogoformny exudative erythema, Quincke's disease and anaphylactic reaction.
Local reakiiya: in an injection site thrombophlebitis is possible.
From gepatobiliarny system: increase in activity of liver enzymes, cholestasia, jaundice.
From urinogenital system: a dysuria, cystitis, a polyuria, an urine incontience, candidiasis, coloring of urine in red-brown color (causes a metronidazole metabolite, has no clinical value).
Others: fervescence, flattening of a tooth of T on the electrocardiogram.

Interaction with other medicines:

- Drug can strengthen effect of peroral anticoagulating drugs. The prothrombin time can increase therefore dose adjustment of peroral anticoagulants is necessary;
- 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.
- Inductors of enzymes of a microsomal oxidation in a liver (for example Phenytoinum, phenobarbital) can accelerate metronidazole elimination that will lead to decrease in its concentration in a blood plasma.
- Simultaneous alcohol intake causes reactions, similar to Disulfiramum (colicy pains in a stomach, nausea, vomiting, a headache, a dermahemia);
- Combined use with Disulfiramum is not admissible (the additive action, can cause confusion of consciousness);
- Concentration of lithium in blood can increase during a course of treatment metronidazole therefore before use Klionum it is necessary to lower a dose of lithium or to stop its reception for the period of treatment;
- Simultaneous administration of cyclosporine with metronidazole can lead to increase in concentration of cyclosporine in plasma that demands control of concentration of cyclosporine in a blood plasma;
- Metronidazole reduces clearance of a ftoruratsil in this connection its toxicity increases;
- At laboratory researches during administration of drug difficulties when determining activity of ALT, ACT, lactate dehydrogenase and concentration of triglycerides are possible;
- Simultaneous administration of drug with other solutions containing sodium salts can lead to a sodium delay in an organism.

Contraindications:

- the increased individual sensitivity to metronidazole or to other nitroimidazoles;
- pregnancy (I trimester), lactation period;
- 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).

WITH CARE
Pregnancy (II-III trimesters), renal/liver failure.

PREGNANCY AND PERIOD OF THE LACTATION
Pregnancy:
Metronidazole is contraindicated to use in the I trimester of pregnancy. Use of drug in II and III trimesters is possible only when the estimated advantage of therapy for mother exceeds potential risk for a fruit.
Feeding by a breast:
Drug gets into breast milk. In need of use of drug it is necessary to stop breastfeeding. During breastfeeding use of drug is contraindicated.

Overdose:

At emergence of symptoms of overdose (nausea, vomiting, an ataxy) symptomatic therapy as metronidazole has no specific antidote is carried out.
Metronidazole and its metabolites eliminirutsya well at a hemodialysis.

Storage conditions:

List B.
At a temperature from 15 to 30 °C, in the place protected from light.
To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

Solution for infusions of 5 mg/ml.
100 ml of solution in a colourless glass bottle for infusions (the I hydrolytic class). 1 bottle in a cardboard pack with the instruction on a medical use.