The instruction for medical use
of Klion® medicine
the Trade name
the International unlicensed
name Metronidazole Dosage Form Solution for infusions of 0.5% 100 ml
of 100 ml of solution contain
active agent – metronidazole of 500 mg
excipients: dihydrophosphate sodium a dihydrate, phosphate dinatrium dodecahydrate, sodium chloride, water for injections.
Colourless or slightly greenish color transparent solution
Other antibacterial drugs. Imidazole derivatives
the ATX J01X D01 Code
averages the Pharmacological Pharmacokinetics Elimination Half-life properties 8 hours. 60–80% of metronidazole and its metabolites are removed by kidneys, through intestines 6-15% of the entered dose are allocated.
Metronidazole quickly gets into cerebrospinal liquid, and reaches therapeutic concentration in abscess of a brain or lung. Metronidazole has the large volume of distribution and less, than 20% contact blood proteins. Metronidazole gets into bilious ways and reaches the same concentration, as in blood plasma.
Concentration of drug in blood plasma has linear dependence on the entered dose. The entered solution in a dose on 100-4000 mg (within eight hours) gave linearly increasing peak concentration in blood plasma. Disposable entered solution containing 500 mg of metronidazole gave concentration on average of 11.7-18 mkg/ml of plasma.
At patients with the broken hepatic function the decrease in clearance of metronidazole was noted.
Depression of function of kidneys has no significant effect on metronidazole pharmacokinetics.
Metronidazole gets to a microorganism by passive diffusion. In a bacterial cell it is restored and biologically active cytotoxic metabolite strikes DNA. Enzyme which restores nitrogroup of metronidazole, nitro-reductase, is inefficient in the presence of oxygen, the fact that metronidazole works only in anaerobic conditions is explained by it.
Metronidazole is effective at infection with some protozoa (Trichomonas vaginalis, Entamoeba hystolitica and Giardia lamblia) and obligate anaerobic microorganisms.
Spectrum of action:
In vitro is effective against all strict anaerobes (behind an exception Propionibaktery and Aktinomitsetov).
Gram-negative sticks: types of Bacteroides, including the Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron), types of Fusobacterium.
Gram-positive sticks: types of Clostridium, types of Eubacterium.
Gram-positive cocci: types of Peptococcus and Peptostreptococcus.
Drug is effective against some facultative anaerobes (Gardnerella vaginalis, Helicobacter pylori) and against some spirochetes.
– the severe forms of an infection caused by the anaerobic microorganisms sensitive to metronidazole (as a part of complex therapy)
– the multi-infections (caused by aerobic and anaerobic microorganisms)
– the infections caused by Bacteroides fragilis (resistant to clindamycin, chloramphenicol and penicillin)
– abdominal infections (peritonitis)
– gynecologic infections (abscess of a small pelvis, a parametritis, postnatal sepsis)
– infections of the central nervous system (the brain abscess caused by Bacteroides fragilis)
– lower respiratory tract infections (the gangrenous pneumonia caused by Bacteroides fragilis)
– infections of bones and joints (osteomyelitis)
– the sepsis and bacteremia caused by strains of Bacteroides fragilis or types of Clostridium
– prevention of postoperative complications, treatment of the infected postoperative wounds, especially at surgeries on digestive tract and bodies of a small pelvis.
A route of administration and doses
Intravenous administration of solution for infusions, is shown to patients at whom oral administration of drug is impossible. At improvement of a condition of the patient it is necessary to transfer to oral administration of drug.
In multi-infections of Klion®, solution for infusions, it is possible to apply in a combination with parenteral antibiotics, without mixing drugs at introduction among themselves.
At in in drop introduction of Klion® it is impossible to mix also with other drugs.
Speed of intravenous administration of solution for infusions: 5 ml a minute.
The infections caused by anaerobic microorganisms: the initial dose
for adults (body weight about 70 kg) and children is more senior than 12 years
makes 15 mg (3 ml) of Kliona® on body weight kg, a maintenance dose of-7.5 mg (1.5 ml) of Kliona® on body weight kg, each 6 hours, within three days, then in the same dose, each 12 hours.
The maximum daily dose of Kliona® should not exceed 4 g.
A course of treatment – 7-10 days, in case of a severe disease it is possible to increase a course up to 2-3 weeks.
Children up to 12 years: the initial dose makes 7.5 mg (1.5 ml) of Kliona® on body weight kg, each 8 hours, within three days, then in the same dose, each 12 hours.
Prevention of postoperative anaerobic complications: the adult (with body weight about 70 kg) and to children 12 years are more senior 15 mg (3 ml) of Kliona® on body weight kg, within 30-60 minutes are entered intravenously. Administration of drug needs to be finished in 1 hour prior to operation. In case of need, through 6-8 or in 12-16 hours after operation it is possible to enter repeatedly 7.5 mg (1.5 ml) of Kliona® on body weight kg.
Children up to 12 years:
The scheme of administration of drug same as at adults, but the single dose makes 7.5 mg (1.5 ml) of Kliona® on body weight kg.
In a renal failure: disturbance of renal function has no significant effect on pharmacokinetic indicators of drug therefore the dose of Kliona® can be not changed. However in case of simultaneous carrying out to the patient of a hemodialysis, it is necessary to remember shortening of elimination half-life of drug. In these cases, after carrying out a hemodialysis the additional administration of drug can be required. At
the patients who are not on a hemodialysis at clearance of creatinine lower than 10 ml/min. can collect metabolites of Kliona®. Carrying out a hemodialysis is recommended to such patients, peritoneal dialysis is inefficient.
Hemodialysis: Клион® and its metabolites are well removed at a hemodialysis. As during a hemodialysis the elimination half-life is sharply shortened (approximately till 3 o’clock), in certain cases, there can be a need of additional administration of drug.
In a serious illness of a liver: Клион® it metabolizutsya more slowly. Thereof drug and its metabolites can collect in blood plasma. In these cases, the dose and intervals between administration of drug are established depending on severity of damage of a liver.
Patients of advanced age: At this group of patients the pharmacokinetics of drug can change therefore there can be a need of control of level of metronidazole for blood serum.
Very often (≥1/10)
– a headache
Often (≥1/100 to & lt, 1/10)
– an abdominal pain, gripes in a stomach
Infrequently (≥1/1000 to & lt, 1/100)
– anorexia, vomiting, a language oblozhennost
– peripheral neuropathy (onemaniye of extremities), dizziness, an incoordination, drowsiness, a dysgeusia (metal smack)
– temperature increase, fever
– a dermahemia
– congestion of a nose
– an arthralgia
– flattening of a tooth of T on the ECG
– a dysuria, cystitis, a polyuria, urine incontinence, candidiasis
– a Quincke’s edema, an itching, rash, urticaria
Seldom (≥1/10000 to & lt, 1/1000)
– confusion of consciousness, an ataxy, irritability, a depression, hyperexcitability, weakness, insomnia, spasms, hallucinations, peripheral neuropathy
– a loss of appetite, constipations
– dryness of a mucous membrane, a glossitis, stomatitis
– darkening of urine
is Very rare (& lt, 1/10000)
– a neutropenia (leukopenia)
– anaphylactic reactions
– a cholestasia, jaundice
– a polymorphic erythema
– increase in activity of liver enzymes
These phenomena usually disappear with decrease in the entered dose or after end of a course of therapy.
– hypersensitivity to metronidazole, components of drug or other nitroimidazoles
– the first trimester of pregnancy, the lactation period
– organic lesions of central nervous system (including epilepsy)
– a heavy liver, renal failure
– Drug can strengthen effect of oral anticoagulating drugs. The prothrombin time can increase therefore dose adjustment of oral anticoagulants is necessary.
– Inductors of enzymes (e.g.: Phenytoinum, phenobarbital) can accelerate metronidazole removal that will lead to decrease in its level in plasma with simultaneous increase in clearance of Phenytoinum.
– Inhibitors of enzymes (e.g.: Cimetidinum) can increase semi-removal time, reduce clearance of metronidazole.
– Simultaneous alcohol intake causes the reactions similar to Disulfiramum (colicy pains in a stomach, nausea, vomiting, a headache, erubescence).
– Combined use with Disulfiramum is not admissible (additive action, can cause a psychotic state, confusion of consciousness).
– Lithium level in blood can increase during treatment by metronidazole therefore before use of Kliona® 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 level of cyclosporine in plasma that demands laboratory control (determination of level of cyclosporine in blood plasma).
– Metronidazole reduces clearance of a 5-ftoruratsil and as a result increases its toxicity.
– Drug can distort results of ALT, nuclear heating plant, a lactate dehydrogenase, glucose hexokinase and level of triglycerides in laboratory researches.
instructions Drug it is used for treatment in the conditions of a hospital.
When performing therapy more than 10 days (in reasonable cases), strict observation of the patient and regular laboratory
control is necessary. If at treatment of chronic diseases the long course of therapy is necessary, it is necessary to estimate a ratio between the expected effect and potential risk of development of side effects.
In liver diseases the removal of metronidazole slows down that can lead to drug accumulation. In this case drug dose adjustment is required. Patients with hepatic encephalopathy of Klion® should apply with care.
Simultaneous administration of drug with other solutions containing sodium salts can lead to a sodium delay in an organism.
At use of drug the exacerbation of candidiasis can be observed.
Consumption of alcoholic drinks during a course of therapy is strictly forbidden.
At use of drug the insignificant leukopenia can be observed therefore it is reasonable to control cellular composition of blood (quantity of leukocytes) at the beginning and at the end of therapy.
Drug is appointed with care the patient receiving corticosteroids or at predisposition to hypostases.
At simultaneous use of Klion® can increase lithium level in blood. In this regard, prior to the Klion® drug treatment, it is necessary to lower a dose of lithium or to stop its reception for the entire period of treatment by this drug.
Disturbance of renal function has no significant effect on pharmacokinetic indicators of drug therefore the dose of Kliona® can be not changed. However in case of simultaneous carrying out to the patient of a hemodialysis, it is necessary to remember shortening of elimination half-life of metronidazole. In such cases, after carrying out a hemodialysis the additional administration of drug can be required. At the patients who are not on a hemodialysis at clearance of creatinine lower than 10 ml/min. can collect metronidazole metabolites, in such cases carrying out a hemodialysis can be required, peritoneal dialysis is inefficient.
In need of simultaneous use of oral anticoagulants the correction of their dose is necessary.
Клион® it is necessary to apply with care in the presence of the acute and hard proceeding central nervous system diseases.
Metronidazole gets through a gemato-placental barrier.
Researches on pregnant women were not conducted, in II and III trimester of pregnancy drug is appointed only according to vital indications.
Metronidazole is found in maternal milk in the concentration equal to its concentration in plasma. It can give to milk bitter smack. In order to avoid negative effect of drug on the child, it is necessary to stop feeding by a breast for the period of treatment and in addition 1-2 days after its termination, or not to appoint drug, depending on that, performing this therapy is how necessary for mother.
Features of influence of medicine on ability to run the vehicle or potentially dangerous mechanisms
As drug is used for treatment in the conditions of a hospital, its influence on ability to run the vehicle or potentially dangerous mechanisms was not studied.
Symptoms: nausea, vomiting, ataxy.
Treatment: symptomatic therapy (gastric lavage, administration of activated carbon, carrying out a hemodialysis) as metronidazole has no specific antidote. Metronidazole and its metabolites eliminirutsya well at a hemodialysis.
The form of release and packing
On 100 ml of drug place in the bottles from colourless glass corked by a rubber bung, rolled by an aluminum cover and a plastic cover like “flip-off”.
On 1 bottle together with the instruction for medical use in the state and Russian languages place in a cardboard pack.
To Store storage conditions in the place protected from light at a temperature from 15 °C to 30 °C.
To store out of children’s reach!
After expiry date drug not to use a period of storage.
According to the prescription
Budapest JSC Gideon Richter Producer 1103, Dyomryoi St., 19-21, Hungary
the Owner of the registration certificate
of JSC Gideon Richter, Hungary
the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products:
Representative office of JSC Gideon Richter in RK
Phone number: 8-(7272)-58-26-22, 8-(7272)-58-26-23