Clion - instructions for use, dose, side effects, contraindications

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action is the biochemical reduction of the 5-nitro group of metronidazole by intracellular transport proteins of anaerobic microorganisms and protozoa. The reduced 5-nitro group of metronidazole reacts with the DNA of a cell of microorganisms, inhibiting the synthesis of their nucleic acids, which leads to the death of bacteria.

Active with respect to Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, as well as obligate anaerobes Bacteroides spp. (incl. 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.). The MIC for these strains is 0.125-6.25 μg / ml.

In combination with amoxicillin shows activity against Helicobacter pylori (amoxicillin suppresses the development of resistance to metronidazole).

Metronidazole is insensitive Aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional aerobes.

Increases the sensitivity of tumors to radiation, causes disulfiram-like reactions, stimulates reparative processes.

Pharmacokinetics:

Distribution: It has a high penetrating ability, reaching bactericidal concentrations in most tissues and body fluids, including lungs, kidneys, liver, skin, cerebrospinal fluid, brain, bile, saliva, amniotic fluid, abscess cavities, vaginal secretion, seminal fluid, breast milk, penetrates the blood-brain barrier (BBB) and the placental barrier.

The volume of distribution: adults - about 0.55 l / kg, newborns 0.54-0.81 l / kg. The stan is 6 to 40 μg / ml, depending on the dose. The connection with plasma proteins is 10-20%. With iv injection of 500 mg for 20 min C_mOh in the blood serum after 1 hour - 35.2 μg / ml. The concentration of metronidazole in the serum after 4 hours was 33.9 μg / ml, after 8 hours - 25.7 μg / ml; C_min with subsequent administration of 18 μg / ml. TS_mOh - 30-60 minutes, the therapeutic concentration persists for 6-8 hours. With normal bile formation, the concentration of metronidazole in the bile after IV introduction can significantly exceed the concentration in the plasma.

Biotransformation: In the body, about 30-60% of metronidazole is metabolized by hydroxylation, oxidation and glucuronation. The main metabolite (2-oxymetronidazole) also has antiprotozoal and antimicrobial effects.

Excretion: The half-life (T_1/2) with normal liver function - 8 hours (6 to 12 hours), with alcohol damage of the liver - 18 hours (from 10 to 29 hours), in newborns born at term of pregnancy - 28-30 weeks - about 75 hours, 32- 35 weeks, 35 hours, 36-40 weeks - 25 hours. It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%.

In severe renal impairment (creatinine clearance less than 10 ml / min) in patients after repeated administration, cumulation of metronidazole in serum can be observed, and therefore the dose of the drug should be reduced in half.

Metronidazole and major metabolites are rapidly removed from the blood during hemodialysis (T_1/2 is reduced to 2.6 hours). When peritoneal dialysis is withdrawn in small quantities.

Indications:

Protozoal infections: extra-intestinal amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis, balantidiasis, giardiasis, cutaneous leishmaniasis, trichomonas vaginitis, trichomoniasis urethritis.

Infections caused by Bacteroides spp. (incl. Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus): infection of bones and joints, infections of the central nervous system, incl. meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis.

Infections caused by the species Clostridium spp., Peptococcus and Peptostreptococcus: infection of the abdominal cavity (peritonitis, liver abscess), pelvic infection (endometritis, abscess of fallopian tubes and ovaries, vaginal vaginal infection), skin and soft tissue infections.

Pseudomembranous colitis (associated with the use of antibiotics).

Gastritis or duodenal ulcer associated with Helicobacter pylori.

Prevention of postoperative complications (especially interference on the colon, near-rectal area, appendectomy, gynecological operations).

Contraindications:

- Increased individual sensitivity to metronidazole or other nitroimidazoles;

- Pregnancy (I trimester), lactation period;

- Lakopenia (including in the anamnesis);

- organic lesions of the central nervous system (including epilepsy);

- Hepatic insufficiency (in case of the appointment of large doses).

Carefully:

Pregnancy (II-III trimesters), renal / hepatic insufficiency.

Pregnancy and lactation:

Pregnancy

Metronidazole is contraindicated in the first trimester of pregnancy. Application of the drug in II and III trimester is possible only in cases where the intended benefit of therapy for the mother exceeds the potential risk to the fetus.

Lactation

The drug penetrates into breast milk. If you need to use the drug should stop breastfeeding. During the period of breastfeeding, the use of the drug is contraindicated.

Dosing and Administration:

Intravenously, drip. The rate of administration is 5 ml / min.

When the patient's condition improves, it should be transferred to the oral administration of the drug.

Infections caused by anaerobic microorganisms

Adults (with a body weight of about 70 kg) and children over 12 years of age:

The initial dose is 15 mg / kg (3 ml).

The maintenance dose is 7.5 mg / kg (1.5 ml) every 6 hours for three days.Then, in the same dose every 12 hours.

The maximum daily dose of metronidazole should not exceed 4 grams.

The average course of therapy is 7-10 days, but for treatment of more serious infections, the course of therapy can last 2-3 weeks.

Children under 12 years:

The initial dose is 7.5 mg / kg (1.5 ml), every 8 hours, for three days. Then, in the same dose, every 12 hours.

To prevent postoperative anaerobic complications

Adults (with a body weight of about 70 kg) and children over 12 years of age:

Intravenously, drip 15 mg / kg (3 ml), for 30-60 minutes.

The drug should be discontinued 1 hour before the operation. If necessary, after 6-8 and even 12-16 hours after the operation, 7.5 mg / kg (1.5 ml) of the drug can be administered.

Children under 12 years:

The scheme of administration of the drug is the same as above, but a single intravenous dose is 7.5 mg / kg (1.5 ml).

Application for renal dysfunction: the renal dysfunction does not have a significant effect on the pharmacokinetic parameters of the drug, so the dose of Clion can not be changed. In patients with severe impairment of renal function not on hemodialysis, when creatinine clearance is less than 10 ml / min. The daily dose of the drug should be reduced by 2 times.

In the case of simultaneous hemodialysis, it is necessary to remember the decrease in the half-life of metronidazole. Therefore, after hemodialysis may require additional administration of the drug.

Hemodialysis: Metronidazole and its metabolites are well excreted in hemodialysis. Since during hemodialysis, the elimination half-life decreases dramatically (up to about 3 hours), in some cases, it may be necessary to administer the drug additionally.

With severe liver disease metronidazole it is metabolized more slowly. Consequently metronidazole and its metabolites can accumulate in the blood plasma. In these cases, the dose and intervals between administration of the drug are determined depending on the severity of the liver damage.

Elderly patients: in elderly patients, the pharmacokinetics of metronidazole may change, so it may be necessary to monitor the concentration of metronidazole in the blood serum.

Side effects:

From the gastrointestinal tract: nausea, vomiting, loss of appetite, cramping pains in the lower abdomen, diarrhea, constipation, tongue lagging, bitter, metallic taste in the mouth, dry mouth,glossitis, pancreatitis.

From the hematopoietic system: reversible neutropenia (leukopenia).

From the side of the central nervous system: peripheral neuropathy (feeling of numbness of the extremities) is rare and only with prolonged use there are headaches, cramps, drowsiness, dizziness, impaired coordination of movements, ataxia, confusion, depression, increased excitability, weakness, insomnia, hallucinations.

Allergic reactions: skin rash, hives, itchy skin, multiform erythema exudative, angioedema and anaphylactic reaction.

Local Reactions: Thrombophlebitis is possible at the site of administration.

From the hepatobiliary system: increased activity of hepatic enzymes, cholestasis, jaundice.

From the genitourinary system: dcystitis, polyuria, urinary incontinence, candidiasis, staining of urine in red-brown color (causes metronidazole metabolite, has no clinical significance).

Other: increase in body temperature, flattening of the T wave on the electrocardiogram.

Overdose:

When symptoms of an overdose (nausea, vomiting, ataxia) are symptomatic, since metronidazole does not have a specific antidote. Metronidazole and its metabolites are well eliminated in hemodialysis.

Interaction:

- The drug may enhance the effect of oral anticoagulant drugs. Prothrombin time may increase, so a dose adjustment of oral anticoagulants is necessary;

- Cimetidine inhibits the metabolism of metronidazole, which can lead to an increase in its concentration in the blood serum and an increased risk of side effects.

- Inductors of microsomal oxidation enzymes in the liver (for example phenytoin, phenobarbital) can accelerate the elimination of metronidazole, which will lead to a decrease in its concentration in the blood plasma.

- Simultaneous use of alcohol causes reactions like disulfiram (cramping abdominal pain, nausea, vomiting, headache, skin hyperemia);

- Inadmissible joint application with disulfiram (additive effect, can cause confusion);

- The concentration of lithium in the blood can increase during the course of treatment with metronidazole, so before starting to use Clion, you need to reduce the dose of lithium or stop taking it for the duration of treatment;

- Simultaneous administration of cyclosporine with metronidazole may lead to an increase in the concentration of cyclosporine in the plasma, which requires the control of the concentration of cyclosporine in the blood plasma;

- Metronidazole reduces the clearance of fluorouracil, in connection with which its toxicity increases;

- At laboratory researches during reception of a preparation there are difficulties at definition of activity ALT, ACT, lactate dehydrogenase and triglyceride concentrations;

- Simultaneous administration of the drug with other solutions containing sodium salts can lead to sodium retention in the body.

Special instructions:

Intravenous administration of a solution for infusion is indicated to patients who are unable to receive oral medication.

With mixed infections, the infusion Clion can be used in combination with parenteral antibiotics, without mixing drugs with each other.

When i / v drip introduction can not be mixed with other drugs.

When carrying out therapy for more than 10 days - only in justified cases, with strict supervision of the patient and regular monitoring of laboratory blood counts.

If a longer course of therapy is required due to the presence of chronic diseases,you should carefully weigh the relationship between the expected effect and the potential risk of complications.

When using the drug, there may be an exacerbation of candidiasis.

The use of alcoholic beverages during the course of therapy is strictly prohibited.

When using the drug, minor leukopenia can be observed, so it is advisable to monitor the blood picture (the number of white blood cells) at the beginning and at the end of therapy.

Effect on the ability to drive transp. cf. and fur:

When there are side effects from the central nervous system, one should refrain from controlling cars and working with potentially dangerous mechanisms.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

100 ml of solution in a colorless glass vial for infusions (hydrolytic class I).

1 bottle in a cardboard box with instructions for medical use.

Storage conditions:

At a temperature of 15 to 30 ° C, in a place protected from light.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N015200 / 01

Date of registration:16.07.2009

Expiration Date:Unlimited

The owner of the registration certificate:GEDEON RICHTER, OJSC GEDEON RICHTER, OJSC Hungary

Manufacturer: & nbsp

GEDEON RICHTER, Ltd. Hungary

Representation: & nbspGEDEON RICHTER OJSC GEDEON RICHTER OJSC Hungary

Information update date: & nbsp29.01.2018

Illustrated instructions

Instructions

Clion (Klion)