Metronidazol-Darnitsa solution for inf. 5mg/ml fl. 100 ml

Pharmacological properties

Pharmacodynamics

Active ingredient of medicine — metronidazole — belongs to group of derivatives of a nitroimidazole. metronidazole is capable to get into microorganisms and in anaerobic conditions forms with microbic nitrozoradikala pyruvate-feredoksinoksidoreduktazoy by oxidation of a feredoksin and a flavodoksin. nitrozoradikala form accession products with the main vapors of DNA that leads to a rupture of chains of DNA and death of microbic cages.

Minimum Inhibiting Concentration (MIC) of metronidazole is established to

by the European committee on testing of antimicrobic sensitivity, an interruption point, the separating sensitive organisms (S) from resistant (R), following:

• gram-positive anaerobe bacterias (S of ≤4 mg/ml, R 4 mg/ml);
• gram-negative anaerobe bacterias (S of ≤4 mg/ml, R 4 mg/ml).

List of sensitive and resistant microorganisms (according to Central office for the analysis of data on resistance of antibiotics of systemic action, Germany, December, 2009):

Sensitive types

Anaerobe bacterias: Bacteroides fragilis, Clostridium difficile °, Clostridium perfringens ° ^∆ , Fusobacterium spp. °, Peptoniphilus spp. °, Peptostreptococcus spp. °, Porphyromonas spp. °, Prevotella spp., Veillonella spp. °

Other microorganisms: Entamoeba histolytica, Gardnerella vaginalis °, Giardia lamblia °, Trichomonas vaginalis. °

Types for which the acquired sensitivity can be a problem

Gram-negative aerobes: Helicobacter pylori.

Vrozhdennorezistentny types (all obligate aerobes)

Gram-positive aerobes: Enterococcus spp., Staphylococcus spp., Streptococcus spp.

Gram-negative aerobes: Enterobacteriaceae, Haemophilus spp.

a °n time of the publication of this information of available data did not exist. In primary literature possible standard reference references and therapeutic recommendations about sensitivity of the corresponding types are given.

^Δ Can be applied only to patients with an allergy to penicillin.

Pharmacokinetics

Later in/in introductions metronidazole is widely metabolized by

in body tissues. Linking with proteins of blood plasma makes less than 20%, the visible volume of distribution — 36 l. It appears in the majority of fabrics and liquids of an organism, including bile, bones, cerebral abscess, cerebrospinal fluid, a liver, saliva, semen and discharges from a vagina where the concentration close to concentration in blood plasma are reached. Also gets through a placenta and into breast milk in the concentration equivalent to concentration in blood plasma.

Metronidazole is metabolized by

in a liver by oxidation of side chains and formation of a glucuronide. Its metabolites include a product of acid oxidation, hydroxylic derivative and the Glucuronide. The main metabolite in blood plasma — a hydroxylated metabolite, and the main metabolite in urine — acid.

About 80% of metronidazole is allocated with kidneys, from them to 10% — in not changed look. A small amount of metronidazole is distinguished through a liver. The t _½ makes 8 (6–10) h

Renal failure discharge only slightly detains.

In a serious illness of a liver should expect decrease in clearance and lengthening of T _½ from blood (to 30 h).

Indication

Treatment and prevention of the infections caused by the microorganisms sensitive to metronidazole (generally anaerobic bacteria): central nervous system infections (including brain abscess, meningitis); infections of lungs and a pleura (including necrotic pneumonia, aspiration pneumonia, abscess of lungs); endocarditis; infections of a digestive tract and an abdominal cavity (including peritonitis, abscess of a liver, an infection after operations on thick or a rectum, purulent damages of an abdominal or pelvic cavity); gynecologic infections (including an endometritis after a hysterectomy or Cesarean section, patrimonial fever, septic abortion); infections of ENT organs and an oral cavity (including a tonsillitis simanovsky — the plaut — Vincenta); infections of bones and joints (including osteomyelitis); gas gangrene; a septicaemia with thrombophlebitis.

Preventive application is always shown to

before operations with high risk of mephitic gangrenes (before gynecologic and intraabdominal operations).

At the mixed aerobic and mephitic gangrenes should apply in addition corresponding antibiotics to treatment of aerobic infections.

At use of metronidazole should consider national and international recommendations about appropriate use of germicides.

Use

Drug is used in the form of slow in/in infusion (that is no more than 100 ml within not less than 20 min., usually during 1 h).

Drug can be parted with

before introduction, adding other medicines or solutions for cultivation, such as 0.9% chloride sodium solution for injections or 5% glucose solution for infusions.

Antibiotics appointed at the same time should be entered separately.

Dose should be skorrigirovat according to individual reaction of the patient to treatment, age and body weight and also type and disease severity.

Should follow the following rules on a medicine dosage.

Treatment

to Adults and children is aged more senior than 12 years. The usual dose makes 500 mg each 8 h. In the presence of medical indications in an initiation of treatment it is possible to appoint a load dose of 15 mg/kg of body weight.

Children aged from 2 up to 12 years. The usual dose makes 7–10 mg/kg of body weight each 8 h that corresponds to a daily dose of 20-30 mg/kg of body weight.

to Patients with a renal failure. There is no need for medicine dose adjustment (see. Pharmacological PROPERTIES).

to Patients with a liver failure. Dose adjustment of medicine because of lengthening of its T _½ and decrease in clearance can be required by persons with a heavy liver failure (see. Pharmacological PROPERTIES).

Duration of treatment depends on efficiency. In most cases the 7-day course will be sufficient. In the presence of clinical indications the treatment can be continued (see. Special INSTRUCTIONS).

Before - and postoperative prevention

to Adults and children is aged more senior than 11 years. The usual dose makes 500 mg. Administration of metronidazole is finished approximately for 1 h before operation. To administer the medicament repeatedly in the same dose in 8 and 16 h

to Children aged from 2 to 11 years. The usual dose makes 15 mg/kg of body weight. Administration of metronidazole is finished approximately for 1 h before operation. To administer the medicament repeatedly in a dose of 7.5 mg/kg of body weight in 8 and 16 h

Contraindication

Hypersensitivity to metronidazole, other nitroimidazolny derivatives or other components of medicine.

Side effects

Infection and invasion: the genital superinfections (caused by candida), pseudomembranous colitis which can arise in time or after therapy and is shown in the form of heavy persistent diarrhea.

Detailed description of urgent treatment is provided by

in the section SPECIAL INSTRUCTIONS.

from blood and lymphatic system: leukopenia, granulocytopenia, thrombocytopenia, Agranulocytosis, aplastic anemia.

during prolonged use of medicine should carry out by

regular control of a blood count surely.

from mentality: a condition of confusion of consciousness, irritability, a depression, psychotic frustration, including hallucinations.

from nervous system: a headache, dizziness, drowsiness or insomnia, spasms, peripheral neuropathy (which symptoms are paresthesias, pain, heavy feeling and prickings in extremities), encephalopathy, development of a subacute cerebellar syndrome (which symptoms are the ataxy, a dysarthtia, violation of gait, a nystagmus, a tremor).

At appearance of spasms or symptoms of peripheral neuropathy should be told the doctor immediately.

from an organ of sight: a disorder of vision, doubling in eyes, short-sightedness, okulogirny crisis (separate cases).

from a cardiovascular system: changes on the ECGs similar to alignment of a tooth of T.

from digestive system: nausea, vomiting, diarrhea, a glossitis and stomatitis, an eructation with bitter taste, heavy feeling in epigastric area, loss of appetite, metal smack in a mouth, a coated tongue, pancreatitis (separate cases).

from a gepatobiliarny system: gepatobiliarny violations, abnormal values of liver enzymes and bilirubin, hepatitis, jaundice.

from the musculoskeletal system and connective tissue: arthralgia, myalgia.

from an urinary system: dark color of urine (because of metronidazole metabolite discharge), a dysuria, cystitis and incontinence of urine.

from the immune system, leather and hypodermic cellulose: reactions of hypersensitivity of easy and average degree, including skin reactions (itch, urticaria, a multiformny erythema), a Quincke's disease, medicinal fever, heavy system reactions of hypersensitivity (an anaphylaxis up to an acute anaphylaxis), Stephens's syndrome — Johnson (separate messages), a Lyell's disease (separate messages).

Heavy reactions, such as Stephens's syndrome — Johnson and a Lyell's disease, demand immediate therapeutic intervention.

General violations and violations in the injection site: irritation of veins (up to thrombophlebitis) later in/in introductions, pustulous rash, weakness.

Special instructions

to Patients with severe damages of a liver, violation of a hematopoiesis (including a granulocytopenia), with active or chronic heavy disorders of peripheral nervous system or central nervous system to use medicament only in case the expected advantage exceeds potential risk.

At use of medicine the development of convulsive attacks and peripheral neuropathy which was characterized by numbness or paresthesia of extremities is possible

. In case of appearance of neurologic pathology it is necessary to carry out the urgent assessment of a ratio advantage/risk for therapy continuation by metronidazole.

Drug treatment can be followed by emergence of heavy reactions of hypersensitivity (including an acute anaphylaxis). In case of development of such reactions it is necessary to stop use of medicine and to begin the general emergency treatment.

Long therapy by metronidazole can lead

to disturbance of a hematopoiesis because of oppression of function of marrow. Its manifestations are given in the section SIDE EFFECTS. At prolonged use of medicine it is necessary to control a blood count carefully.

Heavy persistent diarrhea which development is possible at treatment or within the next weeks can be a consequence of pseudomembranous colitis (in many cases of the caused Clostridium difficile) (see. Side EFFECTS). This disease of intestines caused by antibiotics can threaten life and demands immediate treatment. During medicament treatment it is not necessary to apply the medicines suppressing an intestines vermicular movement.

Long therapy by metronidazole can lead

to disturbance of a hematopoiesis in view of oppression of marrow. Its manifestations are given in the section SIDE EFFECTS. During prolonged use of medicine it is necessary to control a blood count carefully.

Duration of medicament treatment or the medicines containing other derivatives of a nitroimidazole should not exceed

10 days. Only in special cases if necessary the period of treatment can be prolonged accompanied by the corresponding clinical and laboratory monitoring. Repeated therapy should be limited as much as possible prior to special cases. It is necessary to adhere accurately to these restrictions as the possible mutagen activity of metronidazole cannot exclude because of increase in frequency of development of certain tumors that was recorded in researches on animals.

Metronidazole can affect results euzymatic - spectrophotometric definition of AsAT, AlAT, LDG, TG and a glyukozohexokinaza, reducing their values (perhaps, to zero).

Metronidazole can influence definition of liver enzymes at measurement by NADH method of the constant stream based on definition of a final point of decrease in the restored NADH. Unusually low concentration of liver enzymes, including zero values can be noted.

Drug is suitable

only for single application. To destroy the unused remains.

Drug can be parted with

in 0.9% solution of sodium of chloride or 5% glucose solution. During the procedure of cultivation it is necessary to adhere to usual measures of an asepsis.

Solution should be applied, only if it transparent, and the container or packing have no visible signs of damage.

Use during pregnancy and feeding by a breast. Safety of use of metronidazole during pregnancy is studied insufficiently. In particular, messages about its application are contradictory. Some researches revealed increase in frequency of malformations. In researches on animals teratogenic effects of metronidazole are not revealed.

In the I trimester of pregnancy should apply metronidazole only to treatment of heavy infections, life-threatening, in the absence of safer alternative. In II and III trimester metronidazole can be applied to treatment of other infections if the expected advantage for mother obviously exceeds possible risk for a fruit.

As metronidazole gets into breast milk, during treatment it is necessary to stop feeding by a breast. Feeding should be resumed not earlier than in 2–3 days after the end of therapy as metronidazole has extended with T _½ .

Children. Drug is used at children aged from 2 years.

Ability to influence speed of response at control of vehicles or other mechanisms. Drug is capable to influence speed of response at control of vehicles or other mechanisms. This influence is generally shown in an initiation of treatment.

At simultaneous application with other medicines such interactions are possible

Interaction:

with Amiodaronum — it was reported about lengthening of an interval of Q-T and torsade de pointes; at simultaneous use of medicines the monitoring of an interval of Q-T on the ECG, and in case of symptoms which can indicate torsade de pointes, such as dizziness, cardiopalmus or loss of consciousness is recommended — to see a doctor;

with barbiturates — strengthening of hepatic metabolism of metronidazole and decrease in its T _½ from blood plasma up to 3 h;

with busulfany, carbamazepine, lithium, takrolimusy, fluorouratsily, cyclosporine — increase in concentration of the last in blood plasma (in case of a takrolimus — it is possible, because of suppression of his hepatic metabolism) at simultaneous use of metronidazole it is necessary to be careful with lithium, with takrolimusy or cyclosporine — to carry out monitoring of their concentration in blood plasma and function of kidneys and in case of need to korrigirovat a dosage; it is necessary to avoid application of a combination of metronidazole with busulfany because of potential risk of heavy toxicity and a lethal outcome;

with Disulfiramum — a condition of confusion of consciousness or even psychotic reactions; it is necessary to avoid application of this combination of medicines;

with contraceptives — some antibiotics in some cases can reduce efficiency of oral contraceptives, influencing bacterial hydrolysis of steroid conjugates in intestines and thus reducing repeated absorption of not conjugated steroids therefore concentration of active steroids in blood plasma decrease. This unusual interaction is possible at women with the high level of discharge of steroid conjugates with bile. The known cases of inefficiency of oral contraceptives are connected with application of various antibiotics, including ampicillin, amoxicillin, tetracycline and also metronidazole;

from the mikofenolat mofetily — decrease in oral bioavailability; at simultaneous use of medicines the careful clinical and laboratory monitoring for identification of reduction of immunosuppressive effect of mikofenolovy acid is recommended;

with coumarin derivatives — strengthening of anticoagulating effect of derivatives of coumarin and increase in risk of developing of bleeding owing to decrease in degradation in a liver; at simultaneous use of medicines the dose adjustment of anticoagulants can be required;

with Phenytoinum — oppression of hepatic metabolism of Phenytoinum and decrease in its concentration in blood plasma and also decrease in efficiency of metronidazole;

with Cimetidinum — increase in concentration in metronidazole blood plasma because of reduction of its removal.

during therapy by metronidazole should avoid consumption of alcoholic beverages because of a possibility of development of side reactions, such as dizziness and nausea (disulfiramopodobny effect).

Overdose

Symptoms: development of the above side reactions.

Treatment: if necessary metronidazole can be removed effectively by a hemodialysis. There is no specific treatment or antidote.

Storage conditions

In original packing at a temperature not above 25 °C not to freeze

.