Metronidazole of 0,5%

General characteristics. Structure:

Active ingredient: 500 mg of metronidazole in 100 ml of solution.
 
Excipients: sodium phosphate monosubstituted, sodium citrate disubstituted, sodium chloride, water for injections.
 
Antibacterial, antiprotozoan (trikhomonatsidny), antiulcerous agent.

Pharmacological properties:

Pharmacodynamics. Drug shows high activity concerning Trichomonas vaginalis, Giardia intestinalis, Entamoeba histolytica, Lamblia intestinalis, and also concerning strict anaerobes (sporo-and asporous) - Bacteroides spp. (B.fragilis, B.ovatus, B.distasonis, B.thetaiotaomicron, B.vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains of Eubacterium.

Aerobic microorganisms and facultative anaerobes, but in the presence of the mixed flora are not sensitive to metronidazole (aerobes and anaerobe bacterias) metronidazole works synergy with antibiotics, effective against usual aerobes.

The mechanism of effect of metronidazole 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.

Pharmacokinetics. Absorption. After intravenous administration in a dose of 500 mg within 20 min. Cmax in blood serum in 1 h makes 35.2 mkg/ml, in 4 h – 33.9 mkg/ml, in 8 h – 25.7 mkg/ml; Cmin at the subsequent introduction – 18 mkg/ml. At in introduction of Cmax it is reached in 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.

Distribution. Linkng with proteins of plasma – 10-20%. Vd adults – 0.55 l/kg, at newborns have 0.54-0.81 l/kg. Metronidazole has high penetration. Reaches bactericidal concentration in lungs, kidneys, a liver, a brain, skin, cerebrospinal fluid, bile, saliva, amniotic liquid, a cavity of abscesses, a vaginal secret, semen, breast milk. Gets through GEB, passes through a placental barrier.

Metabolism. It is metabolized (about 30-60%) by a hydroxylation, oxidation and a glyukuronirovaniye. The main metabolite – the 2nd oxymetronidazole – has antiprotozoan and antimicrobic effect.

Removal. 20% - in not changed look are removed by kidneys (60-80%); through intestines 6-15% are removed. T1/2 is 8 h (6-12 h). Renal clearance – 10.2 ml/min.

Pharmacokinetics in special clinical cases. At alcoholic damage of a liver of T1/2 makes 18 h (10-29 h), at the newborns who were born at duration of gestation of 28-30 weeks – 75 h, at the term of 32-35 weeks – 35 h, at the term of 36-40 weeks – 25 h.

At patients with a renal failure after repeated introduction cumulation of metronidazole in blood serum can be observed.

Indications to use:

Protozoan infections: an abenteric amebiasis, including amoebic abscess of a liver, an intestinal amebiasis, trichomoniasis, гиардиазис, a balanthidiasis, a lambliasis, 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, TsNS infections (including meningitis, brain abscess), bacterial endocarditis, pneumonia, empyema and abscess of lungs;

The infections caused by Bacteroides spp. (including Bacteroides fragilis), Clostridium spp., Peptococcus spp., Peptostreptococcus spp.: infections of an abdominal cavity (peritonitis, liver abscess), infections of bodies of a small pelvis (an endometritis, an endomyometritis, abscess of fallopian pipes and ovaries, infections of a vault of the vagina after surgeries), infections of skin and soft tissues;

The sepsis caused by Bacteroides spp. (Wh. Bacteroides fragilis) iclostridium spp.;

Prevention of postoperative complications (especially interventions on a colon, okolorektalny area, appendectomy, gynecologic operations);

Combination therapy of the heavy mixed aerobic-anaerobic infections.

Route of administration and doses:

Solution is entered intravenously, kapelno, with a speed of 5 ml a minute.

Solution can be entered in an undiluted look or to part 300-400 ml of normal saline solution.

To adults and children 12 years at anaerobic infections are more senior – to 500 mg there are each 8 hours within 7-10 days, in hard cases – 2-3 weeks. The maximum daily dose – 4 g.

For prevention anaerobic инфекцииперед planned operation on pelvic bodies and urinary tract to adults and children 12 years are more senior metronidazolnaznachat in the form of infusions in a dose 500-1000 mg, in day of operation and next day - in a dose of 1500 mg/days (on 500 mg each 8 hours). In 1-2 days usually pass to a maintenance therapy with peroral forms of metronidazole.

To children up to 12 years: 7,5 mg/kg of body weight (1,5 ml/kg) each 8 hours with a speed of 5 ml a minute.

For patients with the expressed renal failures (KK less than 30 ml/min.) and/or a liver a daily dose of metronidazole to 1000 mg; (frequency rate of reception 2 times).

Features of use:

With care appoint at diseases of kidneys, a liver, the central and peripheral nervous system.

During administration of drug it is impossible to take alcohol, so kakmetronidazolobladat ability to cause disgust for alcoholic drinks. Long administration of drug should be carried out under control of indicators of peripheral blood.

Pregnancy and lactation. Metronidazole is contraindicated to use in the I trimester of pregnancy. In II and III trimesters of pregnancy drug is used only according to vital indications.

Metronidazole is emitted with breast milk. In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Side effects:

From digestive tract: nausea, vomiting, diarrhea, lack of appetite, unpleasant metal smack in a mouth, epigastric pains, pancreatitis;

From the central nervous system: headache, dizziness, hyperexcitability, depressions, sleep disorder, weakness; in some cases – confusion of consciousness, a hallucination, spasm, an ataxy, a lack of coordination of movements;

From a peripheral nervous system: peripheral neuropathy;

From urinogenital system: a dysuria, cystitis, a polyuria, an urine incontience, coloring of urine in red-brown color, a burning sensation in an urethra;

Overdevelopment of fungal flora of a vagina and oral cavities (candidiases);

Allergic reactions: skin rash, itch, small tortoiseshell, dermahemia, nose congestion, fever, arthralgia;

From the hemopoietic system: tranzitorny leukopenia and thrombocytopenia; the marrow aplasia case is described.

Interaction with other medicines:

Metronidazoldlya it is not recommended to mix intravenous injections with other medicines.

Priprimeneniya of metronidazole should be careful at co-administration with some medicines:

Warfarin and other indirect anticoagulants. Metronidazole strengthens effect of indirect anticoagulants that leads to increase in time of formation of a prothrombin.

Disulfiramum (эспераль). Simultaneous use can lead to development of various neurologic symptoms therefore it is not necessary to appoint metronidazole sick which accepted Disulfiramum within the last two weeks.

Tsimetidiningibiruyet 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.

Antimicrobic the deystviyemetronidazola amplifies in a combination with streptocides and antibiotics.

Contraindications:

Hypersensitivity to metronidazole or other nitroimidazolny derivatives;

Organic lesions of TsNS;

Blood diseases (leukopenia, thrombocytopenia, anemia);

Epilepsy;

Liver failure (at use of drug in high doses);

I trimester of pregnancy,

Lactation (breastfeeding);

Pregnancy and lactation
 
Metronidazole is contraindicated to use in the I trimester of pregnancy. In II and III trimesters of pregnancy drug is used only according to vital indications.
 
Metronidazole is emitted with breast milk. In need of use of drug in the period of a lactation it is necessary to resolve an issue of the breastfeeding termination.

Overdose:

Symptoms: nausea, vomiting, an ataxy, in hard cases - peripheral neuropathy and epileptic seizures.

Treatment: symptomatic; the specific antidote is absent.

Storage conditions:

In the dry, protected from light place at a temperature not above + 25 °C. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

Solution for infusions on 100 ml in polymeric containers.