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

Active substance:
Metronidazole	5.0 mg
Excipients:
Sodium chloride	7.9 mg
Sodium hydrogen phosphate	0.476 mg
Citric acid monohydrate	0.229 mg
Water for injections	up to 1 ml

Theoretical osmolarity - 299.28 mOsm / l

Description:

Transparent solution from colorless to light yellow color.

Pharmacotherapeutic group:antimicrobial and antiprotozoal agent

ATX: & nbsp

P.01.A.B Nitroimidazole derivatives

P.01.A.B.01 Metronidazole

Pharmacodynamics:

Antiprotozoal and antimicrobial drug, a derivative of 5-nitroimidazole. The mechanism of action of metronidazole 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.

The drug shows a high activity in a relationship Trichomonas vaginalis, Giardia intestinalis (Lamblia intestinalis), Entamoeba histolytica, as well as in respect of obligate anaerobes (sporo- and non-spore-forming) Bacteroides spp. (AT. fragilis, AT. ovatus, AT. distasonis, AT. thetaiotaomicron, AT. vulgatus), Fusobacterium spp., Clostridium spp., Peptostreptococcus spp., Peptococcus spp., sensitive strains Eubacterium.

To Metronidazole not sensitive Aerobic microorganisms and facultative anaerobes, but in the presence of mixed flora (aerobes and anaerobes) metronidazole acts synergistically with antibiotics effective against conventional anaerobes.

Pharmacokinetics:

Distribution: the drug 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 through the blood-brain and placental barrier.

The volume of distribution: adults - about 0.55 l / kg, newborns - 0.54-0.81 l / kg. The connection with plasma proteins is 10-20%.

With the intravenous administration of 500 mg of metronidazole for 20 minutes to patients with anaerobic infection, the serum concentration of the drug in an hour was 35.2 μg / ml, after 4 hours - 33.9 μg / ml, after 8 hours - 25.7 μg / ml . With normal bile formation, the concentration of metronidazole in the bile after intravenous administration may significantly exceed the concentration of metronidazole in the blood plasma.

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

Excretion: half-life (T_1/2) with normal liver function - 8 hours (from 6 to 12 hours), with alcoholic liver damage - 18 hours (from 10 to 29 hours), in newborns born at the gestation period of 28-30 weeks - about 75 hours, 32-35 weeks - 35 h, 36-40 weeks - 25 h. It is excreted by the kidneys 60-80% (20% unchanged), through the intestine - 6-15%. The renal clearance is 10.2 ml / min. In patients with impaired renal function after repeated administration of the drug cumulation of metronidazole in serum can be observed. Therefore, in patients with severe renal failure, the frequency of metronidazole should be reduced.

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

Indications:

Metronidazole is recommended for the treatment of infections caused by microorganisms that are sensitive to the drug:

protozoal infections: extraintestinal amebiasis, including amoebic liver abscess, intestinal amoebiasis (amoebic dysentery), trichomoniasis (including trichomonas vaginitis, trichomonas urethritis);
infections caused by Bacteroides spp. (including V. fragilis, B. distasonis, B. ovatus, AT. thetaiotaomicron, B. vulgatus): infections of bones and joints, central nervous system (CNS) infections, including meningitis, brain abscess, bacterial endocarditis, pneumonia, empyema and lung abscess, sepsis;
infections caused by species Clostridium spp ,, Peptococcus niger and Peptostreptococcus spp.: infection of the abdominal cavity (peritonitis, liver abscess), infections of the pelvic organs (endometritis, abscess of the fallopian tubes and ovaries, vaginal vaginal infection).

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

Contraindications:Hypersensitivity to metronidazole or other nitroimidazole derivatives, organic lesions of the central nervous system (including epilepsy), leukopenia (including in the anamnesis), liver failure (in the case of high doses), 1 trimester of pregnancy, the period of breastfeeding.

Carefully:

Pregnancy (II and III term) - only for vital reasons, renal and / or hepatic insufficiency, acute and chronic diseases of the central nervous system (risk of weighty neurological symptoms).

Pregnancy and lactation:

Metronidazole penetrates the placenta, so do not prescribe the drug in the first trimester of pregnancy, then should be used only if the potential benefit of using the drug for the mother exceeds the possible risk to the fetus.

Because the metronidazole penetrates into breast milk, reaching in it the concentrations close to the concentrations in the blood plasma, it is recommended to stop breastfeeding during treatment with the drug.

Dosing and Administration:

Intravenously sprayed or drip. Intravenous administration of metronidazole is indicated in severe infections, as well as in the absence of the possibility of taking the drug inside.

For adults and children over 12 years a single dose of 500 mg, the rate of intravenous continuous (jet) or dropwise administration - 5 ml per minute. The interval between administrations is 8 hours. The duration of treatment is determined by the individual. The maximum daily dose is no more than 4 g. Depending on the nature of the infection, the transition to maintenance therapy with oral forms of metronidazole is carried out according to the indications.

Children under the age of 12 years Metronidazole is administered 7.5 mg / kg body weight in 3 divided doses at a rate of 5 ml per minute.

Day of the prevention of anaerobic infection before the planned operation on the pelvic organs and urinary tract adults and children over 12 years Metronidazole is prescribed in the form of infusions in a dose of 500-1000 mg per day of operation and the next day at a dose of 1500 mg / day (500 mg every 8 hours).After 1-2 days usually go to maintenance therapy with oral forms of metronidazole.

Children under the age of 12 years it is recommended the administration of metronidazole intravenously drip on the same schedule in a single dose of 7.5 mg / kg body weight. The maximum daily dose in children under 12 years of age is 22.5 mg / kg body weight.

For patients with severe renal dysfunction (clearance of creatinine (KK) less than 30 ml / min) and / or liver The daily dose of metronidazole is 1000 mg, the frequency of administration is 2 times a day.

Metronidazole, a solution for infusions, is not recommended to be mixed with other medicinal products.

Side effects:

Violations of the blood and lymphatic system: leukopenia, agranulocytosis, neutropenia, thrombocytopenia, pancytopenia.

Immune system disorders: anaphylactic shock, angioedema.

Disorders of the psyche: psychotic disorders, including confusion, hallucinations; depression, insomnia, irritability, increased excitability.

Impaired nervous system: headache, dizziness, peripheral sensory neuropathy, seizures,reported on the development of encephalopathy and subacute cerebellar syndrome (disruption of coordination and synergy of movements, ataxia, dysarthria, gait disorders, nystagmus, tremor), which are reversible after metronidazole withdrawal, aseptic meningitis.

Disturbances on the part of the organ of sight: transient visual impairment, such as diplopia, myopia, vagueness of contours of subjects, reduced visual acuity, violation of color perception; Neuropathy / optic neuritis.

Disorders from the gastrointestinal tract: epigastric pain, nausea, vomiting, diarrhea, constipation, intestinal colic, decreased appetite, anorexia, taste disorder, metallic taste in the mouth, dryness of the oral mucosa, glossitis, stomatitis, pancreatitis (reversible cases), discoloration of the tongue / "lined tongue" (because of the proliferation of microflora).

Disturbances from the liver and bile ducts: increased activity of "hepatic" enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), development of cholestatic or mixed hepatitis and hepatocellular liver damage, sometimes accompanied by jaundice; in patients,treated with metronidazole in combination with other antibacterial agents, there were cases of liver failure that required liver transplantation.

Disturbances from the skin and subcutaneous tissues: rash, itching, urticaria, skin hyperemia, pustular skin rash, erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Disturbances from musculoskeletal and connective tissue: arthralgia, myalgia.

Disorders from the kidneys and urinary tract: staining urine in a brownish-reddish color, due to the presence in the urine of a water-soluble metronidazole metabolite, dysuria, cystitis, polyuria, urinary incontinence, candidiasis.

General disorders and disorders at the site of administration: nasal congestion, fever, weakness, thrombophlebitis (pain, hyperemia or swelling at the injection site), ototoxicity, pustular rash, gynecomastia.

Laboratory and instrumental data: flattening of the T wave on the electrocardiogram (ECG).

Overdose:

Symptoms: nausea, vomiting, dizziness, in more severe cases - ataxia, paresthesia and seizures.

Treatment: symptomatic and supportive therapy. There is no specific antidote.

Interaction:

Warfarin and other indirect anticoagulants. Metronidazole increases the effect of indirect anticoagulants, which leads to an increase in the time of prothrombin formation.

Disulfiram (Esperal). Simultaneous application can lead to the development of various neurological symptoms, so one should not prescribe metronidazole patients who took disulfiram in the last two weeks. Similarly, disulfram causes intolerance to ethanol.

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. Simultaneous administration of drugs stimulating enzymes of microsomal oxidation in the liver (phenobarbital, phenytoin), can accelerate the elimination of metronidazole, as a result of which its concentration in the plasma decreases.

Lithium. In patients who receive long-term treatment with lithium preparations in high doses, with the use of metronidazole, an increase in the concentration of lithium in the blood plasma and the development of symptoms of intoxication are possible.

The antimicrobial effect of metronidazole is enhanced in combination with sulfonamides and antibiotics.

With the combined administration of metronidazole and cyclosporine there may be an increase in concentration cyclosporine in the blood plasma.

Metronidazole reduces clearance fluorouracil, which can cause an increase in the toxicity of the latter.

With simultaneous application metronidazole can increase plasma concentrations busulfan.

It is not recommended to combine with nondepolarizing muscle relaxants (vecuronium bromide).

Special instructions:

With caution appoint for diseases of the kidneys, liver.

During the treatment period, ethanol intake is contraindicated (development of disulfiram-like reactions is possible: abdominal pain of spastic nature, nausea, vomiting, headache, sudden rush of blood to the face).

Long-term use of the drug is desirable to be carried out under the control of peripheral blood.

With leukopenia, the possibility of continuing treatment depends on the risk of developing an infectious process.

The appearance of ataxia, dizziness and any other deterioration in the neurological status of patients requires discontinuation of treatment.

Can immobilize treponema and lead to Nelson's false positive test.

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

During the treatment period, care must be taken when driving vehicles and engaging in potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for infusion, 5 mg / ml.

Packaging:

For 100 ml of the drug in a bottle of low-density polyethylene, closed with a lid of polypropylene.

Each vial, provided with a self-adhesive label, is placed in a bag of polypropylene BOPP film together with instructions for use in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003314

Date of registration:17.11.2015 / 14.07.2016

Expiration Date:17.11.2020

The owner of the registration certificate:Akulayf Helskea Pvt. Ltd.Akulayf Helskea Pvt. Ltd. India

Manufacturer: & nbsp

Aculife Healthcare Pvt Ltd. India

Representation: & nbspCompany AlkemiCompany Alkemi

Information update date: & nbsp09.09.2016

Illustrated instructions

Instructions

Nirmet (Nirmet)