Metrid 0.5% 100 ml infusion solution (vial)

The instruction for medical use of METRID medicine the Trade name Metrid Mezhdunarodnoye the unlicensed name Metronidazole Dosage Form Solution for infusions, 0.5% 100 ml Structure of 100 ml of solution contain active agent: metronidazole of 500 mg, excipients: sodium chloride, citric acid monohydrate, dinatrium hydrophosphate anhydrous, water for injections. The description Transparent colourless or light yellow color solution Pharmacotherapeutic group Antibacterial drugs for system use. Other antibacterial drugs. Imidazole derivatives. Metronidazole the ATX J01XD01 Code the Pharmacological Pharmacokinetics Distribution Later properties of intravenous administration in a dose of 500 mg within 20 min. the maximum concentration 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, the minimum concentration at the subsequent introduction – 18 mkg/ml. At intravenous administration the maximum concentration is reached in 30-60 min., therapeutic concentration remains during 6-8 h. At normal bile production the concentration of metronidazole in bile after intravenous administration can exceed considerably concentration in plasma. Linking with proteins of plasma – 10-20%. Distribution volume 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 a blood-brain barrier, passes through a placental barrier. Metabolism Is metabolized (about 30-60%) by hydroxylation, oxidation and a glyukuronirovaniye. The main metabolite – the 2nd oxymetronidazole – has antiprotozoan and antimicrobial effect. Removal Is removed by kidneys (60-80%), 20% - in not changed look, through intestines 6-15% are removed. Elimination half-life – 8 h (6-12 h). Renal clearance – 10.2 ml/min. The pharmacokinetics in special clinical cases At alcoholic damage of a liver elimination half-life makes 18 h (10-29 h), at the newborns who were born at the 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 the cumulation of metronidazole in blood serum can be observed. Pharmacodynamics Antiprotozoan and antimicrobial drug, derivative 5 nitroimidazoles. The mechanism of action consists in biochemical restoration 5 nitrogroups intracellular transport proteins of anaerobic microorganisms and protozoa. The restored 5 nitrogroup interacts with DNA, inhibiting its synthesis that leads to death of bacteria. Drug is active concerning protozoa: Trichomonas vaginalis, Entamoeba histolytica, Gardnerella vaginalis, Giardia intestinalis, Lamblia spp., anaerobic bacteria: Bacteroides spp. (including Bacteroides fragilis, Bacteroides distasonis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Fusobacterium spp., Veillonella spp., Prevotella spp. (Prevotella bivia, Prevotella buccae, Prevotella disiens), Eubacterium spp., Clostridium spp., Peptococcus spp., Peptostreptococcus spp. The minimum overwhelming concentration for these strains makes 0.125-6.25 mkg/ml. In combination with amoxicillin shows activity concerning Helicobacter pylori (amoxicillin suppresses development of resistance to metronidazole). Aerobic microorganisms and facultative anaerobes, but in the presence of the mixed flora are resistant to drug (aerobes and anaerobe bacterias) metronidazole works synergy with the antibiotics effective against aerobes. Drug increases sensitivity of tumors to radiation, has disulfiramopodobny effect, stimulates reparative processes. Indications Treatment of the infectious and inflammatory diseases caused by activators, sensitive to drug, that number: - severe forms of a hepatic and intestinal amebiasis - infections of bones and joints, including osteomyelitis - infections of the central nervous system, including meningitis, brain abscess - a bacterial endocarditis - necrotizing pneumonia, an empyema, abscess of lungs - infections of an abdominal cavity, including 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 surgical interventions) - infections of skin and soft tissues - sepsis, gas gangrene - as the radio sensibilizing means at radiation therapy (in cases when the resistance of a tumor is caused by a hypoxia in tumor cells) - prevention and treatment of postoperative infections (especially after operations on a colon, near-rectal area, appendectomy, gynecologic interventions) the Route of administration and doses Drug is intended for intravenous infusions. To adults and children 12 years drug are more senior appoint 0.5-1 g (duration of infusion of 30-40 min.) in an initial dose. Then each 8 h on 500 mg with a speed of 5 ml/min. At good tolerance after the first 2-3 infusions pass to jet introduction. A course of treatment – 7 days. The maximum daily dose – 4 g. According to indications pass to the supporting intake in a dose 400 mg 3 times a day. To children aged up to 12 years appoint according to the same scheme in a single dose 7.5 mg/kg (1.5 ml). At it is purulent - septic diseases usually conduct 1 course of treatment. In the preventive purposes to adults and children 12 years are more senior appoint by drop infusion 0.5-1 g on the eve of operation, in day of operation and next day – 1.5 g a day (on 500 mg each 8 h). In 1-2 days pass to maintenance therapy (intake of metronidazole inside). For patients with chronic kidney disease (at KK less than 30 ml/min.) and/or with a liver failure the maximum daily dose makes 1 g (at frequency rate of introduction 2 times a day). As the radio sensibilizing means the drug is administered intravenously by drop infusion, at the rate of 160 mg/kg or 4-6 g/m2 of a body surface for 0.5-1 h prior to radiation. Apply before each session of radiation within 1-2 weeks. During the remained radiotheraphy period metronidazole is not applied. The maximum single dose – 10 g, course – 60 g. Side effects Very often (≥1/10) - a headache - nausea Often (≥1/100 to & lt, 1/10) - an abdominal pain, gripes in a stomach - diarrhea 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 - pancreatitis - darkening of urine is Very rare (& lt, 1/10000) - a neutropenia (leukopenia) - anaphylactic reactions - thrombophlebitis - 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. Contraindications - hypersensitivity to components of drug and other derivatives of a nitroimidazole - a leukopenia (including in the anamnesis) - organic lesions of the central nervous system, including epilepsy - a liver failure (at use of drug in high doses) - pregnancy (I trimester) - the lactation period - a heavy renal failure Medicinal interactions At simultaneous use of Metrid: - with indirect anticoagulants the increase in a prothrombin time is noted, - with drugs of salts of lithium the increase in concentration of lithium in blood plasma and development of symptoms of intoxication is possible, - with Prednisolonum – removal of metronidazole from an organism owing to acceleration of his metabolism in baking under the influence of Prednisolonum increases, - with Cimetidinum - the metronidazole metabolism inhibition is noted that can lead to increase in concentration of metronidazole in blood plasma and to increase in risk of development of side reactions, - with the drugs stimulating microsomal enzymes of a liver (Phenytoinum, phenobarbital) the metronidazole removal can accelerate therefore its concentration in blood plasma decreases, - with rifampicin - the clearance of metronidazole from an organism, - with Phenytoinum – perhaps small increase in concentration of Phenytoinum in blood plasma increases, the case of development of toxic action is described, - with ftoruratsily - toxic action, but not effect of a ftoruratsil amplifies, - with ethanol the development of disulfiramopodobny reactions is noted, - with Disulfiramum - can bring to development of neurologic reactions (the interval between appointment has to make not less than 2 weeks). Streptocides and antibiotics strengthen antimicrobial effect of metronidazole. It is not recommended to combine with not depolarizing muscle relaxants (for example, a vekuroniya bromide). 18 years are not recommended to use drug in a combination with amoxicillin at patients more young. Pharmaceutical interaction Metronidazole for intravenous administration is not recommended to be mixed with other medicines. Special instructions Should be considered that during use of drug the alcohol intake as development of disulfiramopodobny reaction is possible is contraindicated (a spastic abdominal pain, nausea, vomiting, a headache, sudden rush of blood to the person). At long therapy it is necessary to control a blood pattern. At a leukopenia the possibility of continuation of treatment depends on risk of development of infectious process. With care to apply in diseases of a liver and kidneys. At development of neurologic symptoms (the ataxy, dizziness and any other symptoms of deterioration in the neurologic status) should stop drug use. Drug can immobilize treponemas and lead to the false positive test of Nelson. Drug it is necessary to appoint pregnancy and the period of a lactation In II and III trimesters of pregnancy only according to vital indications, having carefully estimated the expected advantage of therapy for mother and potential risk for a fruit. Use in pediatrics is not recommended to use drug in a combination with amoxicillin at patients more young than 18 years. The feature of influence on ability to run the vehicle and potentially dangerous mechanisms needs to warn the patient that drug can reduce concentration of attention, at control of motor transport or other potentially dangerous mechanisms. Overdose Symptoms: strengthening of side effects. Treatment: carry out symptomatic treatment. Metronidazole and its main metabolites are removed at a hemodialysis (elimination half-life is reduced to 2.6 h). At peritoneal dialysis it is removed in insignificant quantities. A form of release and packing On 100 ml of drug in the polyethylene bottle disposable corked by a special cap for infusions. On a bottle paste the paper self-adhesive label. Each bottle is packed into a plastic bag. On 1 bottle together with the instruction for use in the state and Russian languages place in a cardboard box. To Store storage conditions in the place protected from light at a temperature not higher than 30 wasps. Not to freeze! To store out of children's reach! 3 years not to apply a period of storage after an expiration date! Prescription status from drugstore According to the prescription Otsuka Pharmaceutical India Private Limited Producer of Vasan – Chacharvadi, Sanand, Ahmedabad – 382,213, India the Owner of the registration certificate of Otsuka Pharmaceutical India Private Limited, India the Address of the organization accepting in the territory of the Republic of Kazakhstan claims from consumers on quality of products (goods) Almaty, Zheltoksan Ave., 115, office 370 Ph./fax: (727) 295 24 44
To develop