Потентокс

General characteristics. Structure:

Active ingredients: 1000 tsefepima of a hydrochloride, 250 mg of amikacin of sulfate.

The antibacterial drug possessing a broad spectrum of activity, high bactericidal activity concerning the majority of causative agents of hospital infections, including resistant to many antibiotics

Pharmacological properties:

Pharmacodynamics. Tsefepima a hydrochloride - a tsefalosporinovy antibiotic of the IV generation. Suppresses synthesis of enzymes of a wall of a bacterial cell. Has a broad spectrum of activity concerning various gram-positive and gram-negative microorganisms, including strains, resistant to aminoglycosides and to tsefalosporinovy antibiotics of the third generation, such as ceftazidime. Tsefepim is steady against action of the majority beta лактамаз, has insignificant affinity to a beta laktamaz, coded by chromosomal genes, and quickly gets into gram-negative bacterial cells.

Amikacin sulfate - a semi-synthetic antibiotic from group of aminoglycosides III of generation with a wide range of bactericidal action. Actively getting through a cellular membrane of bacteria, it is irreversible communicates with 30S in subunit of bacterial ribosomes, suppresses protein synthesis of microorganisms that leads to his death. It is highly effective concerning gram-negative bacteria and some gram-positive bacteria (Staphіlococcus spp.), including steady against penicillin.

Potentoka is active against such microorganisms:

gram-positive aerobes: Staphylococcus aureus (including the strains producing beta lactamazu); Staphylococcus epіdermіdіs (including the strains producing beta lactamazu); drguy strains of stafilokokk, including S. saprophytіcus; Streptococcus pyogenes (group A streptococci); Streptococcus agalactіae (group B streptococci); Streptococcus pneumonіae (including strains of average resistance to penicillin - MPK від 0,12 to 1 mkg/ml); other beta and hemolitic streptococci (C, G groups, F), S. bovіs (group D), streptococci of group ("vіrіdans").

Gram-negative aerobes: Acіnetobacter lwoffіi, Acіnetobacter baumann іі; Aeromonas hydrophіla; Capnocytophaga spp.; Cіtrobacter spp., including C. dіversus, C. freund іі; Campylobacter jejun і; Cardnerella vagіnalіs; Enterobacter spp., including E. cloacae, E. aerogenes, E. agglomerans, E. sakazak іі; Escherіchіa col і; Haemophіlus ducrey і; Haemophіlus іnfluenzae (including the strains producing beta lactamazu); Haemophіlus paraіnfluenzae; Hafnіa alve і; Klebsіella spp., including K. pneumonіae, K. oxytoca, K. ozaenae; Legіonella spp.; Morganella morgan іі; Moraxella catarrhalіs (including the strains producing beta lactamazu); Neіsserіa gonorrhoeae (including the strains producing beta lactamazu); Neіsserіa menіngіtіdіs; Proteus spp., including P. mіrabіlіs, P. vulgarіs; Provіdencіa spp. (including P. rettger і, P. stuart іі); Pseudomonas spp., including P. aerugіnosa, P. putіda, P. stutzer і; Salmonella spp.; Serratіa spp. (including S. marcescens, S. lіquefacіens); Shіgella spp.; Yersіnіa enterocolіtіca.

Separate strains of Stenotrophomonas maltophіlіa can be steady.

Anaerobe bacterias: Bacteroіdes spp., including B. melanіnogenіcus and other microorganisms of an oral cavity relating to bacteroids, Clostrіdіum perfringens, Fusobacterіum spp., Mobіluncus spp., Peptostreptococcus spp., Veіllonella spp.

Потентокс it is inactive concerning Bacteroіdes fragіlіs and Clostrіdіum dіffіcіle.

Pharmacokinetics. Both antibiotics are well absorbed at intramuscular introduction. The peak of concentration in a blood plasma at healthy volunteers is defined in 1 hour after intramuscular introduction of 1,25 g of drug and makes 65 mg/ml for a tsefepim and 23 mg/ml for amikacin. In 12 hours the level of a tsefepim decreases in a blood plasma to 1 mg/ml, and amikacin - to 2 mg/ml. Tsefepim and amikacin act synergy, thanks to it have the broad range of action in a human body, extends to gram-positive and gram-negative bacteria. Removal of means is carried out generally through kidneys, an average elimination half-life - 2 hours (± 0,3) and the general clearance – 94-120 (± 10) by ml/min. at healthy patients.

Use of mix of a tsefepim and amikacin is not followed by either chemical, nor physical and chemical incompatibility.

Potentoks's pharmacokinetics at introduction of 650 mg – 1,5 g is linear. There are no confirmations concerning accumulation in an organism of the healthy person which entered clinically significant doses within 5 days.

Tsefepim. At intramuscular introduction it is quickly and completely acquired. In urine, bile, peritoneal liquid, a secret of bronchial tubes, a phlegm, a prostate, an appendix and a gall bladder therapeutic concentration to a tsefep_m are reached. The elimination half-life of a tsefepim from an organism averages about 2 hours. At the healthy people receiving doses to 2 g intravenously with an interval of 8 hours within 9 days cumulation of drug in an organism was not observed. The average general clearance makes 120 ml/min. Tsefepim is allocated almost only for the account of renal mechanisms, mainly by glomerular filtering (the average renal clearance makes 110 ml/min.). In urine about 85% of a dose in the form of not changed tsefepim are found. Zvyazyvaniye of a tsefepim with proteins of plasma less than 19% also does not depend on concentration of drug in blood serum.

Amikacin sulfate. At intramuscular introduction it is quickly and completely soaked up. Liquid, liquid of abscesses is distributed in extracellular liquid, including blood serum, a lymph, pericardiac, synovial, peritoneal liquids, a pleural exudate, an astsitichna. High concentration are found in urine. Low concentration - in bile, breast milk, a bronchial secret, a phlegm and liquor. At an inflammation of a meninx penetration into liquor increases. Gets into all body tissues where collects in a cell. High concentration are noted in a liver, lungs, kidneys (in a kidney amikacin collects in cortical substance). An elimination half-life adults - 2-4 hours, at newborns have 5-8 hours, children of advanced age have 2,5-4 hours. About 75-95% are removed by kidneys in not changed look by glomerular filtering.

Children. Drug pharmacokinetics assessment потентокс was carried out at children aged from 2 months up to 11 years after introduction of one or several doses of drug. Absolute bioavailability of a tsefepim at intramuscular injections in a dose of 50 mg/kg makes 82,3 (± 15) %. The elimination half-life is inversely proportional post-natal age and renal clearance of both antibiotics. Gender and age of patients have no significant effect on the general clearance from an organism and distribution volume taking into account the amendment on body weight. Exposure of a tsefepim at children after intravenous administration in a dose of 50 mg/kg is comparable with exposure of an intravenous dose of 2 g at adults. The volume of distribution of drug is defined by amikacin.

Patients of advanced age. The drug dosage for patients of advanced age demands correction depending on clearance of creatinine.

Potentoks's pharmacokinetics was investigated with participation of patients of advanced age with average clearance of creatinine 64 (± 15) ml/min. Increase in an elimination half-life of Potentoks from an organism depending on values of clearance of creatinine was observed. It is desirable to calculate the greatest and smallest concentration in serum right after carrying out a course of treatment. The highest concentration in a blood plasma is observed in 30-90 minutes after an injection.

The researches conducted at patients with various degree of a renal failure showed increase in an elimination half-life of means from an organism. At patients with reduced function of kidneys (the clearance of creatinine is less or it is equal to 60 ml/min.) the dose should be selected individually. On average the elimination half-life at the patients with heavy renal failures who are on dialysis makes 13 hours for a hemodialysis and 19 hours for peritoneal dialysis. The drug pharmacokinetics at patients with the broken function of a liver is not changed. Dose adjustments such patients do not need.

Indications to use:

• Bacterial septicaemia,
• respiratory infections (not hospital and nozokomialny pneumonia, including with complications),
• infections of skin and its appendages,
• infections of an urinary system and the complicated infections of an urinary system (acute and chronic pyelonephritis) except initial treatment of the first episode of infections of an urinary system as the potential advantage is limited to nephrotoxic effect of amikacin of sulfate,
• infections of bones and joints (osteomyelitis, arthritis),
• infections of abdominal organs (peritonitis, cholecystitis),
• meningitis,
• burns.

For identification of a microorganism activator (activators) and definition of sensitivity to Potentoks it is necessary to carry out the corresponding tests. After obtaining results of treatment using antibiotics it is necessary to correct as appropriate. However Potentoks can be applied in the form of monotherapy even before identification of a microorganism activator because has a wide range of antibacterial action of rather gram-positive and gram-negative microorganisms.

Route of administration and doses:

Before introduction it is necessary to carry out skin tests on individual sensitivity to drug on condition of lack of contraindications for their carrying out.

The daily dose for adults makes 1,25-2,5 g which is appointed once or twice a day equal doses depending on type and the course of a disease.

Calculation of the corresponding dose is defined by body weight. Потентокс it is possible to enter intravenously and intramusculary.

Before treatment it is necessary to determine creatinine level in blood serum and to calculate clearance of endogenous creatinine. Definition of an urea nitrogen of blood is not a reliable indicator of function of kidneys. During prolonged treatment periodically it is necessary to carry out repeated assessment of function of kidneys.

It is desirable to calculate the greatest and smallest value of concentration of Potentoksu in blood serum during performing treatment. Concentration in blood serum should not exceed 35 mkg/ml (counting on Amikacin sulfate) in 30-90 minutes after an injection. The following injection it is possible to carry out at Potentoksu's concentration 10 mkg/ml (counting on Amikacin sulfate).

Intramuscular introduction to patients with normal function of kidneys: the recommended dose for adults and children is more senior than 12 years makes 15 mkg/kg/days (counting on Amikacin sulfate), divided into 2 equal doses entered through identical spans. Doses which are appointed for treatment of patients with excess body weight should not exceed 1,5 g/days.

To the full-term newborns and children aged from 2 months and up to 12 years, it is recommended, at first 10 mg/kg (counting on Amikacin sulfate), then to 7,5 mg/kg there are each 12 hours.

Treatment duration – 7-10 days.

The recommended doses for adults and ways of introduction are presented in table 1.

Place and type of an infection	Dose	Interval, hours	Duration of treatment (days)
Pneumonia and other heavy infections	2,5 g in/in or in oil	12	10
Other moderately severe infections	1,25 g in/in or in oil	12	7-10
Moderately severe and heavy uncomplicated infections of skin and skin appendages.	2,5 g in/in or in oil	12	10
Empirical treatment of patients with a febrile neutropenia.	2,5 g in/in	8	7 **
Easy and the moderately severe uncomplicated or complicated infections of urinogenital system.	0,625-1,25 g in/in or in oil ***	12	7-10
The heavy uncomplicated or complicated infections of urinogenital system.	2,5 g in/in or in oil	12	10
Complicated intraperitoneal an infektsiiya.	2,5 g in/in	12	7-10

** At patients whose body temperature decreased to norm, but the neutropenia continues to be defined more than 7 days, it is necessary to resolve an issue of continuation of treatment using germicides.

*** Intramuscular introduction is appointed only for treatment of the infections of an uric path caused by E. coli if such method of introduction is considered more suitable.

Intravenous administration to patients with normal function of kidneys: Потентокс enter intravenously within 30-60 minutes.

At a renal failure the first single dose (counting on amikacin sulfate) - 7,5 mg/kg. The subsequent doses are determined by a formula:

(1 dose (mg) × KK)/100, where KK - clearance to a kreat_n_n in ml/min. / 1,73 sq.m.

At intramuscular introduction solution is entered deeply into an upper outside quadrant of a buttock.

Color of powder of Potentoksu, and also solution, darkens depending on storage conditions. At storage in the recommended conditions activity of drug does not change.

Features of use:

It is contraindicated during pregnancy or feeding by a breast. In need of drug use feeding by a breast should be stopped.

Children. It is recommended to apply to children aged from 2 months. Safety of treatment at children is younger than 2 months is not proved. The sufficient clinical data confirming expediency of use of Potentoksu at treatment of children aged up to 2 months or children with the heavy infections caused by Haemophіlus influenzae type b no.

Before treating using Potentoksu for injections, it is necessary to define whether were at the patient of reaction of hypersensitivity to a tsefepim, to cephalosporins, penicillin and amikacin or another beta лактамным or aminoglikozidny antibiotics. It is necessary to appoint antibiotics with care all patient with any forms of an allergy, especially to medicines. In case of allergic reaction to drug it is necessary to stop its use. Heavy acute reactions of hypersensitivity demand performing urgent treatment using Adrenalinum hydrochloricum, corticosteroids, antihistaminic, angiotonic amines and the use of other actions, including ensuring passability of respiratory tracts and oxygen therapy.

When using practically of all antibiotics of a broad spectrum of activity it was reported about cases of pseudomembranous colitis. Therefore in case of developing of diarrhea during treatment by Potentoks it is necessary to stop administration of drug, hard cases demand special treatment. Easy forms of colitis can pass after administration of drug, moderate or serious conditions can demand special treatment.

As well as in a case with other antibiotics, use of drug can lead to colonization by insensitive microflora. At development of superinfections during treatment it is necessary to take the appropriate measures.

For prevention of complications and reduction of frequency of their development drug is recommended to be used under control of function of kidneys, hearing and a vestibular mechanism (at least once a week) and concentration of drug in blood serum.

As drug is removed with urine, prior to treatment it is necessary to carry out correction of water and electrolytic balance at the patient. During treatment by drug it is necessary to use enough liquid, to often define concentration of creatinine in a blood plasma and in case of need to adjust the scheme of dosing.

Correction of the mode of dosing depending on clearance of creatinine is necessary for patients with disturbances of secretory function of kidneys. The main toxic effect of drug at parenteral administration is its action on the VIII couple of cranial nerves. Usually at first dullness in the range of sounds of high frequency is defined that can be revealed at an audiometric research. At patients with a renal failure the risk of development of ototoksichesky complications is considerably increased. If during treatment progressing of a renal failure is observed, it is recommended to conduct audiometric researches and in case of need to stop drug use.

Patients with a renal failure have to have a reduced daily dose and/or an interval between doses also minimizing of risk of ototoxicity is increased respectively to concentration of creatinine in blood serum for prevention of accumulation of drug in blood. If there are ototoxicity signs (for example, dizziness, a ring, a sonitus or decrease in hearing) or nephrotoxicity (frequent desires to an urination, identification of leukocytes, erythrocytes and albumine in urine, decrease in clearance of creatinine, an oliguria), it is necessary to increase liquid reception, use of drug has to be stopped or it is necessary to reduce a dose. The specified symptoms usually disappear by the end of a course of treatment. However, if there are manifestations of an azotemia or the oliguria accrues, treatment has to be stopped. The ototoxicity caused by aminoglikozidny antibiotics can develop also after the end of use of drug and usually has irreversible character. The risk of development of ototoxicity is increased at patients with an impaired renal function, and also at use of high doses or at prolonged treatment by drug.

With care it is necessary to use drug sick parkinsonism, to patients who have disturbances of nervnomyshechny conductivity in connection with possibility of kurarepodobny effect, and also to elderly people.

Patients of advanced age should reduce a drug dose in connection with decrease in functional activity of kidneys and possible decrease in body weight. It is necessary to estimate functional activity of kidneys regularly. The analysis of urine to is necessary or during treatment.

At patients with organism dehydration the possibility of risk of toxicity increases because of increase in concentration of drug in blood serum.

In case of lack of the expected clinical answer in 3-5 days treatment should be stopped and carried out definition of sensitivity of the activator to antibiotics.

It is necessary to take with caution drug to patients whose activity demands speed of psychomotor reactions (management of transport, work with potentially dangerous mechanisms), considering risk of emergence of possible undesirable reactions from a nervous system.

Side effects:

Symptoms from a digestive tract and reaction of hypersensitivity were the most frequent side effects.

Gastrointestinal frustration: nausea, vomiting, diarrhea, abdominal pain, lock, oral cavity candidiasis, colitis (including pseudomembranous).

Gepatobiliarny frustration: increase in activity of ASAT and ALAT, increase in an alkaline phosphatase and bilirubin, abnormal liver function, including cholestasia.

Disturbances from immune system: hyperthermia, fever, Quincke's edema, anaphylaxis, including acute anaphylaxis.

Disturbances from kidneys and an urinary system: nephrotoxicity – a renal failure (an oliguria, an albuminuria, a cylindruria, a leukocyturia, a hyperazotemia, a proteinuria, a microhematuria, a hamaturia, increase in level of creatinine and urea), an acute necrosis, intersticial nephrite, an acute renal failure.

Disturbances from a vestibular mechanism and acoustic organs: toxic influence on the eighth cranial nerve can cause relative deafness, balance loss, vestibular frustration, dizziness, a sonitus. Amikacin generally influences acoustical function. Cochlear damages provides high-frequency irreversible deafness and it is often observed before becomes possible clinically to define a hearing disorder.

Neurologic frustration: encephalopathy (a loss of consciousness, hallucinations, a stupor, a coma), a headache and dizziness, drowsiness, paresthesias, a tremor, paresis of muscles, a myoclonus, disturbances of neuromuscular conductivity, emergence of nervnomyshechny blockade (muscular paralysis, respiratory depression) is possible. Spasms, an apnoea can be observed at patients with a renal failure if Potentoksu's dose for them was not listed in connection with creatinine level. At the spasms caused by Potentoksu's use, use of drug should be stopped.

Cardial frustration: vasculitis, arterial hypotension, vazodilatation.

Gastrointestinal frustration: nausea, vomiting, diarrhea, abdominal pain, lock, oral cavity candidiasis, colitis (including pseudomembranous).

Gepatobiliarny frustration: increase in activity of ASAT and ALAT, increase in an alkaline phosphatase and bilirubin, abnormal liver function, including cholestasia.

Metabolic frustration: hypomagnesiemia.

Disturbances from system of blood and lymphatic system: anemia, hypoplastic anemia, hemolitic anemia, leukopenia, neutropenia, agranulocytosis, granulocytopenia, thrombocytopenia, pancytopenia, eosinophilia, prothrombinopenia, increase in a prothrombin time or partial trombolastinovy time (PTT).

Disturbances from connecting fabric and a musculoskeletal system: arthralgia.

Disturbances from immune system: hyperthermia, fever, Quincke's edema, anaphylaxis, including acute anaphylaxis.

Changes from skin and hypodermic cellulose: skin rashes, urticaria, erythema, itch, Stephens-Johnson's syndrome, polymorphic erythema, toxic epidermal necrolysis.

Respiratory frustration: disorders of breath.

Frustration of reproductive system and mammary glands: vaginitis, genital itch, candidiasis.

Local reactions: a hyperemia, hypostasis, post-injection lipodystrophies in an injection site of injections, pain, consolidation in an injection site, phlebitis.

Laboratory indicators: a positive take of the test of Koombs without hemolysis.

Interaction with other medicines:

Drug is not recommended to be mixed with ampicillin solutions at concentration more than 40 mg/ml, also with metronidazole, Vancomycinum, gentamycin, Tobramycinum, нетилмицин sulfate or Aminophyllinum in connection with possible interaction. However, if parallel treatment using Potentoksu and the above-stated medicines is appointed, each of these antibiotics can be applied separately, without mixing.

It is necessary to control attentively function of kidneys and hearing at Potentoksu's use. It is not necessary to apply in parallel Potentoks with diuretic drugs (Acidum etacrynicum or furosemide) as they can increase ototoxicity and nephrotoxicity. Besides, at intravenous administration diuretic drugs can increase Potentoksu's toxicity by change of concentration of antibiotics in blood serum and fabrics.

Simultaneous use of Potentoks with anticoagulants, heparin or trombolitikam can increase risk of bleeding.

Потентокс, suppressing an indestinal flora, interferes with vitamin K synthesis. Therefore at simultaneous use with the drugs reducing aggregation of thrombocytes (nonspecific anti-inflammatory drugs, salicylates) the risk of development of bleedings increases. Use of drug together with anesthetics and muscle relaxants leads to blockade of neuromuscular transfer and paralysis of respiratory muscles.

At simultaneous use of drug with Amphotericinum In, Vancomycinum, metoksiflurany, enflurany, indometacin, fen_lbutazy and other NPVS, X-ray contrast means, cefalotin, cyclosporine, Cisplatinum, polymyxins the risk of development of nephrotoxic action increases. At use of drug along with intravenous administration of indometacin to premature babies, increase in concentration of drug in a blood plasma and emergence of risk of development of toxicity is possible.

To avoid possible medicinal interaction with other drugs, drug solutions (as well as the majority of other b-laktamnykh of antibiotics) do not enter along with solutions of metronidazole, Vancomycinum, gentamycin, Tobramycinum of sulfate and a netilmitsin of sulfate. In case of purpose of drug with the specified drugs enter each antibiotic separately.

Also strengthening of neuromuscular blocking is noted at simultaneous use with means for an inhalation anesthesia, opioid analgetics, magnesium of sulfate and at transfusion of a large amount of blood from tsitratny preservatives.

At simultaneous use of drug with other aminoglikozidny antibiotics the risk of emergence of the listed side effects increases. It is impossible to appoint at the same time two aminoglycosides or to replace one drug with another if the first aminoglycoside was applied within 7-10 days. A repeated course can be conducted not earlier than in 4-6 weeks.

At simultaneous introduction with antibiotics of penicillinic group concentration of drug in blood serum can decrease.

Contraindications:

Hypersensitivity to a tsefepim, amikacin, to antibiotics of a tsefalosporinovy class, penicillin or other b-laktamnym to antibiotics, to antibiotics of aminoglikozidny group and their derivatives. Heavy renal failures, an azotemia (level of residual nitrogen is higher than 150 mg of %). Neuritis of an acoustical nerve, dysfunction of a vestibular mechanism. Myasthenia гравис.

Overdose:

Symptoms: from - and nephrotoxic effect of drug, neuromuscular blockade, a sonitus, acoustical frustration, skin rashes, an itch, nausea, vomiting, a headache, dizziness, fever, paresthesias, depression of function of kidneys (renal failure), hallucination, consciousness disturbance, a stupor, a coma, a myoclonia, epileptoformny attacks, neuromuscular irritability, oppression or paralysis of breath, in cases of considerable exceeding of the recommended doses, especially at patients with an impaired renal function amplify manifestations of side effect.

Treatment. It is necessary to stop administration of drug, to carry out symptomatic therapy. Providing a conclusion of Potentoksu from an organism requires carrying out a hemodialysis. Heavy allergic reactions of immediate type demand use of adrenaline and other forms of an intensive care. At the first signs of blockade of nervnomyshechny conductivity it is necessary to stop administration of drug of Potentoks and to immediately enter intravenously solution of Calcii chloridum or subcutaneously solution of a prozerin and atropine. In case of need the patient is transferred to an artificial respiration.

Storage conditions:

To store at a temperature not above 25 °C in original packaging in the place, unavailable to children. Period of validity 2 years.

Issue conditions:

According to the recipe

Packaging:

On 1 bottle in a cardboard pack.