Tseftriakson

General characteristics. Structure:

Active ingredient: 0,5 g or 1 g of a tseftriakson (in the form of sodium salt).

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the III generation of a broad spectrum of activity for parenteral administration.

Bactericidal activity is caused by suppression of synthesis of a cell wall of bacteria. It is steady in the relation β-лактамаз, the gram-positive and gram-negative microorganisms produced by the majority.

It is active concerning gram-positive aerobic microorganisms - Staphylococcus aureus (including producing a penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. the viridans groups), gram-negative aerobic microorganisms - Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Borrelia burgdorferi, Acinetobacter calcoaceticus, Haemophilus Streptococcus pneumoniae, Streptococcus pyogenes, Viridans group Streptococci), gram-negative aerobic microorganisms - Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Borrelia burgdorferi, Acinetobacter calcoaceticus, Haemophilus influenzae (including ampicillin - the resistant and producing beta lactamazu strains), Haemophilus parainfluenzae, Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis (including the strains producing beta lactamazu), Morganella morganii, Neisseria meningitidis, Neisseria gonorrhoeae (including penitsillinazoobrazuyushchy strains), Proteus mirabilis, Proteus vulgaris, Serratia marcescens, many strains of Pseudomonas aeruginosa, anaerobic microorganisms - Bacteroides fragilis, Clostridium spp. (majority of strains of Clostridium difficile of a rezistentna), Peptostreptococcus spp., Peptococcus spp.

Has activity of in vitro concerning the majority of strains of the following microorganisms, however, safety and efficiency of a tseftriakson at treatment of the diseases caused by these microorganisms clinically are not established: aerobic gram-negative microorganisms - Citrobacter diversus, Citrobacter freundii, Providencia spp. (including Providencia rettgeri), Salmonella spp. (including Salmonella typhi), Shigella spp., aerobic gram-positive microorganisms - Streptococcus agalactiae, anaerobic microorganisms - Prevotella (Bacteroides) bivius, Porphyromonas (Bacteroides) melaninogenicus.

Are steady against drug Methicillinum - resistant strains of Staphylococcus spp., many strains of streptococci of group D and strains of Enterococcus spp. (Enterococcus faecalis), Clostridium difficile, many strains of Bacteroides spp. (the producing lactamelements).

Metitsillinoustoychivye staphylococcus also Enterococcus faecalis are steady against cephalosporins, including against a tseftriakson, and enterococci, including, are also steady against a tseftriakson.

Pharmacokinetics. Absorption. After intramuscular introduction цефтриаксон it is quickly and completely soaked up in a system blood stream. Well gets into fabrics and fluid mediums of an organism: airways, bones, joints, urinary path, skin, hypodermic cellulose and abdominal organs. At an inflammation of meningeal covers well gets into cerebrospinal fluid. Bioavailability of a tseftriakson at intramuscular introduction makes 100%.

Distribution. At intramuscular introduction of a tseftriakson in a dose of 0,5 g and 1,0 g of Cmax in a blood plasma makes 38 mkg/ml and 76 mkg/ml respectively, at intravenous administration in a dose of 0,5 g, 1,0 g and 2,0 g - 82 mkg/ml, 151 mkg/ml and 257 mkg/ml respectively. At adults in 2-24 h after administration of drug in a dose of 50 mg/kg concentration in cerebrospinal fluid many times over surpasses the minimum overwhelming concentration for the most widespread causative agents of meningitis.

The equilibrium state is established within 4 days of administration of drug.

Reversible linkng with proteins of plasma (albumine) makes 83-95%.

The volume of distribution (Vd) makes 5,78-13,5 l (0,12-0,14 l/kg), children have 0,3 l/kg.

Gets through a placental barrier in small amounts.

Removal. The elimination half-life makes 6-9 h that allows to use drug of 1 times/days.

Plasma clearance - 0,58-1,45 l/h, renal clearance - 0,32-0,73 l/h.

It is removed in not changed type of 33-67% by kidneys; 40-50% - are excreted with bile in intestines where it biotransformirutsya in an inactive metabolite. About 50% are removed during 48 h.

Pharmacokinetics in special clinical cases. At newborn children kidneys excrete about 70% of drug.

At newborns and at elderly people (75 years are aged more senior), and also at patients with renal failures and a liver the elimination half-life considerably increases.

At the patients who are on a hemodialysis at CC (clearance of creatinine) of 0 - 5 ml/min., the elimination half-life makes 14,7 h; at KK of 5-15 ml/min. - 15,7 h; at KK of 16-30 ml/min. - 11,4 h; at KK of 31-60 ml/min. - 12,4 h.

At children with meningitis the elimination half-life after intravenous administration in a dose of 50-75 mg/kg makes 4,3-4,6 h.

Tseftriakson is not brought at a hemodialysis.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to a tseftriakson: infections of abdominal organs, including peritonitis, inflammatory gastrointestinal diseases, biliary tract (including a cholangitis, an empyema of a gall bladder), infections of upper and lower parts of respiratory tracts and ENT organs (including acute and chronic bronchitis, pneumonia, abscess of lungs, a pleura empyema), an epiglottiditis, infections of bones and joints, skin and soft tissues, infections of urinogenital system (including, a pyelitis, acute and chronic pyelonephritis, cystitis, prostatitis, an epididymite), contaminated wounds and burns, infections of maxillofacial area, uncomplicated gonorrhea, including, the caused microorganisms allocating a penicillinase, sepsis and a bacterial septicaemia, bacterial meningitis and an endocarditis, a venereal ulcer and syphilis, Lyme's disease (tick-borne borreliosis), a typhoid, salmonellosis and a salmonellonositelstvo, infections at patients with the weakened immunity, prevention and treatment of postoperative infectious complications.

Route of administration and doses:

The drug is administered intramusculary or intravenously (struyno or kapelno). To adults and children 12 years are aged more senior appoint 1-2 g of 1 times a day. Maximum daily dose no more than 4,0 g.

The newborn aged up to 14 days appoint 20-50 mg/kg/days. Maximum daily dose of 50 mg/kg.

To babies and children of younger age (from 15 days to 12 years) appoint 20-80 mg/kg/body weight of 1 times a day. To children with body weight> 50 kg appoint the doses intended for adults.

Doses of 50 mg/kg and more for should be entered into introductions kapelno within not less than 30 min. Patients of senile age should enter the usual doses intended for adults without amendments on age.

Course duration usually makes 4-14 days; at the complicated infections more long introduction can be required. Administration of drug should be continued within 2-3 days after disappearance of symptoms and symptoms of an infection.

At bacterial meningitis at babies and children of younger age the dose makes 100 mg/kg of 1 times/days. The maximum daily dose - 4,0 g.

Duration of therapy depends on a type of the activator and can make of 4 days at the meningitis caused by Neisseria meningitidis up to 10-14 days at the meningitis caused by sensitive strains of Enterobacteriaceae.

At Lyme's disease: to adults and children 12 years are more senior appoint 50 mg/kg of 1 times/days, the maximum daily dose - 2,0 g. Treatment duration - 14 days.

At acute uncomplicated gonorrhea the drug is administered in oil once in a dose of 250 mg.

For the purpose of prevention of postoperative complications - once 1,0 g in 30 - 60 min. prior to operation.

At operations on thick and a rectum - effectively simultaneous (but separate) Tseftriakson's introduction and one of drug of group 5 of nitroimidazoles.

Patients with renal failures have no need of dose adjustment if function of a liver remains normal. In cases of a preterminal renal failure of heavy degree with KK less than 10 ml/min. the daily dose of drug should not exceed 2,0 g.

Patients with abnormal liver functions have no need of dose adjustment if function of kidneys remains normal.

At a combination of a heavy renal and liver failure it is regularly necessary to control concentration of a tseftriakson in plasma and if necessary to adjust its dose.

To the patients who are on a hemodialysis, additional administration of drug after carrying out dialysis is not required. Speed of removal of a tseftriakson at such patients can decrease therefore it is necessary to control concentration of drug in a blood plasma for the purpose of timely dose adjustment.

Rules of preparation and administration of solutions. It is necessary to use only freshly cooked solutions. For intramuscular introduction of 0,25 g or 0,5 g of drug dissolve in 2 ml, and 1,0 g - in 3,5 ml of water for injections. For reduction of pain at injections in oil the drug should be administered with 1% lidocaine solution. Enter deeply into a gluteus or into a hip muscle. It is not necessary to enter more than 1,0 g into one muscle. It is impossible to enter solution of lidocaine of chloride in / century.

For intravenous administration of 0,25 g or 0,5 g dissolve in 5 ml, and 1,0 g of drug in 10 ml of water for injections. Solution is entered within 2-4 min.

For intravenous infusions of 2,0 g of drug dissolve in 40 ml of water for injections or one of the solutions which are not containing in the composition of calcium (0,9% chloride sodium solution; 0,45% chloride sodium solution + 2,5% dextrose solution; 5% dextrose solution; 10% dextrose solution; 6% dextran solution in 5% dextrose solution; 6-10% solution of hydroxyethylated starch). Solution is entered within 30 min.

Features of use:

Pregnancy and lactation. Use of drug at pregnancy is possible only when the estimated advantage for mother exceeds potential risk for a fruit (цефтриаксон gets through a placental barrier). In need of use of drug in the period of a lactation it is necessary to stop breastfeeding (it is allocated with breast milk).

At prolonged treatment it is regularly necessary to control a pattern of peripheral blood, indicators of a functional condition of a liver and kidneys.

In rare instances at ultrasonography of a gall bladder blackouts (precipitated calcium superphosphates of calcic salt of a tseftriakson) which disappear after drug withdrawal are noted.

At development of the symptoms or signs indicating a possible disease of a gall bladder or in the presence of an ultrasonography signs of "sladzh-phenomenon" it is recommended to stop administration of drug.

At use of drug exceptional cases of the pancreatitis which developed perhaps, owing to obstruction of bilious ways are described. Most of patients had risk factors of stagnation of bilious ways (the previous therapy by drug, serious associated diseases, completely parenteral food); at the same time it is impossible to exclude a starting role of formation of precipitated calcium superphosphates in bilious ways under the influence of a tseftriakson.

Tseftriakson does not support N-methylthiotetracindery group which causes disulfiramopodobny effects at simultaneous use of ethanol and bleeding which are inherent in some cephalosporins.

At use of drug exceptional cases of change of a prothrombin time are described. Control of a prothrombin time and purpose of vitamin K (10 mg/week) at increase in a prothrombin time prior to the beginning of can be required by patients with deficit of vitamin K (synthesis disturbance, disturbance of food) or during therapy.

Cases of fatal reactions as a result of adjournment tseftriakson-Sa2 + precipitated calcium superphosphates in lungs and kidneys of newborns are described. Theoretically there is a probability of interaction of a tseftriakson with Sa2+-soderzhashchimi solutions for intravenous administration and at other age groups of patients therefore цефтриаксон should not mix up with Sa2+-soderzhashchimi solutions (including for parenteral food), and also is entered at the same time, including through separate accesses for infusions on various sites.

Data on possible interaction of a tseftriakson with peroral calcium - the containing drugs, and also a tseftriaksona for introduction in oil about calcium - the containing drugs (in/in and peroral) are absent.

At treatment tseftriaksony false positive results of test of Koombs, test on a galactosemia can be noted, when determining glucose in urine (the glucosuria is recommended to be determined only by a fermental method).

Despite detailed collecting the anamnesis it is impossible to exclude a possibility of development of anafilatichesky shock that demands immediate therapy: at first enter intravenously Epinephrinum, then - glucocorticosteroids.

The researches in vitro showed that it is similar to other cephalosporins, цефтриаксон is capable to force out the bilirubin connected with blood serum albumine. Therefore at newborns with a hyperbilirubinemia and, especially at premature newborns, use of a tseftriakson demands big care.

Side effects:

Allergic reactions: rash, itch, fever, fever.

From a nervous system: headache, dizziness.

From bodies of a GIT: diarrhea, nausea, vomiting, taste disturbance, meteorism, pseudomembranous colitis.

From system of a hemopoiesis: at prolonged use in high doses changes of a picture of peripheral blood are possible (anemia, including hemolitic), an eosinophilia, a thrombocytosis, a leukopenia, a neutropenia, a lymphopenia, thrombocytopenia).

From urinogenital system: vagina candidiasis, vaginitis.

Local reactions: at in introduction - phlebitis, morbidity, consolidation on the vein course; introduction in oil - morbidity, a caumesthesia, tightness or consolidation in an injection site.

Laboratory indicators: increase (reduction) in a prothrombin time, increase in activity of "hepatic" transaminases and ShchF, hyperbilirubinemia, giperkreatininemiya, increase in concentration of urea, existence of a deposit in urine.

Others: the increased sweating, rushes of blood to the person.

Undesirable reactions with a frequency less than 0,1%: abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, cholelithiasis, bronchospasm, colitis, dyspepsia, nasal bleeding, abdominal distention, stagnation of bile (sladzh-syndrome), glucosuria, hamaturia, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, heartbeat, spasms, serum disease.

Others: stomatitis, glossitis, oliguria, rash, allergic dermatitis, small tortoiseshell, hypostasis, multiformny erythema, Stephens-Johnson's syndrome, Lyell's disease.

Interaction with other medicines:

Bacteriostatic antibiotics reduce bactericidal effect of a tseftriakson. Tseftriakson and aminoglycosides possess a synergism concerning many gram-negative bacteria (including Pseudomonas aeruginosa), the drugs should be administered separately in the recommended doses.

Tseftriakson, suppressing an indestinal flora, interferes with vitamin K synthesis. At co-administration with the drugs reducing aggregation of thrombocytes (NPVS, salicylates, Sulfinpyrazonum) the risk of development of bleedings increases.

At co-administration with anticoagulants strengthening of anticoagulating action is noted.

At co-administration with "loopback" diuretics and other nefrotoksichny drugs the risk of development of nephrotoxic action increases. Does not interact with probenetsidy.

Pharmaceutical interaction. Tseftriakson it is impossible to mix with solutions, calciferous (including Hartman and Ringer's solution).

Pharmaceutical it is not compatible to the solutions containing other antibiotics including with amsakriny, Vancomycinum, flukonazoly and aminoglycosides.

Contraindications:

Hypersensitivity to a tseftriakson and other cephalosporins, penicillin, karbapenema; first trimester of pregnancy, lactation period.

With care: premature children, a renal and/or liver failure, the nonspecific ulcer colitis, enteritis or colitis connected using antibacterial drugs, the second and third trimester of pregnancy.

Overdose:

Now about drug overdose cases Tseftriakson it was not reported. Symptoms of overdose is strengthening of side effects of drug - see above.

Treatment: symptomatic. There is no specific antidote. The hemodialysis and peritoneal dialysis are not effective.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 0,5 g or 1,0 g of a tseftriakson in a bottle from colourless glass. The bottle is hermetically corked by a sterile rubber bung and pressed out by a cap aluminum with a plastic cover. On 1 bottle together with the instruction on a medical use in a cardboard pack. Packaging for hospitals: 25 bottles on 0,5 g or 1,0 g together with instructions on a medical use in a cardboard box. Bottles separate between ranks laying from a cardboard.