Tseftriakson

General characteristics. Structure:

Active ingredient: 1,0 g of a tseftriakson of sodium (in terms of active agent).

Antibiotic of a broad spectrum of activity with pronounced bactericidal action.

Pharmacological properties:

Pharmacodynamics. Tseftriakson - a tsefalosporinovy antibiotic of the III generation for parenteral use, possesses bactericidal action, synthesis of a cellular membrane oppresses, in vitro suppresses growth of the majority of gram-positive and gram-negative microorganisms. Tseftriakson is steady in the relation beta лактамазных enzymes (both a penicillinase, and a tsefalosporinaza, produced by the majority of gram-positive and gram-negative bacteria). It is effective concerning the following microorganisms.

Gram-positive Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus V (Str. agalactiae), Streptococcus viridans, Streptococcus bovis.

Note: Staphylococcus spp., steady against Methicillinum, резистентен and to cephalosporins, including to a tseftriakson. The majority of strains of enterococci (for example, Streptococcus faecalis) are also steady against a tseftriakson.

Gram-negative Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., En-terobacter spp. (some strains are steady), Eschenchia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Kl. pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are steady), Salmonella spp. (including S. typhi), Serratia spp. (including S. marcescens), Shigella spp., Vibrio spp. (including V. cholerae), Yersinia spp. (including Y. enterocolitica).

Note: many strains of the listed microorganisms which in the presence of other antibiotics, for example, of penicillin, cephalosporins of the first generations and aminoglycosides, steadily breed are sensitive to a tseftriakson. Treponema pallidum is sensitive to a tseftriakson as in vitro, and in animal experiments. According to clinical data at primary and secondary syphilis note good efficiency of a tseftriakson.

Anaerobic pathogens of Bacteroides spp. (including some strains of V. of fragilis), Clostridium spp. (including Cl. difficile), Fusobacterium spp. (except F. mostiferum. F. varium), Pep-tococcus spp., Peptostreptococcus spp. Note: some strains of many Bacteroides spp. (for example, V. of fragilis), the developing beta lactamazu, are steady against a tseftriakson. It is necessary to apply the disks containing цефтриаксон as it is shown that in vitro certain strains of pathogens can be steady against classical cephalosporins to definition of sensitivity of microorganisms.

Pharmacokinetics. At parenteral administration цефтриаксон well gets into fabrics and liquids of an organism. At healthy adult examinees of a tseftriakson it is characteristic long, about 8 hours, an elimination half-life. The areas under a curve concentration - time in blood serum at intravenous and intramuscular administration match. It means that bioavailability of a tseftriakson at intramuscular introduction makes 100%. At intravenous administration цефтриаксон quickly diffuses in intersticial liquid where the bactericidal action concerning pathogens, sensitive to it, keeps within 24 hours.

Tseftriakson reversibly contacts albumine and this binding in inverse proportion to concentration: for example, at concentration of drug in blood serum less than 100 mg/l linkng of a tseftriakson with proteins makes 95%, and at concentration of 300 mg/l - only 85%. Thanks to lower content of albumine in intersticial liquid concentration of a tseftriakson in it is higher, than in blood serum. The elimination half-life at healthy adult examinees makes about 8 hours. At newborns up to 8 days and at elderly people 75 years an average elimination half-life approximately twice more are more senior. At adult 50-60% of a tseftriakson 40-50% - also in not changed form with bile are allocated in not changed form with urine, and. Under the influence of an indestinal flora цефтриаксон turns into an inactive metabolite. At newborns about 70% of the entered dose it is allocated with kidneys.

At a renal failure or at liver pathology at adults the pharmacokinetics of a tseftriakson almost does not change, the elimination half-life is extended slightly. If function of kidneys is broken, allocation with bile increases and if liver pathology takes place, then allocation of a tseftriakson kidneys amplifies.

Penetration into cerebrospinal fluid: at newborns and at children at a meninx inflammation цефтриаксон gets into liquor, at the same time in case of bacterial meningitis on average 17% of concentration of drug in blood serum diffuse in medullispinal liquid that is about 4 times more, than at aseptic meningitis. In 24 hours after intravenous administration of a tseftriakson in a dose of 50-100 mg/kg of body weight concentration in medullispinal liquid exceeds 1,4 mg/l. At adult patients with meningitis in 2-25 hours after introduction of a tseftriakson in a dose of 50 mg/kg of body weight concentration of a tseftriakson repeatedly exceeded that minimum oppressing dose which is necessary for suppression of the pathogens which are most often causing meningitis

Indications to use:

The infections caused by activators, sensitive to a tseftriakson: sepsis, meningitis, infections of an abdominal cavity (peritonitis, inflammatory diseases of digestive tract, biliary tract), infections of bones, joints, connecting fabric, skin, an infection at patients with the lowered immunity, infections of kidneys and urinary tract, respiratory infections (including pneumonia), and also infections of ENT organs, urogenital infections (including gonorrhea). Prevention of infections in the postoperative period.

Route of administration and doses:

Drug is used intramusculary and intravenously. For adults and for children over 12 years the Average daily dose makes 1-2 g of a tseftriakson of 1 times a day or 0.5-1 g each 12 h. In hard cases or in cases of the infections caused by moderately sensitive pathogens, the daily dose can be increased to 4 g. For newborns At a one-time daily dosage the following scheme is recommended: For newborns (to two-week age): 20-50 mg/kg of body weight a day (the dose of 50 mg/kg of body weight is not recommended to be exceeded in connection with unripe fermental system of newborns). For babies and children up to 12 years.

The daily dose makes 20-75 mg/kg of body weight. Children with body weight have 50 kg and it is necessary to adhere to a dosage for adults above. It is necessary to appoint a dose more than 50 mg/kg of body weight in the form of intravenous infusion, at least, within 30 minutes. Duration of therapy Depends on the course of a disease. Meningitis At bacterial meningitis at newborns and at children the initial dose makes 100 mg/kg of body weight once a day (at most 4 g). As soon as the pathogenic microorganism was succeeded to allocate and to define his sensitivity a dose it is necessary to reduce respectively. The best results were achieved at the following terms of therapy: Activator Neisseria meningitides therapy Duration 4 days of Haemophilus mfluenzae 6 days of Streptococcus pneumoniae 7 days Sensitive Enterobacteriacease of 10 - 14 days

Gonorrhea. For treatment of the gonorrhea caused by the strains both forming, and not forming a penicillinase, the recommended dose makes 250 mg once intramusculary. Prevention in before - and the postoperative period Before the infected or presumably infected surgical interventions for the prevention of postoperative infections, depending on danger of an infection, in 30-90 minutes prior to operation is recommended single introduction of a tseftriakson in a dose of 1-2 g. Insufficiency of function of kidneys and liver.

At patients with an impaired renal function, on condition of normal function of a liver to reduce a dose of a tseftriakson there is no need. Only at insufficiency of kidneys in a preterminal stage (the clearance of creatinine is lower than 10 ml/min.) it is necessary that the daily dose of a tseftriakson did not exceed 2 g. At patients with the broken function of a liver, on condition of preservation of function of kidneys to reduce a dose of a tseftriakson also there is no need. In cases of simultaneous existence of heavy pathology of a liver and kidneys concentration of a tseftriakson in blood serum needs to be controlled regularly. At the patients subjected to a hemodialysis to change a drug dose after holding this procedure there is no need.

Intramuscular introduction. For intramuscular introduction of 1 g of drug it is necessary to part in 3,5 ml of 1% solution of lidocaine and to enter deeply into a gluteus, it is recommended to enter no more than 1 g of drug into one buttock. Lidocaine solution can never be entered intravenously! Intravenous administration For an intravenous injection of 1 g of drug needs to be parted in 10 ml of the sterile distilled water and to enter intravenously slowly within 2-4 minutes.

Intravenous infusion. Duration of intravenous infusion, at least, 30 minutes. For intravenous infusion of 2 g of powder it is necessary to part approximately in 40 ml of solution free from calcium, for example: in 0,9% chloride sodium solution, in 5% dextrose solution, in 10% solution of a dextrose, 5% fructose solution

Features of use:

At a simultaneous heavy renal and liver failure, it is regularly necessary to define concentration of drug in plasma.

At the patients who are on a hemodialysis it is necessary to watch concentration of a tseftriakson in plasma since at them the speed of its removal can decrease.

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 which disappear after cancellation are noted (even if this phenomenon is followed by pains in right hypochondrium, purpose of an antibiotic and carrying out a symptomatic treatment recommend continuation).

During treatment the ethanol use is contraindicated - disulfiramopodobny effects are possible (face reddening, a spasm in a stomach, nausea, vomiting, a headache, decrease in the ABP, tachycardia, short wind).

Despite detailed collecting the anamnesis that is the rule and for other tsefalosporinovy antibiotics, it is impossible to exclude development of an acute anaphylaxis which demands immediate therapy – at first intravenously enter Epinephrinum, then glucocorticosteroids.

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

Purpose of vitamin K can be required by the elderly and weakened patients.

Use at pregnancy and during breastfeeding. At pregnant women in 2-3 trimeter it is necessary to use drug only if the estimated advantage for mother exceeds potential risk for a fruit.

At purpose of drug in the period of a lactation it is necessary to stop breastfeeding.

Side effects:

Allergic reactions: a small tortoiseshell, a fever or fever, rash, an itch, it is rare - a bronchospasm, an eosinophilia, an erythema polymorphic exudative (including Stephens-Johnson's syndrome), a serum disease, a Quincke's disease, an acute anaphylaxis.

From the alimentary system: nausea, vomiting, diarrhea or lock, meteorism,

abdominal pains, taste disturbance, stomatitis, glossitis, pseudomembranous coloenteritis, abnormal liver function (increase in activity of "hepatic" transaminases, is more rare - an alkaline phosphatase or bilirubin, cholestatic jaundice), dysbacteriosis, pseudo-cholelithiasis of a gall bladder.

From bodies of a hemopoiesis: leukopenia, neutropenia, granulocytopenia, thrombocytopenia, hemolitic anemia, hypocoagulation, decrease in plasma blood-coagulation factors (II, VII, IX, X), lengthening of a prothrombin time.

From an urinary system: a renal failure (an azotemia, increase in content of urea in blood, an oliguria, an anury, a giperkreatininemiya, a glucosuria, a hamaturia, a cylindruria).

Local reactions: phlebitis, morbidity on the vein course, morbidity and infiltrate in the place in oil of introduction.

Others: superinfection, candidiasis, headache, dizziness, nasal bleedings.

Interaction with other medicines:

Tseftriakson and aminoglycosides possess a synergism concerning many gram-negative bacteria.

It is not compatible to ethanol.

Tseftriakson, suppressing an indestinal flora, interferes with vitamin K synthesis.

Interaction with anticoagulants, non-steroidal anti-inflammatory drugs and other inhibitors of aggregation of thrombocytes increases probability of bleeding.

At simultaneous use with "loopback" diuretics and other nefrotoksichny HP the risk of development of nephrotoxic action increases.

Pharmaceutical it is not compatible to solutions of other antibiotics; solutions, calciferous.

Contraindications:

Hypersensitivity to cephalosporins and to penicillin. First trimester of pregnancy.

With care. A hyperbilirubinemia at newborns, premature children, a renal/liver failure, the nonspecific ulcer colitis, enteritis or colitis connected using antibacterial drugs, pregnancy 2-3trimestr, the lactation period.

Overdose:

High concentration of a tseftriakson in plasma cannot be excessive are lowered by means of a hemodialysis or peritoneal dialysis. For treatment of cases of overdose symptomatic measures are recommended.

Storage conditions:

Period of validity 2 years. Not to use the List B after expiry date. In the dry, protected from light place at a temperature not above 20 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous and intramuscular administration of 1,0 g in bottles. On 10 bottles place in a cardboard pack together with the application instruction. On 50 bottles together with application instructions place a box from a cardboard with an investment of application instructions (for hospitals).