Цефтриабол®

General characteristics. Structure:

Active ingredient: 1,0 g of a tseftriakson of sodium (in terms of цефтриаксон).
Tsefalosporinovy antibiotic of the III generation of a broad spectrum of activity for parenteral administration.

Pharmacological properties:

Pharmacodynamics. The Tsefalosporinovy antibiotic of the III generation of a broad spectrum of activity for parenteral administration. Bactericidal action is caused by irreversible linkng with bacterial transpeptidases that leads to disturbance of the final stages of synthesis of a cell wall of microorganisms. Differs in resistance to action of the majority beta лактамаз gram-negative and gram-positive microorganisms.

Tseftriakson is active concerning the following microorganisms:
- gram-positive aerobes - Staphylococcus aureus (including the strains producing penicillinases), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. viridans groups;
- gram-negative aerobes - Acinetobacter calcoaceticus, Borrelia burgdorferi, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including strains producers beta лактамаз, steady against ampicillin), Haemophilus parainfluenzae, Klebsiella spp. (including Klebsiella pneumoniae) Moraxella catarrhalis (including strains producers beta лактамаз), Morganella morganii, Neisseria gonorrhoeae (including the strains which are producing and not producing a penicillinase), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (including Serratia marcescens), Pseudomonas aeruginosa (separate strains);
- anaerobe bacterias - Bacteroides fragilis, Clostridium spp. (except C. difficile), Peptostreptococcus spp.
Has activity of in vitro concerning the majority of strains of the following microorganisms though clinical value of it is unknown: Citrobacter diversus, Citrobacter freundii, Providencia spp. (including Providencia rettgeri), Salmonella spp. (including S. typhi), Shigella spp., Streptococcus agalactiae, Bacteroides bivius, Bacteroides melaninogenicus.

Many strains of the listed above gram-positive and gram-negative microorganisms steady against cephalosporins I-II of generations, natural and semi-synthetic penicillin, aminoglycosides are sensitive to a tseftriakson.

Are steady against a tseftriakson: metitsillinoustoychivy Staphylococcus spp., Enterococcus faecalis and Enterococcus faecium, Listeria monocytogenes.
 
Pharmacokinetics. The key pharmacokinetic parameters, except an elimination half-life (Т½), depend on the entered dose. In ½ hours after single intravenous (in/in) introductions of 0,5 g, 1 g and 2 g of drug of concentration in blood serum make 82 mg/l, 151 mg/l and 257 mg/l, respectively. In 2 hours of concentration decrease, respectively, to 48 mg/l, 67 mg/l and 154 mg/l. In 24 hours serumal concentration make 5 mg/l, 9 mg/l and 15 mg/l. After intramuscular introduction of a tseftriakson (in oil) in a dose of 0,5 g and 1 g the maximum concentration are observed in 2 hours after an injection and make 38 mg/l and 81 mg/l, respectively. Bioavailability at introduction in oil makes 100%.
 
At repeated in/in or introductions in oil cumulation of drug in a blood plasma is observed. Later in/in or introductions in oil цефтриаксон quickly gets into various liquids and body tissues in the concentration exceeding the minimum overwhelming concentration (MOC) for sensitive microorganisms. Within at least 24 hours after introduction of concentration above MPK are observed in lungs, heart, bile and bilious ways, a liver, palatine tonsils, a middle ear, a mucous membrane of a nose, bones, and also spinal, synovial, pleural, peritoneal liquids and a secret of a prostate.
 
Well gets into cerebrospinal fluid at an inflammation of a meninx. In small concentration gets into breast milk. Tseftriakson reversibly contacts plasma albumine, and extent of binding decreases with concentration growth, reaching 95% at concentration of an antibiotic less than 25 mg/l and decreasing to 85% at concentration of 300 mg/l.

Tseftriakson has a double way of removal. From 33% to 67% of the entered dose it is allocated with kidneys in not changed form. Other part is excreted in not changed view with bile, turns in intestines into inactive metabolites and is allocated through intestines. Concentration of a tseftriakson in bile many times over exceed serumal.
 
Т½ the tseftriaksona at adults with normal function of a liver and kidneys makes from 5,8 to 6,7 h Т½ of liquid of a middle ear makes 25 h. At newborns through kidneys about 70% of the entered dose are removed. At an abnormal liver function and kidneys the pharmacokinetics of a tseftriakson changes slightly: if function of kidneys is broken, release of drug with bile increases; on the contrary, at an abnormal liver function elimination through kidneys increases. At patients 75 years Т½ are more senior raises by 2-3 times.

Indications to use:

The bacterial infections caused by activators, sensitive to a tseftriakson: bacterial septicaemia, bacterial meningitis; infections of abdominal organs (including peritonitis); infectious and inflammatory diseases of digestive tract and biliary tract, including cholecystitis, a cholangitis, an empyema of a gall bladder), infectious and inflammatory diseases of bodies of a small pelvis (including a salpingo-oophoritis, an endometritis, a parametritis, a pelviperitonitis); acute average otitis; lower respiratory tract infections, including pneumonia, pleura empyema, abscess of lungs; infections of bones and joints, including infectious (septic) arthritis, osteomyelitis; infections of skin and soft tissues (including contaminated wounds and burns); the uncomplicated and complicated infections of kidneys and urinary tract (acute and an exacerbation of chronic pyelonephritis, a pyelitis); uncomplicated gonorrhea, Lyme's disease.

Infectious diseases at persons with the weakened immunity.

It is shown for a perioperatsionny antibiotikoprofilaktika.

Route of administration and doses:

Not to use the solutions containing calcium ions for cultivation of Tseftriabola®.

Цефтриабол® it can be entered intravenously and intramusculary. In need of single introduction in a dose more than 1 g, and also in/in a way of introduction are preferable to treatment of heavy infections.

At adults and at children with a body weight of 50 kg and above Tseftriabol® it is entered in a dose from 1 to 2 g of 1 times a day (or on 0,5-1 g each 12 h), depending on a form and weight of an infection. In hard cases the dose can be increased, but should not exceed 4 g/days.

At Lyme's disease (tick-borne borreliosis) the daily dose at children and adults makes 50 mg/kg (the maximum daily dose - 2 g); treatment duration - 14 days.

For treatment of uncomplicated gonorrhea цефтриаксон enter in a dose 250 mg intramusculary once.

For a perioperatsionny antibiotikoprofilaktika of infectious complications at adults of 1 g of a tseftriakson enter in/in in 30-90 min. prior to operation. At operations on thick and a rectum it is recommended simultaneous (but separate!) introduction of 2,0 g of a tseftriakson and drug from group 5 of nitroimidazoles.

The newborn enter in a dose from 20 to 50 mg/kg of 1 times a day, or divide a daily dose into two introductions. The maximum dose makes 50 mg/kg/days.

For treatment of infections of skin and soft tissues the recommended daily dose at children - 50-75 mg/kg, once a day or divided into two receptions (each 12 h). The total daily dose should not exceed 2 g.

For treatment of bacterial meningitis at children appoint in a daily dose 100 mg/kg (but no more than 4 g/days) which is entered into 1 time a day, or the daily dose is divided into two in/in introductions (each 12 h). The recommended duration of therapy of 7-14 days.

For treatment of acute average otitis of Tseftriabol® enter in oil once in a dose of 50 mg/kg (no more than 1 g).

For treatment of other infections at children the recommended daily dose of a tseftriakson makes 50-75 mg/kg of body weight which is entered 1 time a day or divide into 2 receptions (each 12 h). The total daily dose should not exceed 2 g.

Children with body weight have more than 50 kg and apply doses to adults above.

Treatment of Tseftriabolom® has to continue at least 2 more days after disappearance of symptoms and symptoms of an infection. The course of treatment usually makes 4-14 days; at the complicated infections more long introduction can be required. At treatment of the infections caused by Streptococcus pyogenes, duration of therapy has to make not less than 10 days.

Patients with moderately expressed renal failures have no need to reduce a dose of a tseftriakson on condition of normal function of a liver. The daily dose of Tseftriabola® should not exceed 2 g only at patients with clearance of creatinine less than 10 ml/min. The patients who is on a hemodialysis do not need to enter an additional dose of a tseftriakson after dialysis session. However it is necessary to control concentration of a tseftriakson in blood serum regarding possible dose adjustment.

Patients with an abnormal liver function have no need to reduce a dose of a tseftriakson on condition of normal function of kidneys.

At patients with a renal liver failure the daily dose of Tseftriabola® should not exceed 2 g without definition of concentration of drug in a blood plasma.

Rules of preparation of solutions.
 Intramuscular introduction. For intramuscular introduction of 2,0 g of drug it is necessary to part in 7,0 ml of 1% solution of lidocaine and to enter deeply into gluteuses. It is recommended to enter no more than 1 g of drug into one buttock. Solution of lidocaine cannot be entered intravenously!

Intravenous administration. ÛÑõÔÓ¿áí«½® 2,0 g enter a type of intravenous infusion. For this purpose 2,0 g of drug dissolve in not less than 50 ml of solution, free from calcium: 0,9% chloride sodium solution, in 5% or 10% dextrose solution. The received solution is entered slowly, not less than 30 min.

Features of use:

In rare instances against the background of or after therapy tseftriaksony at ultrasound examination of a gall bladder the acoustic shadows taken for concrements are found and/or the clinic of cholelithiasis develops. The phenomena are caused by precipitation and formation of a deposit of connections of a tseftriakson with calcium in a gall bladder. It is necessary to cancel an antibiotic and to carry out a symptomatic treatment.

At the infections caused by aerobic-anaerobic flora (peritonitis, abscess of lungs, an empyema of a pleura, an infection of bodies of a small pelvis) it is recommended to combine цефтриаксон with the drugs used at a mephitic gangrene (for example, from group 5 of nitroimidazoles). At multi-infections and a probable etiological role of chlamydias and mycoplasmas combinations of a tseftriakson with tetracyclines or macroleads are recommended.

At a simultaneous heavy renal and liver failure it is regularly necessary to define concentration of drug in plasma. Patients with a liver failure have a recommended daily dose of a tseftriakson - no more than 2 g.

At patients with vitamin K metabolism disturbance (for example, a liver failure) it is necessary to control a prothrombin time regularly. In case of lengthening of a prothrombin time to or during use of a tseftriakson it is necessary to appoint vitamin K in a dose of 10 mg a week.

With care it is necessary to use цефтриаксон at the persons having associated diseases of intestines, especially colitis. When developing diarrhea during treatment tseftriaksony it is necessary to show vigilance in view of possible development of pseudomembranous colitis. If the diagnosis an antibiotic - the associated diarrhea or pseudomembranous colitis is established, it is necessary to stop introduction of a tseftriakson and to appoint the corresponding treatment.

As well as in case of other antibiotics, use of a tseftriakson can lead to colonization by insensitive microflora and to development of superinfection. At prolonged treatment it is regularly necessary to control a pattern of peripheral blood, indicators of a functional condition of a liver and kidneys.

Side effects:

Allergic reactions: fever or fever, rash, itch.

From a nervous system: headache, dizziness.

From the alimentary system: nausea, vomiting, diarrhea, pseudomembranous colitis.

From system of blood and bodies of a hemopoiesis: anemia (including hemolitic), eosinophilia, leukopenia, neutropenia, thrombocytopenia, lymphopenia, thrombocytosis.

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 alkaline phosphatase, hyperbilirubinemia, giperkreatininemiya, increase in concentration of urea, existence of a deposit in urine.

Others: the increased sweating, blood "inflows".

Undesirable reactions with a frequency less than 0,1%: abdominal pain, an agranulocytosis, an allergic pneumonitis, an anaphylaxis, a basophilia, a bronchospasm, colitis, dyspepsia, nasal bleeding, abdominal distention, the pseudo-cholelithiasis phenomena with or without the corresponding symptomatology which pass independently after drug withdrawal, a glucosuria, a .gematuriya, jaundice, a leukocytosis, a lymphocytosis, a monocytosis, a nephrolithiasis, heartbeat, spasms, a serum disease.

Post-marketing experience: stomatitis, a glossitis, an oliguria, rash, allergic dermatitis, a small tortoiseshell, hypostasis, a multiformny erythema, Stephens's syndrome -
 
Johnson, Lyell's disease.

Interaction with other medicines:

Let's combine with the following infusion solutions: 0,9% solution of sodium of chloride, 5% and 10% dextrose solutions, the solution containing 0,9% of sodium of chloride and 5% of a dextrose, the solution containing 0,45% of sodium of chloride and 5% of a dextrose, 6% dextran solution in 5% solution of glucose, 6-10% solutions of hydroxyethylated starch, 5% fructose solution. Not to use as solvent and not to add цефтриаксон to the solutions containing calcium ions (Ringer and Hartman's solution).

Pharmaceutical it is incompatible with Vancomycinum, flukonazoly and aminoglycosides. At simultaneous use they should not be mixed in one syringe or one infusional environment; at introduction in oil to enter into different body parts; at intravenous administration it is recommended to enter separately, observing the sequence, with as it is possible a big time interval between injections (infusions), or to use separate intravenous catheters. In vitro between chloramphenicol and tseftriaksony is observed antagonism.

The risk of bleedings increases at a concomitant use of a tseftriakson with non-steroidal anti-inflammatory drugs and other inhibitors of aggregation of thrombocytes.

At simultaneous use with "loopback" diuretics and aminoglycosides the risk of a renal failure is minimum.

Contraindications:

Hypersensitivity to a tseftriakson, other tsefalosporinovy antibiotics, penicillin, karbapenema; a hyperbilirubinemia at newborns; the newborn to whom it is shown in/in administration of the solutions containing ^Sa2+, pregnancy, the lactation period.

With care: at premature newborns; at a renal liver failure of an iila; nonspecific ulcer colitis; the colitis connected using antibacterial medicines (in the anamnesis).

Use ^{of Tseftriabola®} for pregnant women perhaps in cases when the estimated advantage for mother exceeds potential risk for a fruit, and has to be carried out under observation of the specialist. For treatment tseftriaksony breastfeeding should be stopped.

Overdose:

Symptoms: nausea, vomiting, diarrhea, confusion of consciousness, spasm. In case of overdose decrease in concentration of a tseftriakson cannot be reached by means of haemo - and peritoneal dialysis. The specific antidote is absent.

Treatment, generally symptomatic.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

On 1,0 g of active agent in bottles glass with a capacity of 10 ml.

As solvent "Water for injections" in ampoules of 10 ml is used (or 2 ampoules of 5 ml).

- One bottle with drug and the application instruction in a pack from a cardboard

- One bottle with drug, one ampoule with solvent and the application instruction in a pack from a cardboard

- One bottle with drug and one ampoule with solvent, packed in a blister strip packaging from the polyvinyl chloride film and aluminum foil varnished or without foil. One blister strip packaging and the application instruction in a pack from a cardboard

- Five bottles with drug in a blister strip packaging from the polyvinyl chloride film and aluminum foil varnished or without foil. One blister strip packaging and the application instruction in a pack from a cardboard

- Five bottles with drug and five ampoules with solvent packed in a blister strip packaging from the polyvinyl chloride film and aluminum foil varnished or without foil.

- One blister strip packaging with drug, one planimetric packaging with solvent and the application instruction in a pack from a cardboard