Рharmacological properties
Ceftriaxone – a semisynthetic antibiotic of group A beta – lactams, cephalosporins III generation, has a bactericidal effect. The mechanism of action is associated with inhibition of the activity of the enzyme transpeptidase, a violation of the biosynthesis of the cell wall peptidoglycan of microorganisms. The drug has a broad spectrum of activity: active in the relation-Research Institute of aerobic gram-positive microorganisms: facultative anaerobes – Staphylo-coccus aureus (including penitsillinazoobrazuyuschie strains), Staphylococcus epidermidis, Streptococcus pneumoniae, ß-hemolytic streptococci group A (S.pyogenes), streptokok-ki group B (S.agalactiae), Streptococcus viridans, Streptococcus bovis, Streptococcus neenterokokkovye group D; Gram-negative microorganisms: Escherichia coli, Haemophilus influenzae, H.rarainfluenzae, Klebsiella species (including Kb pneumoniae.), Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia, Salmonella (including S.typhy), Serratia spp. (Including S.marcescens), Shigella, Versinia (including Y.enterocolitica); microaerophiles – Treponema pallidum; aerobes – Neisseria gonorrheae (including penitsillinazoobrazuyuschih strain), Neisseria meningitides, Pseudomonas aeruginosa; obligate anaerobes, Bacteroides species (including some strains B.Fragilis), Clostridium (but most strains of C. difficile is resistant), Peptococcus, Peptostreptococcus, Fusobacterium (including F.mortiferum and F.varium). The drug is prescribed for microbial resistance to other drugs cephalosporin, aminoglycosides, penicillins, etc.

Pharmacokinetics
The drug is not administered orally, because it breaks down quickly under the influence of digestive juice. After intramuscular (i / m) is absorbed quickly and completely. Bioavailable-ness is 100%. The drug is reversibly bound to plasma albumin (85-95%), with in elevated blood levels reduced protein binding. The drug is not hydro-lizuetsya R-plasmid beta-lactamases and most hromosomnoobuslovlennyh fine-tsillinaz cephalosporinase and can act on the multidrug strains tolerant to penicillins and cephalosporins I and II generation and aminoglycosides. Acquired resistance is caused by certain strains of bacteria produce beta-lactamase, which inactivates ceftriaxone. The drug has a high degree of stability and prolonged half-life (T1 / 2). After the / m of the maximum concentration (Cmax) in plasma is determined by 1.5-2-3 hours and is at a dose of 1 g -80 mg / l; by intravenous (i / v), respectively administered 30 minutes max of 100-150 mg / l. A stable concentration is reached after 4 hours. The minimum concentration of antimicrobial found in the blood over 24 hours. Ceftriaxone is well distributed in tissues and body fluids (synovial, peritoneal, interstitial), enters the cerebrospinal fluid, the drug is also found in the bone tissue at an inflammation of the meninges, it passes through the placenta. The drug in a small amount excreted in breast milk (3.4%). In unmodified form (50-65%) is excreted by the kidneys within 48 hours, about 40% – in the bile. T1 / 2 when administered in doses of 0,15-3,0 g 6-9 hours, volume of distribution (Vd) -5,78-13,5 l plasma clearance – 0,58-1,45 l / h , 0,32- renal clearance of 0.73 l / h. In the gut microflora under the influence of the drug is converted to an inactive metabolite. T ½ an average of 8 hours. In children, the first 8 days of life, as well as in patients older than 75 years T1 / 2 is extended to 16 hours. With the lack of renal and hepatic excretion slows down. Cumulative effect is possible.

Indications
The drug is prescribed for the treatment of infectious diseases caused by susceptible to non-mu strains of microorganisms: infections of the lower respiratory tract (pneumonia, bronchitis, lung abscess, empyema), ENT infections, infectious diseases of the kidneys and urinary organs (pyelitis, cystitis, acute and chronic pyelonephritis, prostatitis, epididymitis), infectious diseases of the skin and soft tissues, including bacterial streptococcal, meningitis, infectious diseases of bones and joints, peritonitis, inflammation of the gall bladder, gastrointestinal infections, uncomplicated gonorrhea and other infections, sexually transmitted infections ( chancroid and syphilis), Lyme disease (spirochetosis), typhoid fever, salmonellosis, salmonellonositelstva. The drug is also used to prevent infections occurring after surgical procedures.

Dosing and Administration
The drug is administered / o or w / w. For the / m in order to eliminate pain at the intro- Denia drug is dissolved in a 1% lidocaine solution in the following ratio: contents of the vial with 0.5 g dissolved in 1 ml of 2% lidocaine with 1 g – in 5.3 ml . Possible utilization of the sterile water for injection.
For on / in the preparation is dissolved in sterile water for injection in the following relation-fighting: vial contents with 0.5 g dissolved in 5 ml of solvent to 1 g – 10 ml. Adults and children over 12 years prescribed in a daily dose of 1-2 grams (1 administered once a day or half a dose of 2 times a day). In severe cases, the daily dose is about 4 g, which is administered in 2 divided doses at intervals of 12 hours. To prevent postoperative complications administered once 2.1 g (depending on the degree of danger of infection) 30-90 minutes prior to surgery. Patients with impaired renal function dose adjustment is required only in severe renal insufficiency (creatinine clearance (CC) of less than 10 ml / min).
For the elderly doses correspond to doses for adult patients. With Neos complications gonorrhea once in / injected 0.25 g of the drug.
The daily dose of the drug for infants (up to 2 weeks) and preterm infants is 20-50 mg / kg body weight. For children from 2 weeks to 12 years, the daily dose is 20-80 mg / kg of body weight, 2 administration. The on / in a dose above 50 mg / kg body weight children apply the drug-was fractionally, with intervals between doses of at least 30 minutes.
The duration of treatment depends on the nature and severity of the pathological-ray process, and determined, in addition, these bacteriological studies. Typically, the duration of treatment is 4-14 days. But in severe infections may require longer therapy. For most infectious diseases treatment lasts for at least another 48-72 hours after the disappearance of symptoms and confirmation of the effect of the results of bacteriological analysis.

Side effects
Before the drug can occur allergic reactions (rash, itching, eozi-nofiliya, serum sickness, bronchospasm, erythema multiforme exudative, anaphylactic reactions, in rare cases – anaphylactic shock), stomatitis, glossitis, and on the part of the digestive tract are possible: nausea, vomiting , loss of taste, abdominal pain, goiter, superinfection, pseudomembranous colitis. Subject to change peripheral blood neutropenia, lymphopenia, leucopenia, thrombocytopenia, rarely – hemolytic anemia, in some cases, reduced plasma levels of serum factors (II, VII, IX, X), the prothrombin time is prolonged; observed nosebleeds, developed cholestatic jaundice, urinary increased creatinine level, there are cylinders, oliguria, anuria, biochemical changes (increase in liver transaminases and bilirubin in blood plasma), acute renal failure is possible, arrhythmia, headache, or infiltration into the site the introduction, in some cases – phlebitis or thrombophlebitis with a / in the introduction.

Drug interactions

When used in combination with aminoglycosides due to increased synergy ef ciency with respect to Gram-negative microorganisms, but is necessary to choose their optimal doses. NSAIDs, antiplatelet agents increase the possibility of bleeding, loop diuretics and nephrotoxic drugs (aminoglycosides, polymyxin B) cause Naru-shenie renal function. The solution of the drug should not be mixed or administered simultaneously with other antimicrobial drugs or solutions in connection with the pharmaceutical nesovmes-reversibility.

Special instructions

With the combination of severe renal and hepatic insufficiency, and in patients on hemodialysis should be regular monitoring of the concentration of drug in plasma.

With long-term treatment should be regularly monitored picture peripheral Cro-vie, the indicators of the functional state of the liver and kidneys.

In rare cases, there are blackout (precipitates the calcium salt of ceftriaxone) ultrasound of the gall bladder, which disappear Paulsen discontinuation of treatment. With the development of symptoms or signs indicating a possible gallbladder disease, or in the presence of ultrasound – “sludge-phenomenon” signs should stop administering the drug.

In applying the drug described rare cases of pancreatitis that developed, probably due to biliary obstruction. The majority of patients had risk factors for biliary tract-standing (prior therapy with heavy accompanying Zabolev-tion, total parenteral nutrition); at the same time we can not exclude the role of the image of starter-tion of precipitates in the biliary tract under the influence of Ceftriaxone.

In applying the drug described rare cases of changes in prothrombin time. Pa-tients with a deficiency of vitamin K (a violation of the synthesis of malnutrition) may require monitoring of prothrombin time and purpose of vitamin K (10 mg per week) with an increase in prothrombin time prior to or during therapy. There are cases of fatal reactions as a result of deposition of ceftriaxone – 2+ calcium precipitates in the lungs and kidneys of neonates. Theoretically, there is a possibility of interaction of ceftriaxone with calcium-containing solutions for intravenous administration and other age groups of patients, so Ceftriaxone must not be mixed with calcium-containing solutions (including for parenteral nutrition). The interval between administration of ceftriaxone and katsy containing solutions should not be less than 48 hours. In the treatment of ceftriaxone may experience false positive Coombs test, tests for galactosemia, the determination of glucose in the urine (glycosuria is recommended to determine only by enzymes) When i / m injection injected deep in the upper outer square of the gluteus maximus. In patients with severely impaired hepatic and renal function the dose reduced. For patients with CC less than 10 mL / E daily dose of an antibiotic should not exceed 2 years

Use of the drug during pregnancy is possible only in cases where the alleged May-benefit to the mother outweighs the potential risk to the fetus or child. When needed-Mosty appointment during lactation should decide the issue of stopping breast-feeding of.

Perhaps the emergence of drug-resistant microorganisms and the development of superinfection.

Caution must be exercised with concomitant administration of “loop” diuretinov (furosemide, etc.)

When hypertension and disruption of water – electrolyte balance should be counter-lated sodium content in the plasma. With prolonged use is necessary tsitologiche-mechanical study to determine the dysbiosis.

Precautions: appoint newborns with hyperbilirubinemia who are prone to allergies, reactions.

Studies to assess the impact of the drug on the ability to drive sredst-you and other classes of potentially hazardous activities that require increased concentration-term attention and psychomotor speed reactions, have been conducted.

The drug should be stored out of reach of children and do not use after the expiration date.

Overdose
Symptoms: dizziness, paresthesia, headache, convulsions
Treatment: symptomatic. Hemodialysis and peritoneal dialysis are not effective.

Contraindications
Increased sensitivity to antibiotics belonging to the class of cephalosporin and penicillin-ne, as well as (in / m introduction) to lidocaine. Renal failure, Zabo-Levani gastrointestinal tract in history, particularly ulcerative colitis or enteritis, pregnant-ness, lactation.