Composition, form of production and packaging
Powder for solution for iv and in / m introduction white or white with a yellowish hue; sensitive to the action of light.
ceftriaxone (in the form of the sodium salt) 1 g
Solvent: water d / and (5 ml).
Vials with a capacity of 10 ml (1) - packs cardboard.
Vials with a capacity of 10 ml (1) complete with a solvent (amp 1 pc.) - packs of cardboard.
Vials of glass with a capacity of 10 ml (1) complete with a solvent (1 pc.) - packings of cellular contour (1) - packs of cardboard.
Vials with a capacity of 10 ml (5) - packings, cellular, planimetric (1) - packs cardboard.
Glass bottles with a capacity of 10 ml (5) complete with a solvent (amp 5 pcs.) - packings of cellular contour (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
Ceftriabol is a third generation cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits the synthesis of the cell membrane, in vitro inhibits the growth of most gram-positive and gram-negative microorganisms. It is resistant to beta-lactamase enzymes (both penicillinase and cephalosporinase, produced by the majority of Gram-positive and Gram-negative bacteria). Effective against the following microorganisms:
Gram-positive aerobes : Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus B (Str. Agalactiae), Streptococcus viridans, Streptococcus bovis.
Note: Staphylococcus spp., Resistant to methicillin, is resistant to cephalosporins, including ceftriaxone. Most strains of enterococci (for example, Streptococcus faecalis) are also resistant to ceftriaxone.
Gram-negative aerobes: Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are resistant), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (including Kl. pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelhides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are resistant), 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 these microorganisms, which in the presence of other antibiotics, for example, penicillins, first-generation cephalosporins and aminoglycosides, are multiplying steadily, sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data, in the primary and secondary syphilis, a good efficacy of ceftriaxone is noted.
Anaerobic pathogens: Bacteroides spp. (including some strains of B. fragilis), Clostridium spp. (including Cl. difficile), Fusobacterium spp. (except F. mostiferum, F.varium), Peptococcus spp., Peptostreptococcus spp.
Note: some strains of many Bacteroides spp. (for example, B. fragilis), producing beta-lactamase, are resistant to ceftriaxone. To determine the sensitivity of microorganisms, it is necessary to use discs containing ceftriaxone, t. It was shown that in vitro to classical cephalosporins certain strains of pathogens can be stable.
The main pharmacokinetic parameters, other than T 1/2 , depend on the administered dose. After 1/2 h after a single IV dose of 0.5 g; 1 g; and 2 g of the drug concentration in serum are 82 mg / l. 151 mg / L and 257 mg / L, respectively. After 24 hours, the serum concentrations are 5 mg / L, 9 mg / L and 15 mg / L. After IV administration, a dose of 1 g of C max is achieved 2 hours after injection and is 81 mg / L. Bioavailability with the / m introduction is 100%. With repeated intravenous and / or injections, cumulation of the drug in the blood plasma is observed. With parenteral administration, ceftriaxone penetrates well into the tissues and body fluids.With iv introduction, ceftriaxone rapidly diffuses into the interstitial fluid, where its bactericidal action against pathogens sensitive to it persists for 24 hours. Ceftriaxone reversibly binds to albumin and this binding is inversely proportional to the concentration: for example, when the concentration of the drug in the blood serum is less than 100 mg / l binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg / l - only 85%. Due to the lower content of albumins in the interstitial fluid, the concentration of ceftriaxone in it is higher than in serum.
T 1/2 in healthy adult subjects is about 8 hours. In neonates up to 8 days and in elderly people over 75 years, the mean T 1/2 is approximately twice as large. In adults, 50-60% of ceftriaxone is excreted unchanged through the urinary system, and 40-50% is also unchanged through the gastrointestinal tract. Under the influence of intestinal flora, ceftriaxone is converted into an inactive metabolite. In neonates, approximately 70% of the administered dose is excreted by the kidneys.
With renal insufficiency or liver pathology in adults, the pharmacokinetics of ceftriaxone is almost unchanged, T 1/2 lengthens slightly. If the kidney function is impaired, the secretion with bile increases, and if liver pathology takes place, then the secretion of ceftriaxone by the kidneys increases.
Penetration into the cerebrospinal fluid: in newborns and in children with inflammation of the medullary membrane, ceftriaxone penetrates into the cerebrospinal fluid, while in the case of bacterial meningitis, on average 17% of the concentration of the drug in the blood serum diffuses into the cerebrospinal fluid, which is approximately 4 times greater than with aseptic meningitis. At 24 hours after intravenous administration of ceftriaxone in a dose of 50-100 mg / kg body weight, the concentration in the cerebrospinal fluid exceeds 1.4 mg / l. In adults with meningitis, 2 to 25 hours after the administration of ceftriaxone at a dose of 50 mg / kg body weight, the concentration of ceftriaxon was many times greater than the minimal oppressive dose that is necessary to suppress the pathogens most commonly causing meningitis.
Infections caused by susceptible to ceftriaxone pathogens:
- CNS infections (meningitis, brain abscess);
- Infections of the abdominal cavity (peritonitis, inflammatory diseases;
- infections of the digestive tract, bile ducts;
- infections of bones, joints, connective tissue, skin;
- infections in patients with low immunity (febrile neutropenia, etc.);
- Infection of the kidneys and urinary tract (acute and exacerbation of chronic pyelonephritis, pyelitis);
- respiratory tract infections (including pneumonia), as well as infections of the ENT organs;
- urogenital infections (including gonorrhea).
Prevention of infections in the postoperative period.
The drug is used in / m and / in.
For adults and for children over 12 years of age:
The average daily dose is 1-2 g of ceftriaxone 1 time / day or 0.5-1 g every 12 hours.
In severe cases or in cases of infections caused by moderately sensitive pathogens , the daily dose may be increased to 4 g.
For newborns with a single daily dosage, the following scheme is recommended:
For newborns (up to 2 weeks of age): 20-50 mg / kg of body weight per day (a dose of 50 mg / kg of body weight is not recommended because of the immature enzyme system of newborns).
For infants and children under 12 years of age: the daily dose is 20-75 mg / kg body weight.
Children with a body weight of 50 kg and above should adhere to the dosage for adults. A dose of more than 50 mg / kg body weight should be given as an IV infusion, for at least 30 minutes.
The duration of therapy depends on the course of the disease.
In bacterial meningitis in newborns and in children, the initial dose is 100 mg / kg of body weight once a day (maximum 4 g). Once it was possible to isolate the pathogenic microorganism and determine its sensitivity, the dose should be reduced. The best results were achieved with the following periods of therapy:
Causation Duration of therapy
Neisseria meningitidis 4 days
Haemophilus influenzae 6 days
Streptococcus pneumoniae 7 days
Sensitive Enterobacteriacease 10-14 days
For the treatment of gonorrhea, caused by both generative and non-penicillinase-resistant strains, the recommended dose is 250 mg once-monthly.
Prevention in the pre- and postoperative period
Before infected or suspected infected surgical interventions to prevent postoperative infections, depending on the risk of infection, one-time administration of ceftriaxone in a dose of 1 -2 g is recommended 30-90 minutes prior to surgery.
In patients with impaired renal function , under the condition of normal liver function, a dose of Ceftriaabol is not necessary to reduce. Only if the kidney is deficient in the preterminal stage, it is necessary that the daily dose of ceftriaabol does not exceed 2 g.
In patients with impaired liver function , if the function of the kidneys is maintained, the dose of the drug should not be reduced.
In cases of simultaneous presence of severe pathology of the liver and kidneys, the concentration of ceftriaxone in serum should be monitored regularly. In patients undergoing hemodialysis, the dose of the drug after this procedure is not necessary to change.
For the / m introduction, 1 g of the drug should be diluted in 3.5 ml of a 1% solution of lidocaine and inserted deep into the gluteal muscle, it is recommended to inject no more than 1 g of the drug into one buttock. A solution of lidocaine can never be injected in / in!
For intravenous injection, 1 g of the drug must be diluted in 10 ml of sterile distilled water and injected iv slowly for 2-4 minutes.
The duration of IV infusion is at least 30 minutes. For intravenous infusion, 2 g of powder should be diluted in approximately 40 ml of calcium free solution, for example: in 0.9% solution of sodium chloride, in a 5% dextrose solution, in a 10% solution of dextrose, 5% solution of fructose.
Allergic reactions: urticaria, chills or fever, rash, itching, rarely bronchospasm, eosinophilia, erythema, polymorphic exudative (including Stevens-Johnson syndrome), serum sickness, angioedema, anaphylactic shock.
On the part of the digestive system: nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, taste disturbance, stomatitis, glossitis, pseudomembranous enterocolitis, impaired liver function (increased activity of hepatic transaminases, less often - alkaline phosphatase, bilirubin, cholestatic jaundice), pseudo-cholelithiasis of the gallbladder ("Sludge" -syndrome), a dysbacteriosis.
On the part of the hematopoiesis: leukopenia, leukocytosis, neutropenia, granulocytopenia, lymphopenia, thrombocytosis, thrombocytopenia, hemolytic anemia, basophilia, hypocoagulation, decrease in plasma clotting factor concentration (II, VII, IX, X), prolongation of prothrombin time.
On the part of the urinary system: renal dysfunction (azotemia, increased urea in the blood, hypercreatininaemia, glycosuria, cylindruria, hematuria), oliguria, anuria.
Local reactions: phlebitis, soreness along the vein, soreness and infiltration at the site of the / m introduction.
Other: headache, dizziness, nosebleeds, candidiasis, superinfection.
- Hypersensitivity to cephalosporins, penicillins and carbapenems;
- I trimester of pregnancy;
With caution: hyperbilirubinemia in newborns, premature babies, renal / hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs, pregnancy II-III trimesters.
PREGNANCY AND LACTATION
The drug is contraindicated in the first trimester of pregnancy. Use with caution in pregnancy in the II-III trimesters.
The drug is contraindicated during lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use with caution in renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use with caution in liver failure.
APPLICATION FOR CHILDREN
Use with caution in newborns and premature infants.
With simultaneous severe renal and hepatic insufficiency, the concentration of the drug in the plasma should be regularly determined.
In patients who are on hemodialysis, it is necessary to monitor the concentration of ceftriaxone in the plasma, tk. they can decrease the rate of its excretion. With long-term treatment, it is necessary to regularly monitor the picture of peripheral blood, indicators of the functional state of the liver and kidneys. In rare cases, with ultrasound examination of the gallbladder, blackouts are noted that disappear after cancellation (even if this phenomenon is accompanied by pain in the right hypochondrium, recommend continued antibiotic prescription and symptomatic treatment). During treatment, the use of ethanol is contraindicated - disulfiramoid-like effects are possible (reddening of face, spasm in the stomach, nausea, vomiting, headache, lowering of blood pressure, tachycardia, dyspnea).
Despite the detailed history, which is the rule for other cephalosporin antibiotics, we can not exclude the possibility of developing an anaphylactic shock, which requires immediate therapy - first I / O injected epinephrine, then GCS.
In vitro studies have shown that, like other cephalosporin antibiotics, ceftriabol is able to displace bilirubin bound to serum albumin. Therefore, in newborns with hyperbilirubinemia and, especially, in preterm infants, the use of ceftriaabol requires even greater caution.
Elderly and debilitated patients may require the appointment of vitamin K.
Excessively high concentrations of ceftriaxone in plasma can not be reduced by hemodialysis or peritoneal dialysis. Symptomatic measures are recommended for the treatment of overdose cases.
Ceftriaxone and aminoglycosides have a synergistic effect on many Gram-negative bacteria. Incompatible with ethanol.
Nonsteroidal anti-inflammatory drugs and other inhibitors of platelet aggregation increase the likelihood of bleeding. With simultaneous use with "loop" diuretics and other nephrotoxic drugs, the risk of developing nephrotoxic action increases.
Pharmaceutically incompatible with solutions containing other antibiotics.
TERMS OF RELEASE FROM PHARMACY
According to doctor's prescription.
TERMS AND CONDITIONS OF STORAGE
List B. In a dry, the dark place at a temperature of no higher than 25 В° C. Keep out of the reach of children.
Shelf life 2 years. Do not use after expiration date