Ceftriaxone | Ceftriaxone bottle, 1 g

Pharmacological action

Pharmacotherapeutic group: antibiotic, cephalosporin

ATX code [J01DA13].

Pharmacological properties

Ceftriaxone is a third-generation cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits cell membrane synthesis, and in vitro inhibits the growth of most Gram-positive and Gram-negative microorganisms. Ceftriaxone is resistant to beta-lactamase enzymes (both penicillinase and cephalosporinase produced by most Gram-positive and Gram-negative bacteria). In vitro and in clinical practice, ceftriaxone is usually effective against the following microorganisms:

Gram-positive:

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus V (Str. bovis.

Note: Staphylococcus spp., resistant to methicillin, is resistant to cephalosporins, including ceftriaxone. Most enterococcal strains (e.g. Streptococcus faecalis) are also resistant to ceftriaxone.

Gram-negative:

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 shigelloides, 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, multiply steadily, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone both in vitro and in animal experiments. According to clinical data, with primary and secondary syphilis, a good efficacy of ceftriaxone is noted.

Anaerobic pathogens:

Bacteroides spp. (including some strains of B. fragilis), Clostridium spp. (including CI. difficile), Fusobacterium spp. (except F. mostiferum. F. varium), Peptococcus spp., Peptostreptococcus spp.

Note: Some strains of many Bacteroides spp. (e.g. B. fragilis) that produce beta-lactamase are resistant to ceftriaxone. To determine the sensitivity of microorganisms, it is necessary to use disks containing ceftriaxone, since it is shown that in vitro certain strains of pathogens can be resistant to classical cephalosporins.

Pharmacokinetics:

With parenteral administration, ceftriaxone penetrates well into tissues and body fluids. In healthy adult subjects, ceftriaxone is characterized by a long, about 8 hours, half-life. The area under the concentration-time curve in the blood serum coincides with intravenous and intramuscular administration. This means that the bioavailability of ceftriaxone for intramuscular administration is 100%. With intravenous administration, ceftriaxone rapidly diffuses into the interstitial fluid, where it retains its bactericidal action against pathogens sensitive to it for 24 hours.

The elimination half-life in healthy adult subjects is about 8 hours. In newborns up to 8 days old and in older people over 75 years, the average half-life is approximately twice as long. In adults, 50-60% of ceftriaxone is excreted in unchanged form with urine, and 40-50% - also in unchanged form with bile. Under the influence of the intestinal flora, ceftriaxone turns into an inactive metabolite. In newborns, approximately 70% of the administered dose is excreted by the kidneys. With kidney failure or liver pathology in adults, the pharmacokinetics of ceftriaxone is almost unchanged, the elimination half-life is slightly increased. If renal function is impaired, excretion with bile increases, and if liver pathology occurs, then excretion of ceftriaxone by the kidneys increases.

Ceftriaxone binds reversibly 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, the binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg / l - only 85%. Due to the lower albumin content in the interstitial fluid, the concentration of ceftriaxone in it is higher than in blood serum.

Penetration into the cerebrospinal fluid: In infants and children with inflammation of the meninges, ceftriaxone penetrates the cerebrospinal fluid in the case of bacterial meningitis, an average of 17% of the concentration of the drug in the blood serum diffuses into the cerebrospinal fluid, which is about 4 times more than with aseptic meningitis. 24 hours after the intravenous administration of ceftriaxone at a dose of 50-100 mg / kg body weight, the concentration in the cerebrospinal fluid exceeds 1.4 mg / l. In adult patients with meningitis, 2–25 hours after the administration of ceftriaxone at a dose of 50 mg / kg body weight, the concentration of ceftriaxone was many times higher than the minimum inhibitory dose necessary to suppress the pathogens that most often cause meningitis.

Indications

Infections caused by ceftriaxone-sensitive pathogens: sepsis, meningitis, abdominal infections (peritonitis, inflammatory diseases of the gastrointestinal tract, biliary tract), infections of bones, joints, connective tissue, skin, infection in patients with reduced immune function system, kidney and urinary tract infections, respiratory tract infections, especially pneumonia, as well as ear, throat and nose infections, genital infections, including gonorrhea. Prevention of infections in the postoperative period.

Contraindications

Hypersensitivity to cephalosporins and penicillins. The first trimester of pregnancy.

Special instructions

Despite a detailed history taking, which is also the rule for other cephalosporin antibiotics, the possibility of anaphylactic shock, which requires immediate treatment, cannot be ruled out - adrenaline is then administered first followed by glucocorticoids.

Sometimes, with an ultrasound examination of the gallbladder, there is a shadow indicating precipitation. This symptom disappears after the end or temporary discontinuation of ceftriaxone therapy. Even in the presence of pain, such cases do not require surgical intervention, conservative treatment is sufficient.

In vitro studies have shown that, like other cephalosporin antibiotics, ceftriaxone is able to displace bilirubin bound to serum albumin. Therefore, in infants with hyperbilirubinemia, and especially in premature infants, the use of ceftriaxone requires even more caution. Since the drug passes into breast milk, breast-feeding should not be continued during treatment with ceftriaxone.

With prolonged use, periodic monitoring of the blood formula is necessary. Ceftriaxone is used only in a hospital setting.

Composition

One vial contains 1.0 g Ceftriaxone sodium salt.

Dosage and administration of

For adults and for children over 12 years of age: The average daily dose is 1-2 g of ceftriaxone once a day (after 24 hours). In severe cases or in cases of infections caused by moderately sensitive pathogens, the single daily dose may be increased to 4 g.

For newborns, infants and children up to 12 years of age: The following regimen is recommended for a single daily dosage:

For newborns (up to two weeks of age ): 20-50 mg / kg body weight per day (a dose of 50 mg / kg body weight is not allowed to be exceeded due to the immature enzyme system of the newborn).

For infants and children up to 12 years of age: the daily dose is 20-75 mg / kg body weight. In children weighing 50 kg or more, the dosage for adults should be followed. A dose of more than 50 mg / kg of body weight must be prescribed as an intravenous infusion for at least 30 minutes.

Duration of therapy: depends on the course of the disease.

Combination therapy:

It has been shown in experiments that there is synergism between ceftriaxone and aminoglycosides in terms of their effect on many Gram-negative bacteria. Although it is impossible to predict the potentiated effect of such combinations in advance, in cases of severe and life-threatening infections (for example, caused by Pseudomonas aeruginosa), their combined purpose is justified.

Due to the physical incompatibility of ceftriaxone and aminoglycosides, it is necessary to prescribe them in recommended doses separately!

Meningitis:

With bacterial meningitis in infants and children, the initial dose is 100 mg / kg 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 accordingly reduced. The best results were achieved with the following treatment periods:

Pathogen Duration of therapy

Neisseria meningitides 4 days

Haemophilus influenzae 6 days

Streptococcus pneumoniae 7 days

Sensitive Enterobacteriacease 10-14 days

Gonorrhea, such as

Gonorrhea, such as penicillinase strains, the recommended dose is 250 mg once intramuscularly.

Prevention in the pre- and postoperative period:

Before infected or suspected infected surgical interventions to prevent postoperative infections, depending on the risk of infection, 30-90 minutes before surgery, a single dose of ceftriaxone is recommended in a dose of 1-2 g.

Renal and hepatic insufficiency:

In patients with impaired renal function, with normal liver function, the dose of ceftriaxone is not necessary. Only with renal failure in the preterminal stage (creatinine clearance below 10 ml / min) is it necessary that the daily dose of ceftriaxone does not exceed 2 g.

In patients with impaired liver function, provided that kidney function is preserved, the dose of ceftriaxone is also not necessary.

In cases of simultaneous presence of severe pathology of the liver and kidneys, the concentration of ceftriaxone in the blood serum should be regularly monitored. In patients undergoing hemodialysis, there is no need to change the dose of the drug after this procedure.

Intramuscular injection:

For intramuscular administration, 1 g of the drug must be diluted in 3.5 ml of a 1% solution of lidocaine and injected deep into the gluteus maximus muscle, it is recommended to inject no more than 1 g of the drug in one buttock. Lidocaine solution should never be administered intravenously!

Intravenous administration:

For intravenous injection, 1 g of the drug must be diluted in 10 ml of sterile distilled water and administered intravenously slowly for 2-4 minutes.

Intravenous infusion:

Duration of an intravenous infusion is at least 30 minutes. For intravenous infusion, 2 g of the powder must be diluted in approximately 40 ml of a calcium-free solution, for example: in 0.9% sodium chloride solution, in 5% glucose solution, in 10% glucose solution, 5% levulose solution.

Side effects

Systemic side effects: from the gastrointestinal tract (about 2% of patients): diarrhea, nausea, vomiting, stomatitis and glossitis.

Changes in the blood picture (about 2% of patients) in the form of eosinophilia, leukopenia, granulocytopenia, hemolytic anemia, thrombocytopenia.

Skin reactions (about 1% of patients) in the form of exanthema, allergic dermatitis, urticaria, edema, erythema multiforme.

Other rare side effects: headaches, dizziness, increased activity of liver enzymes, congestion in the gallbladder, oliguria, increased creatinine in the blood serum, mycoses in the genital area, chills, anaphylaxis, or anaphylactic reactions. Pseudomembranous enterocolitis and blood clotting disorders are extremely rare.

Local side effects:

Phlebitis has been reported in some cases after intravenous administration. This phenomenon can be prevented by slow (within 2-4 minutes) administration of the drug. The described side effects usually disappear after discontinuation of therapy.

Overdose of

Excessively high plasma ceftriaxone concentrations cannot be reduced by hemodialysis or peritoneal dialysis. Symptomatic measures are recommended for the treatment of overdose cases.

Storage conditions

In a dark place at a temperature of no higher than 25 РC. Keep out of the reach of children.

Expiration

2 years.

Deystvuyuschee substances

Ceftriaxone

Prescription conditions from

pharmacies prescription

Dosage form

races Thief for injections and infusions

Prescribing

Adult prescribing, Children prescribing, Pregnant prescribing

Indications

From pneumonia, From infections of the biliary tract, From otitis, From sinusitis, Bronchitis, From infections of the urinary tract, From osteomyelitis, From infections infections, From infectious diseases, From cholecystitis, From respiratory tract infections

biosynthesis