Ceftriaxone - instructions for use, dose, side effects, contraindications

Ceftriaxone is a third generation cephalosporin antibiotic for parenteral use, has a bactericidal effect, inhibits the synthesis of the cell membrane, in vitro suppresses the growth of most gram-positive and gram-negative microorganisms. Ceftriaxone is resistant to beta-lactamase enzymes (both penicillinase and cephalosporinase, produced by the majority

gram-positive and gram-negative bacteria). Effective against the following microorganisms:

Gram-positive

Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus A (Str.pyogenes), Streptococcus Have (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) also resistant to ceftriaxone.

Literature

Aeromonas spp., Alcaligenes spp., Branhamella catarrhalis, Citrobacter spp., Enterobacter spp. (some strains are stable), Escherichia coli, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella spp. (at Tom number of Kl. pneumoniae), Moraxella spp., Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa (some strains are stable), Salmonella spp. (at Tom number of S. typhi), Serratia spp. (at Tom number of S. marcescens), Shigella spp., Vibrio spp. (at Tom number of V. cholerae), Yersinia spp. (at Tom number of 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, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone as in vitro, and in experiments on animals. 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. (at Tom number of CI. difficile), Fusobacterium spp. (Besides F. mostiferum. F. varium), Peptococcus spp., Peptostreptococcus spp.

Note: some strains of many Bacteroides spp. (for example, in. fragilis), producing beta-lactamase, are resistant to ceftriaxone. To determine the sensitivity of microorganisms, discs containing ceftriaxone, since it is shown that in vitro to classical cephalosporins, certain strains of pathogens can be stable.

Pharmacokinetics:

Bioavailability of ceftriaxone with intramuscular injection (in / m) is 100%. With intravenous administration (IV) ceftriaxone quickly diffuses into the interstitial fluid, where its bactericidal action against pathogens sensitive to it persists for 24 hours.

The time to reach the maximum concentration (C max) after IM is 2-3 hours, after IV introduction at the end of the infusion. The maximum concentration after IM in doses of 0.5 and 1 g is 38 and 76 μg / ml, respectively. Cmax with iv introduction in doses of 0.5 and 1 and 2 g -82.151 and 257 μg / ml, respectively.

In adults, 2-24 hours after administration at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid is many times greater than the minimal inhibitory concentration for the most common meningitis pathogens. Well penetrates into the cerebrospinal fluid with inflammation of the meninges.Connection with blood plasma proteins - 83-96%. The volume of distribution - 0,12-0,14 l / kg (5,78-13,5 l), in children - 0,3 l / kg, plasma clearance - 0,58-1,45 l / h, renal - 0.32-0.73 l / h.

The half-life (T1 / 2) after IM for 5-8-8.7 hours, after IV introduction at a dose of 50-75 mg / kg in children with meningitis - 4.3-4.6 hours; in patients on hemodialysis (creatinine clearance 0-5 ml / min), 14.7, with KK - 5-15 ml / min - 15.7 h, 16-30 - 11.4 h, 31 -60 ml / min-12.4 h.

It is excreted unchanged - 33-67% by the kidneys; 40-50% - with bile in the intestine, where the inactivation occurs. In newborn infants, about 70% of the drug is excreted by the kidneys. Hemodialysis is ineffective.

Indications:

Infections caused by ceftriaxon-sensitive pathogens:

bacterial meningitis, infections of the abdominal cavity (peritonitis, inflammatory diseases of the gastrointestinal tract, bile ducts, tons of cholangitis, empyema of the gallbladder), infections of the pelvic organs, infections of bones and joints, skin and soft tissues (including those infected wounds and burns), infections in patients with a decreased function of the immune system, urinary tract infections (complicated and uncomplicated), infections of the lower respiratory tract (including pneumonia, lung abscess, pleural empyema), as well as acute bacterial middle it,uncomplicated gonorrhea (cervical / urethral and rectal), bacterial septicemia.

Prevention of infection in the postoperative period.

Infectious diseases in patients with weakened immunity.

Contraindications:Hypersensitivity (including other cephalosporins, penicillins and carbapenems), hyperbilirubinemia in newborns, use in newborns, which are shown in / in the introduction of solutions containing calcium.

Carefully:Use in premature infants, renal and / or hepatic insufficiency,) ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs.

Pregnancy and lactation:

There are no data on the use of ceftriaxone in pregnant women. The application is possible only in cases where the potential benefit to the mother exceeds the potential risk to the fetus.

Ceftriaxone is excreted in breast milk in low concentrations. Use in nursing women is recommended with caution, it is necessary to abolish breastfeeding.

Dosing and Administration:

The drug is used intramuscularly and intravenously. Do not use calcium-containing solutions to dilute the preparation!

In adults initial daily dose depending on the type and severity of the infection is 1-2 g 1 time per day or divided into 2 doses (every 12 hours), the total daily dose should not exceed 4 g.

Lyme disease: adults and children - 50 mg / kg (but not more than 2 g) 1 time per knock for 14 days.

With uncomplicated gonorrhea - 250 mg / kg IM once.

For prophylaxis after surgical complications - once 1 g for 30-60 minutes before the operation. In operations on the colon and rectum, additional administration of a drug from the 5-nitroamidazole group is recommended.

Dose for newborns - 20-50 mg / kg / day.

For the treatment of skin and soft tissue infections recommended daily intake in children - 50-75 mg / kg, divided into 2 doses (every 12 hours). The total daily intake for children should not exceed 2 g.

With bacterial meningitis in children the initial dose is 100 mg / kg (but not more than 4 g) once a day, then 100 mg / kg / day (but not more than 4 g) once a day or divided into 2 divided doses (every 12 hours). The duration of treatment is 7-14 days.

In the treatment of acute otitis media in children it is recommended to take a single IV IM administration at a dose of 50 mg / kg (but not more than 1 g).

When treating other infections in children the recommended daily intake in children is 50-75 mg / kg, divided into 2 doses (every 12 hours).The total daily intake in children should not exceed 2 g.

In children with a body weight of 50 kg and above, doses for adults are used. A dose of more than 50 mg / kg of body weight should be given as an IV infusion for 30 minutes.

In chronic renal failure (creatine clearance less than 10 ml / min) - the daily dose should not exceed 2 g; patients on hemodialysis do not require an additional dose after a hemodialysis session, however, the concentration of ceftriaxone in the blood plasma should be monitored, since its excretion in such patients may be slowed down (dose adjustment may be required).

Treatment with ceftriaxone should continue for at least 2 more days. after the disappearance of symptoms and signs of infection. The course of treatment is usually 4-14 days; with complicated infections, a longer duration of administration may be required. The course of treatment for infections caused by Streptococcus pyogenes, must be at least 10 days.

Children with skin and soft tissue infections - in a daily dose of 50-75 mg / kg once a day or 25-37.5 mg / kg every 12 hours, not more than 2 g / day. In severe infections of other sites, 25-37.5 mg / kg every 12 hours, but not more than 2 g / day.

With average otitis - IM once a day 50 mg / kg not more than 1 g.

Patients with chronic renal insufficiency correction of the dose is required only with QC less than 10 ml / min. In this case, the daily dose should not exceed 2 g.

In patients with renal-hepatic insufficiency, the daily dose should not exceed 2 g without determining the concentration of the drug in the blood plasma.

Right-hander of preparation and introduction of solutions: only freshly prepared solutions should be used.

For intramuscular injection 1 g of the drug is dissolved in 3.5 ml of a 1% solution of lidocaine. It is recommended to enter no more than 1 g in one buttock.

For intravenous administration 1 g of the drug is dissolved in 10 ml of water for injection.

Enter into / in slowly (2-4 minutes).

For intravenous infusion dissolve 2 g in 40 ml of a solution that does not contain calcium (0.9% sodium chloride solution, 5-10% dextrose (glucose) solution, 5% levulose solution).

Doses of 50 mg / kg or more should be administered intravenously in drip, for 30 minutes.

Side effects:

Allergic reactions: urticaria, chills or fever, skin rash, itching, bronchospasm, eosinophilia, erythema, polymorphic exudative (including Stevens-Johnson syndrome), serum sickness, angioedema, anaphylactic shock.

From the digestive system: nausea, vomiting, diarrhea or constipation, flatulence, abdominal pain, taste disturbance, stomatitis, glossitis, enterocolitis, pseudomembranous, liver dysfunction (increased activity "liver" enzymes, at least - alkaline phosphatase, or bilirubin, cholestatic icterus), gallbladder psevdoholelitiaz ("sluge" - a syndrome), a dysbacteriosis.

From the hematopoiesis: leukopenia, neutropenia, granulocytopenia, lymphopenia, thrombocytosis, thrombocytopenia, hemolytic anemia, hypocoagulation, decrease in plasma clotting factor concentration (II, VII, IX, X), prolongation of prothrombin time.

From the urinary system: renal dysfunction, azotemia,

increase in the concentration of urea in the blood, hypercreatininaemia, glucosuria, cylindruria, hematuria), oliguria, anuria.

From the genitourinary system: candidiasis of the vagina, vaginitis.

Local reactions: phlebitis, consolidation along the vein, soreness and infiltration at the site of the / m administration.

Other: headache, dizziness, nosebleeds, candidiasis, increased sweating, "hot flashes" of blood.

Undesirable reactions with a frequency of less than 0.1%: abdominal pain, agranulocytosis, allergic pneumonitis, anaphylaxis, basophilia, cholelithiasis, bronchospasm, colitis, dyspepsia, epistaxis, bloating, "sludge phenomenon" of the gallbladder, glucosuria, hematuria, jaundice, leukocytosis, lymphocytosis, monocytosis, nephrolithiasis, palpitations, convulsions, serum sickness.

Overdose:Excessively high concentrations of ceftriaxone in the blood plasma can not be reduced by hemodialysis or peritoneal dialysis. Symptomatic measures are recommended for the treatment of overdose cases.

Interaction:

Ceftriaxone and aminoglycosides have a synergistic effect on many Gram-negative bacteria.

Nonsteroidal anti-inflammatory drugs and other inhibitors of platelet aggregation increase the likelihood of bleeding.

It does not contain N-metiltiotetrazolnoy group, therefore the interaction with ethanol did not lead to the development disulfiramopodobnyh reactions inherent in some cephalosporins.

With simultaneous use with "loop" diuretics and other nephrotoxic drugs, the risk of nephrotoxic effect increases.

Pharmaceutically incompatible with solutions containing calcium (including Hartman and Ringer's dissolution), as well as with amsacrine, vancomycin, fluconazole and aminoglycosides.

Antagonism with chloramphenicol in vitro.

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

Special instructions:

Applied only in a hospital!

With simultaneous severe renal and hepatic insufficiency, the concentration of the drug in the blood plasma should be regularly determined.

In patients who are on hemodialysis, it is necessary to monitor the concentration of ceftriaxone in the blood 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 of the gallbladder, blackouts are observed that disappear after cancellation (even if this phenomenon is accompanied by pain in the right hypochondrium, it is recommended to continue the prescription of the antibiotic and conduct symptomatic treatment).

Ceftriaxone does not contain N-methylthiothetrazole group, which causes disulfiram-like effects with simultaneous use of ethanol and bleeding that are inherent in some cephalosporins.

Despite the detailed collection of anamnesis, which is the rule for other cephalosporin antibiotics, one can not exclude the possibility of developing an anaphylactic shock that requires immediate therapy - first intravenously, inject epinephrine (adrenaline), then, glucocorticoids.

Research in vitro showed that, like other cephalosporin antibiotics, ceftriaxone is able to displace bilirubin, associated with serum albumin. Therefore, in newborns with hyperbilirubinemia and, especially, in preterm neonates, the use of ceftriaxone requires even greater caution.

Freshly prepared Ceftriaxone solutions are physically and chemically stable for 6 hours at room temperature.

When using the drug, rare cases of prothrombin time change are described. Patients with a vitamin K deficiency (a synthesis disorder, an eating disorder) may need to monitor prothrombin time and prescribe vitamin K (10 mg / week) with an increase in prothrombin time before or during therapy.

Cases of fatal reactions as a result of deposition of ceftriaxone-calcium presitites in the lungs and kidneys of newborns are described.Theoretically there is a probability of interaction of ceftriaxone with calcium-containing solutions for intravenous administration and in other age groups of patients, therefore ceftriaxone should not be mixed with calcium-containing solutions (including parenteral nutrition), and also administered simultaneously, including through separate access for infusion in various areas. Theoretically, based on the calculation of 5 T1 / 2 ceftriaxone, the interval between the administration of ceftriaxone and calcium-containing solutions should be at least 48 hours. Data on the possible interaction of ceftriaxone with calcium-containing drugs for ingestion (intravenously and intravenously) are absent.

In the treatment with ceftriaxone, false positive results of Coombs test, a test for galactosemia, glucose in urine (glucosuria is recommended to be determined only by enzyme method).

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection in vials of 1.0 g.

Packaging:

A bottle with a preparation together with the instruction for use is placed in a pack of cardboard.

10 bottles of the drug, along with instructions for use, are placed in a cardboard pack.

50 bottles together with instructions for use are placed in a box of cardboard (for hospitals).

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-001871

Date of registration:26.09.2011

The owner of the registration certificate: Mapichem AG Mapichem AG Switzerland

Manufacturer: & nbsp

CSPS ZHONGNUO PHARMACEUTICAL (SHIJIAZHUANG), Co., Ltd. China

Representation: & nbspMapichem AGMapichem AG

Information update date: & nbsp17.11.2015

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)