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

Ceftriaxone is a third generation generic cephalosporin antibiotic for parenteral use. The bactericidal activity of the drug is due to the suppression of bacterial cell wall synthesis. Resistant to beta-lactamases (both penicillinases and cephalosporinases) produced by most gram-positive and gram-negative microorganisms. It is active against the following microorganisms:

Gram-positive aerobes: Staphylococcus aureus (methicillin-sensitive), Staphylococcus spp. (coagulase-negative), Streptococcus pyogenes (β-hemolytic, groups A), Streptococcus agalactiae (β-hemolytic, group B), Streptococcus spp. (β-hemolytic, groups of either A or B), Streptococcus pneumoniae, Streptococcus spp. groups viridans.

Note. Methicillin-resistant Staphylococcus spp. are resistant to cephalosporins, including ceftriaxone. Usually, Enterococcus faecalis, Enterococcus faecium and Listeria monocytogenes are also stable.

Gram-negative aerobes: Acinetobacter lwoffii, Acinetobacter anitratus (mainly, A. baumannii)*, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, alkaligen-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including S. amalonaticus), Citrobacter freundii**, Escherichia coli, Enterobacter aerogenes*. Enterobacter cloacae*. Enterobacter spp. (other) *, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumoniae**, Moraxella catarrhalis, Moraxella osloensis, Moraxella spp. (other), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penneri *, Proteus vulgaris *, Pseudomonas fluorescens *. Pseudomonas spp. (other), Providencia rettgeri *, Providencia spp. (other), Salmonella typhi, Salmonella spp. (non-phytophoid), Serratia marcescens *, Serratia spp. (other)*. Shigella spp .. Vibrio spp., Yersinia spp. (including Yersinia enterocolitica).

* Some isolates of these species are resistant to ceftriaxone, mainly due to the formation of β-lactamases, encoded by chromosomes.

** Some isolates of these species are stable due to the formation of a number of plasmid-mediated β-lactamases.

Note. Many strains of the above microorganisms, multidrug-resistant to other antibiotics, such as aminopenicillins and ureidopenicillins, cephalosporins I and II generations and aminoglycosides, are sensitive to ceftriaxone. Treponema pallidum sensitive to ceftriaxone in vitro and in animal experiments. Clinical isolates Pseudomonas aeruginosa resistant to ceftriaxone.

Anaerobes: Bacteroides spp. (bile-sensitive)*, Clostridium spp. (Besides Clostridium difficile), Fusobacterium spp. (at Tom number of Fusobacterium nucleatum), Gaffkya anaerobica (before called Peptococcus). Peptostreptococcus spp.

* Some isolates of these species are resistant to ceftriaxone due to the formation of β-lactamases.

Note. Many strains of β-lactamase-forming Bacteroides spp. (in particular, Bacteroides fragilis) are stable. Stable and Clostridium difficile.

Pharmacokinetics:

Suction

After intramuscular injection ceftriaxone quickly and completely absorbed into the systemic circulation. It penetrates well into the tissues and body fluids: respiratory tract, bones, joints, urinary tract, skin, subcutaneous fat and abdominal cavity organs. When inflammation of the meningeal membranes well penetrates into the cerebrospinal fluid. Bioavailability of ceftriaxone with intramuscular injection is 100%.

Distribution

With intramuscular introduction of ceftriaxone in a dose of 0.5 g and 1 g, the maximum concentration in the blood plasma is about 38 μg / ml and about 81 μg / ml, respectively, with intravenous administration at a dose of 0.5 g and 1 g - about 82 μg / ml and 168.1 ± 28.2 μg / ml, respectively. In adults, 2-24 hours after the administration of ceftriaxone at a dose of 50 mg / kg, the concentration in the cerebrospinal fluid inmany times exceeds the minimum inhibitory concentrations for the most common pathogens of meningitis. At 24 hours after intravenous administration of the drug at doses of 50-100 mg / kg body weight (newborn and infants, respectively), ceftriaxone concentrations in the cerebrospinal fluid exceed 1.4 mg / l. The maximum concentration in the cerebrospinal fluid is reached approximately 4 hours after intravenous administration and is, on average, 18 mg / l. In bacterial meningitis, the average concentration of ceftriaxone in the cerebrospinal fluid is 17% of the plasma concentration, with aseptic meningitis 4%.

The equilibrium state is established within 4 days of the drug administration. 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 plasma is less than 100 mg / ml, the binding of ceftriaxone to proteins is 95%, and at a concentration of 300 mg / ml - only 85%. Due to the lower content of albumins in the interstitial fluid, the concentration of ceftriaxone is higher in it than in plasma. The volume of distribution is 5.78-13.5 l (0.12-0.14 l / kg), in children - about 0.3 l / kg. Penetrates through the placental barrier in small quantities.

Excretion

The half-life is 6-9 hours, which allows the drug to be used once a day. The plasma clearance is 0.58-1.45 l / h, the renal clearance is 0.32-0.73 l / h. It is excreted unchanged in 33-67% of the kidneys; 40-50% is excreted with bile into the intestine, where it is biotransformed into an inactive metabolite. About 50% is output within 48 hours.

Pharmacokinetics in special clinical cases

In newborn infants, 70% of the drug is excreted by the kidneys. In newborns (up to 8 days) and in elderly people (over 75 years), the elimination half-life increases significantly.

In renal failure or liver disease in adults pharmacokinetics ceftriaxone hardly changes, half-life period is lengthened slightly. If only the kidney function is disrupted, the excretion with bile increases, if only the pathology of the liver occurs, then the excretion of ceftriaxone by the kidneys increases. In patients on hemodialysis, with a clearance of creatinine (CC) 0-5 ml / min, the elimination half-life is 14.7 hours; with SC 5-15 ml / min - 15.7 hours; with SC 16-30 ml / min - 11.4 hours; with a CK of 31-60 ml / min - 12.4 hours.

In children with meningitis, the half-life after intravenous administration at a dose of 50-75 mg / kg is 4.3-4.6 hours.

Ceftriaxone is not excreted by hemodialysis.

Indications:Infectious-inflammatory diseases caused by microorganisms sensitive to ceftriaxone: infections of the abdominal cavity (including peritonitis), inflammatory diseases of the gastrointestinal tract, bile ducts (including cholangitis, empyema of the gallbladder), infections of bones and joints, infections of the skin and soft tissues (including infected wounds and burns), infections of the genitourinary system (including pyelitis, acute and chronic pyelonephritis, cystitis, prostatitis, epididymitis), infections of the upper and lower respiratory tract LOP-organs (including pneumonia, acute and chronic bronchitis, lung abscess, pleural empyema), uncomplicated gonorrhea, bacterial septicemia, bacterial meningitis and endocarditis, chancroid and syphilis, Lyme disease (tick-borne borreliosis), infections in immunocompromised patients . Prevention of postoperative complications.

Contraindications:Hypersensitivity to ceftriaxone and other cephalosporins, penicillins, carbapenems. Hyperbilirubinemia or jaundice in term infants. Premature newborns,not reached the "prospective" age of 41 weeks (taking into account the period of intrauterine development and age). Newborn babies who are shown intravenous administration of calcium-containing solutions. Acidosis, hypoalbuminemia in full-term newborns. The first trimester of pregnancy. Lactation period.

Carefully:

Renal and / or hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs, II-III trimester of pregnancy.

Pregnancy and lactation:

The use of the drug in the II and III trimester of pregnancy is possible only in those cases when the intended use for the mother exceeds the potential risk to the fetus.

If you need to use the drug during lactation, you should stop breastfeeding.

Dosing and Administration:

The drug is used intramuscularly and intravenously (either jet or drip).

For adults and children over 12 years of age: the usual dose is 1-2 g once a day or divided into two injections (every 12 hours). In severe cases or infections, the causative agents of which have only moderate sensitivity to ceftriaxone, the daily dose may be increased to 4 g.

For newborns (up to 14 days): prescribe 20-50 mg / kg once a day.The maximum daily dose is 50 mg / kg.

For infants and young children (from 15 days to 12 years): prescribe 20-80 mg / kg once a day.

Children with a body weight of 50 kg and above, doses intended for adults are prescribed.

Doses of 50 mg / kg or more for intravenous administration should be given as an intravenous infusion for at least 30 minutes.

In the treatment acute otitis media In children, a single intramuscular injection of 50 mg / kg is recommended (but not more than 1 g).

With bacterial meningitis in infants and young children, the dose is 100 mg / kg once a day. The maximum daily dose is 4 g.

The duration of therapy depends on the type of pathogen and can range from 4 days with meningitis caused by Neisseria meningitidis, up to 10-14 days with meningitis caused by sensitive strains Enterobacteriaceae. After identifying the pathogen and determining its sensitivity, the dose can be reduced accordingly.

With Lyme disease adults and children over 12 years of age are prescribed 50 mg / kg once a day. The maximum daily dose is 2 g. The duration of treatment is 14 days.

With uncomplicated gonorrhea (caused by penicillinase-forming and penicillinase-forming strains), a single intramuscular injection of 250 mgpreparation.

To patients of advanced age appoint usual doses intended for adults, without adjusting for age.

With the aim of prevention of postoperative infections depending on the degree of infectious risk, 1-2 g once for 30-90 minutes before the operation is introduced. In operations on the colon and rectum, simultaneous (but separate) administration of ceftriaxone and one of the preparations of the 5-nitroimidazoles group is effective.

In patients with impaired renal function there is no need to correct the dose of ceftriaxone provided normal liver function. The daily dose of the drug should not exceed 2 g only in cases of chronic renal failure with a creatinine clearance less than 10 ml / min.

In patients with impaired hepatic function There is no need to correct the dose of ceftriaxone provided that the normal function of the kidneys is maintained.

In patients with renal and hepatic impairment the daily dose should not exceed 2 g without determining the concentration of ceftriaxone in the blood plasma.

Patients on hemodialysis, no additional administration of the drug after the hemodialysis session is required.The rate of excretion of ceftriaxone in such patients may be reduced, so the concentration of ceftriaxone in the blood plasma should be monitored in order to timely dose correction.

Treatment with ceftriaxone should continue for 2-3 days after the disappearance of symptoms and signs of infection. The duration of treatment is usually 4-14 days; with complicated infections, longer treatment may be required. The course of treatment for infections caused by Streptococcus pyogenes, must be at least 10 days.

Rules for the preparation of injectable solutions

Use only freshly prepared solutions.

For intramuscular injection 0.5 g of the drug is dissolved in 2 ml of water for injection, 1 g in 3.5 ml of water for injection. To reduce pain with intramuscular injections, it is permissible to administer the drug with 1% lidocaine solution. Enter deep into the gluteus muscle or thigh muscle. It is recommended to inject no more than 1 g of the drug into one muscle. A solution of lidocaine can never be administered intravenously!

For intravenous administration 0.5 g of the drug is dissolved in 5 ml of water for injection, 1 g in 10 ml of water for injection.The solution is administered slowly for 2-4 minutes.

For intravenous infusion 2 g of the drug is dissolved in 40 ml of water for injection or one of the solutions that do not contain calcium (0.9% sodium chloride solution, 0.45% sodium chloride solution + 2.5% dextrose solution, 5% dextrose solution; 10% dextrose solution, 6% dextran solution in 5% dextrose solution, 6-10% solution of hydroxyethyl starch). The solution is introduced for 30 minutes.

Side effects:

Allergic reactions: rash, itching, chills or fever, allergic dermatitis, urticaria, edema, erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome, allergic pneumonitis, anaphylaxis, bronchospasm, serum sickness, anaphylactoid reactions.

From the nervous system: headache, dizziness, convulsions, vertigo.

From the digestive system: nausea, vomiting, diarrhea or constipation, impaired taste, flatulence, pseudomembranous colitis, abdominal pain, cholelithiasis, colitis, dyspepsia, bloating, bile stasis ("sluggish phenomenon"), jaundice, stomatitis, glossitis.

From the hematopoiesis: anemia (including hemolytic), eosinophilia, thrombocytosis,leukopenia, neutropenia, lymphopenia, thrombocytopenia, agranulocytosis, basophilia, leukocytosis, lymphocytosis, monocytosis, granulocytopenia.

From the genitourinary system: candidiasis of the vagina, vaginitis, oliguria, glucosuria, hematuria, nephrolithiasis.

Local reactions: with intravenous injection - phlebitis, soreness, tightening along the veins; intramuscular injection - soreness, sensation of warmth, tightness or condensation at the injection site.

Laboratory indicators: increase (decrease) in prothrombin time, increase in thromboplastin time, increase in activity of "hepatic" transaminases and alkaline phosphatase, hyperbilirubinemia, hypercreatininemia, increased urea concentration, presence of sediment in urine.

Other: increased sweating, "tides" of blood to the face, epistaxis, palpitations, superinfection, pancreatitis, the formation of precipitates in the lungs.

Overdose:

Symptoms: increased severity of side effects of the drug.

Treatment: symptomatic therapy. There is no specific antidote.

Hemodialysis and peritoneal dialysis are not effective.

Interaction:

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

Ceftriaxone and aminoglycosides have a synergistic effect on many Gram-negative bacteria (incl. Pseudomonas aeruginosa).

Antagonism with chloramphenicol in vitro.

Ceftriaxone, suppressing the intestinal microflora, interferes with the synthesis of vitamin K. With simultaneous administration with drugs that reduce platelet aggregation (non-steroidal anti-inflammatory drugs, salicylates, sulfinpyrazone), the risk of bleeding increases.

With a simultaneous appointment with anticoagulants, there is an increased anticoagulant effect.

Ceftriaxone reduces the effectiveness of oral contraceptives, therefore it is recommended to use additional non-hormonal contraceptives.

With the simultaneous use of large doses of the drug and "loop" diuretics (eg, furosemide), renal dysfunction was not observed.

Indications that ceftriaxone increases the nephrotoxicity of aminoglycosides

Does not interact with probenecid.

Pharmaceutical interaction

Ceftriaxone should not be mixed or administered concurrently with solutions containing calcium ions.

The formation of precipitates of calcium salts of ceftriaxone can also occur when the preparation and calcium-containing solutions are mixed using one venous access.

Do not use the drug simultaneously with calcium-containing solutions for intravenous administration, including long-term infusions of calcium-containing solutions, for example, with parenteral nutrition using Yconnector.

For all groups of patients, except for newborns, it is possible to consistently administer the preparation and calcium-containing solutions with thorough washing of the infusion systems between infusions of a compatible liquid.

Pharmaceutically incompatible with solutions containing other antibiotics, incl. with amsacrine, vancomycin, fluconazole and aminoglycosides.

Special instructions:

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.

Ceftriaxone does not contain Nmethylthiothetrazole group, therefore, when interacting with ethanol, it does not lead to the development of disulfiram-like reactions and bleeding that are inherent in some cephalosporins.

In rare cases, with ultrasound of the gallbladder, blackouts (precipitates of the calcium salt of ceftriaxone) are observed, which disappear after the drug is discontinued. With the development of symptoms or signs indicating a possible gallbladder disease or if there are ultrasound signs of a "sluggish phenomenon," it is recommended that the drug be discontinued.

When using the drug, rare cases of pancreatitis, which developed, possibly, as a result of obstruction of the biliary tract, are described. Most patients had risk factors for congestion in the biliary tract (previous drug therapy, severe co-morbidities, completely parenteral nutrition); However, the starting role of precipitate formation in the biliary tract under the influence of ceftriaxone can not be ruled out.

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

As with the use of other cephalosporins. at treatment by a preparation development of an autoimmune hemolytic anemia is possible.Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported. In case of anemia, therapy with the drug should be discontinued.

When using the drug, cases of diarrhea caused by Clostridium difficile (pseudomembranous colitis), varying degrees of severity: from mild to colitis with fatal outcome. Careful collection of anamnesis is necessary, since cases of diarrhea caused by Clostridium difficile, more than 2 months after antibiotic therapy. In accordance with clinical indications, appropriate treatment should be prescribed (compensation for loss of fluid, electrolytes, protein, antibiotic therapy for Clostridium difficile, surgery). When the development of pseudomembranous colitis is contraindicated the appointment of drugs that inhibit the intestinal motility.

As with other antibacterial drugs, superinfection may develop.

In combination with severe renal and hepatic insufficiency, as well as in patients on hemodialysis, the concentration of ceftriaxone in the blood plasma should be regularly determined.

Cases of fatal reactions as a result of deposits of ceftriaxone-calcium precipitates 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 for parenteral nutrition), and also administered simultaneously, incl. through separate accesses for infusions at different sites. Theoretically, based on the calculation of 5 T1 / 2 ceftriaxone interval between the administration of ceftriaxone and calcium-containing solutions should be at least 48 hours.

Data on the possible interaction of ceftriaxone with oral calcium-containing drugs, as well as ceftriaxone for intramuscular injection with calcium-containing drugs are absent.

In the treatment of ceftriaxone, false positive results of Coombs test, a test for galactosemia, may be noted. False positive results can be obtained in the determination of glucose in urine by non-enzyme methods, therefore, during therapy with the drug ceftriaxone Glucosuria, if necessary, should be determined only by the enzyme method.

When allergic reactions occur, the drug should be discarded. Serious reactions of hypersensitivity may require immediate therapy: intravenous epinephrine and other forms of maintenance treatment.

Research in vitro showed that, like other cephalosporin antibiotics, ceftriaxone is able to displace bilirubin, associated with serum albumin.

Effect on the ability to drive transp. cf. and fur:

Given the possible development of side effects, during the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities requiring increased concentration and speed of psychomotor reactions.

Form release / dosage:

Powder for the preparation of solution for intravenous and intramuscular injection 0.5 g or 1.0 g.

Packaging:

For 0.5 g and 1.0 g of active substance in 10 ml vials hermetically sealed with rubber stoppers and crimped aluminum or combined caps.

1 bottle with instruction for use is placed in an individual pack of cardboard.

For hospitals: 50 bottles with an equal number of instructions for medical use are placed in a box of cardboard.

Complete form of release: 1 vial of the preparation (0.5 g of active substance) complete with 1 ampoule of the solvent "Water for Injection" of 5 ml or 1 bottle of the drug (1.0 g of active substance) complete with 2 ampoules of the solvent "Water for Injection" 5 ml each with instructions for medical use and a scarifier or a knife ampoule into a pack of cardboard. When packing ampoules with a ring or break point, the scarifier or ampoule knife is not inserted.

Storage conditions:In a dry, the dark 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.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002294

Date of registration:17.08.2007

The owner of the registration certificate:Company DEKO, LLC Company DEKO, LLC Russia

Manufacturer: & nbsp

Company DEKO, LLC Russia

Information update date: & nbsp25.11.2015

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)