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

Cephalosporin antibiotic III Generation of a broad spectrum of action for parenteral administration. Bactericidal activity is due to the suppression of bacterial cell wall synthesis. It is characterized by resistance to the action of most beta-lactamases of Gram-positive and Gram-negative microorganisms

It is active against the following microorganisms:

gram-positive aerobes: Staphylococcus aureus (including strains producing penicillinase), Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus spp. groups viridans;

gram-negative aerobes: Acinetobacter lwoffii, Acinetobacter anitratus (mainly, A. baumannii); Borrelia burgdorferi, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae (including strains that form penicillinase), Haemophilus parainfluenzae, Klebsiella spp. (incl. Klebsiella pneumoniae), Moraxella catarrhalis (including penicillinase-producing strains), Morganella morganii, Neisseria gonorrhoeae (including strains that form penicillinase), Neisseria meningitidis, Proteus mirabilis, Proteus vulgaris, Serratia spp. (incl. Serratia marcescens); individual strains Pseudomonas aeruginosa are also sensitive;

anaerobes: Bacteroides spp. (bile-sensitive), Clostridium spp. (Besides Clostridium difficile), Peptostreptococcus spp.

Has activity in vitro for most strains of the following microorganisms, although the clinical significance of this is unknown: Citrobacter diversus, Citrobacter freundii, Providencia spp. (in t.h. Providencia rettgeri), Salmonella spp., including Salmonella typhi, Shigella spp., Streptococcus agalactiae, Bacteroides bivius, Bacteroides melaninogenicus. Staphylococcus spp., resistant to methicillin, resistant to cephalosporins. Resistant to ceftriaxone, many strains of streptococcus group D and enterococci, in t.h. Enterococcus faecalis; many strains of β-lactamase-forming Bacteroides spp. (in particular Bacteroides fragilis).

Pharmacokinetics:

Bioavailability is 100%, the time to reach the maximum concentration (TCmax) after intramuscular (IM) administration is 2-3 hours, after intravenous (IV) administration - at the end of the infusion. The maximum concentration (Cmax) after i / m administration in doses of 0.5 g and 1 g is 38 and 76 μg / ml, respectively. Cmax with iv introduction in doses of 0.5 g, 1 g and 2 g - 82, 151 and 257 μg / ml, respectively. In adults, 2-24 hours afterThe administration in a dose of 50 mg / kg concentration in the cerebrospinal fluid (CSF) many times exceeds the minimum inhibitory concentration for the most common pathogens of meningitis. It penetrates well into CSF with inflammation of the meninges. The connection with plasma proteins is 83-96%. The volume of distribution is 0,12-0,14 l / kg (5,78-13,5 l), in children -0,3 l / kg, the plasma clearance is 0,58-1,45 l / h, the renal - 0.32-0.73 l / h. The half-life period (T1 / 2) after IM was 5.8-8.7 hours after IV injection 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 hours, with SC 15-15 ml / min 15.7 hours, 16-30 ml / min 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:

Infectious and inflammatory diseases caused by microorganisms sensitive to ceftriaxone: abdominal organs (peritonitis, inflammatory diseases of the gastrointestinal tract, bile ducts, including cholangitis, empyema of the gallbladder), pelvic organs, lower respiratory tract (v. h. pneumonia, abscess of the lung, empyema of the pleura), bones and joints, skin and soft tissues (incl.infected wounds and burns), kidney and urinary tract (complicated and uncomplicated), ENT organs, genital organs, bacterial meningitis, bacterial septicemia, Lyme disease. Prevention of postoperative infections. Infectious diseases in persons with weakened immunity.

Contraindications:

Hypersensitivity to ceftriaxone, other cephalosporins, penicillins, other beta-lactam antibiotics. Hyperbilirubinemia or jaundice in term infants. Premature newborns under the "expected" age of 41 weeks (including the term of intrauterine development and age). Newborn babies who are shown intravenous administration of calcium-containing solutions. Acidosis, hypoalbuminemia in full-term newborns.

Carefully:Renal and / or hepatic insufficiency, ulcerative colitis, enteritis or colitis associated with the use of antibacterial drugs.

Pregnancy and lactation:The use of ceftriaxone in pregnancy is permissible if the expected benefit to the mother exceeds the potential risk to the fetus.If you need to use the drug during lactation at the time of treatment should stop breastfeeding.

Dosing and Administration:

Intravenously (intravenously), infusion. Do not use calcium-containing solutions to dilute the preparation! If necessary, single administration at a dose of more than 1 g, as well as for the treatment of severe infections by intravenous administration is preferred. When administered intravenously at a dose of 50 mg / kg and above, intravenous infusion should be used for at least 30 minutes.

Adults and children over 12 years of age. The initial daily dose, depending on the type and severity of the infection, is 1-2 g once a 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) once a day for 14 days.

For the prevention of postoperative 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-nitroimidazole group is recommended.

Newborns, infants and children under 12 years of age. When using the drug once a day, it is recommended to adhere to the following dosing regimens:

Newborns (up to 14 days) - 20-50 mg / kg of body weight once a day.The daily dose should not exceed 50 mg / kg of body weight.

Newborns, infants and young children (from 15 days to 12 years): 20-80 mg / kg body weight once a day. The total daily dose in children should not exceed 2 g. Children weighing 50 kg or more receive doses for adults.

Bacterial meningitis. In bacterial meningitis in infants and young children, treatment starts with a dose of 100 mg / kg (but not more than 4 g) once a day. After identifying the pathogen and determining its sensitivity, the dose can be reduced accordingly. The best results in the treatment of meningitis caused by Neisseria meningitidis, were achieved with a treatment duration of 4 days; with meningitis caused by Haemophilus influenzae - 6 days; Streptococcus pneumoniae - 7 days.

In chronic renal failure (CC 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, it is necessary to control the concentration of ceftriaxone in the plasma, since its excretion in such patients may be slowed down (dose correction may be required).

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.

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.

Preparation and introduction of solutions.

Use only freshly prepared solutions.

Intravenous infusion: 2 g of the drug dissolve in 40 ml of a solution that does not contain calcium ions (sodium chloride solution 0.9%, dextrose solution 5% or 10%), the infusion should last at least 30 minutes.

Side effects:

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

Local reactions: with iv introduction - phlebitis, tenderness, compaction along the vein.

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

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

From the urinary system: oliguria, glucosuria, hematuria, nephrolithiasis.

From the digestive system: diarrhea, nausea, vomiting, taste disorder, pseudomembranous colitis, pancreatitis, colitis, dyspepsia, bloating, "sluggish phenomenon" of the gallbladder, abdominal pain, jaundice, cholelithiasis.

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

From the respiratory system: bronchospasm, the formation of precipitates in the lungs.

From the side of the cardiovascular system: a feeling of the heartbeat.

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

Other: increased sweating, "hot flushes" of blood, epistaxis, stomatitis, glossitis.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:Symptoms: nausea, vomiting, diarrhea, confusion, convulsions. Treatment: symptomatic. Hemodialysis and peritoneal dialysis are not effective.

Interaction:

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, no.

It does not contain N-metiltiotetrazolnoy group, therefore the interaction with ethanol did not lead to the development disulfiramopodobnyh reactions inherent in some cephalosporins. Probenicid does not affect the excretion of ceftriaxone. Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone. Antagonism with chloramphenicol in vitro.

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

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 with long infusions of calcium-containing solutions, for example, with parenteral nutrition using the Y-connector. 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.

Ceftriaxone reduces the effectiveness of oral contraceptives, therefore it is recommended to use additional non-hormonal contraceptives. If you are taking other drugs, consult a doctor.

Special instructions:

Ceftriaxone is used only in a hospital. When concomitant severe renal and hepatic failure, as well as in patients on hemodialysis, should be regularly to determine the concentration of drug in plasma.

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 (precipitates of the calcium salt of ceftriaxone) are observed, which disappear after the cessation of treatment.With the development of the symptoms or signs indicating the possible gallbladder disease, or in the presence of ultrasound signs "sludge phenomenon" is recommended to stop administering the drug.

When the drug is used, rare cases of pancreatitis that develop, possibly, as a result of biliary tract obstruction are described. Most patients had risk factors for congestion of 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.

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

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.There are cases of fatal reactions as a result of deposition of precipitates the calcium salt of ceftriaxone in the lungs and kidneys of neonates. 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 not be mixed with calcium-containing solutions (including those for parenteral nutrition) and administered simultaneously, including through separate accesses for infusions at different sites. Theoretically, based on the calculation 5 T1 / 2 ceftriaxone interval between administration of ceftriaxone and calcium solutions should be at least 48 hours. The data on possible interaction of ceftriaxone with oral calcium-containing agents, and ceftriaxone for the / m of a calcium-containing preparations (in / and oral ) are absent.

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

Despite the detailed collection of anamnesis, one can not exclude the possibility of developing an anaphylactic shock,which requires immediate therapy - first in / in injected epinephrine, then glucocorticosteroids.

Effect on the ability to drive transp. cf. and fur:Care should be taken when driving a car and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Powder for solution for infusion 2.0 g.

Packaging:

Powder for the preparation of a solution for infusions 2.0 g of active substance in glass bottles with a capacity of 10 ml, 20 ml.

1 bottle with instructions for use in a pack of cardboard.

10 bottles with instructions for use in a cardboard box.

For hospitals:

- 50 bottles with an equal number of instructions for use in a cardboard box;

- from 1 to 50 bottles with an equal number of instructions for use in a cardboard box.

Storage conditions:In 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:LP-002661

Date of registration:16.10.2014

Date of cancellation:2019-10-16

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp14.11.2015

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)