Ceftriaxone solution 1g vials, 1pc

Composition

Each bottle contains: Active ingredient:  ceftriaxone sodium trisesquihydrate – 2.386 g (in terms of ceftriaxone-2.0 g).

Pharmacological action

Pharmacotherapeutic group:

antibiotic-cephalosporin

ATX code:

J01DD04

Pharmacological properties

Pharmacodynamics . Ceftriaxone is a parenteral cephalosporin antibiotic of the third generation. The bactericidal activity of ceftriaxone is due to the suppression of cell wall synthesis. In vitro, ceftriaxone has a broad spectrum against gram-negative and gram-positive microorganisms. It is highly resistant to most beta-lactamases (both penicillinases and cephalosporinases) produced by gram-positive and gram-negative bacteria.

Ceftriaxone is usually active against the following microorganisms: Gram-positive aerobesstaphylococcus aureus (methicillin-sensitive), coagulase-negative staphylococci, Streptococcus pyogenes (β-hemolytic, Group A), Streptococcus agalactiae (p-hemolytic, Group B), p-hemolytic streptococci (groups neither A nor B), Streptococcus viridans, Streptococcus pneumoniae. Note. Methicillin-resistant Staphylococcus spp. they are resistant to cephalosporins, including ceftriaxone. Generally, Enterococcus faecalis, Enterococcus faecium, and Listeria monocytogenes are also resistant.

Gram-negative Aerobesacinetobacter lwoffii, Acinetobacter anitratus (mainly A. baumanni)*, Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, alkaligene-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including C. amalonaticus), Citrobacter freundii*, Escherichia coli, Enterobacter aerogenes*, Enterobacter cloacae*, Enterobacter spp. (other)*, Haemophilus ducreyi, Haemophilus influenzae, Haemophilus parainfluenzae, Hafnia alvei, Klebsiella oxytoca, Klebsiella pneumonia**, Moraxella catarrhalis (previously called Branhamella catarrhalis), Moraxella osloensis, Moraxella spp. (others), 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-typhoid), Serratia marcescens*, Serratia spp. (other)*, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (others).

*Some isolates of these species are resistant to ceftriaxone, mainly due to the formation of p-lactamases encoded by chromosomes. **Some isolates of these species are resistant due to the formation of a number of plasmid-mediated p-lactamases.

Note. Many strains of the above-mentioned microorganisms that are polyresistant to other antibiotics, such as aminopenicillins and ureidopenicillins, first-and second-generation cephalosporins, and aminoglycosides, are sensitive to ceftriaxone. Treponema pallidum is sensitive to ceftriaxone in vitro and in animal experiments. Clinical trials show that ceftriaxone has good efficacy against primary and secondary syphilis. With very few exceptions, clinical isolates of P. aeruginosa are resistant to ceftriaxone.

Anaerobesbacteroides spp. (bile-sensitive)*, Clostridium spp. (except C. difficile), Fusobacterium nucleatum, Fusobacterium spp. (other), Gaffkya anaerobica (formerly called Peptococcus), Peptostreptococcus.

*Some isolates of these species are resistant to ceftriaxone due to the formation of P-lactamases. Note. Many strains of p-lactamase-forming Bacteroides spp. (in particular, B. fragilis) are stable. Clostridium difficile is also resistant.

Sensitivity to ceftriaxone can be determined by the disco-diffusion method or by serial dilutions on agar or broth, using a standard technique similar to that recommended by the Institute of Clinical and Laboratory Standards (ICLS). The ICLS has established the following criteria for evaluating the results of a sample for ceftriaxone: :

Ceftriaxone discs should be used for determination, since in vitro studies have shown that ceftriaxone is active against individual strains that show resistance when using discs designed for the entire group of cephalosporins. Instead of ICLS standards, other well-standardized standards can be used to determine the sensitivity of microorganisms, for example, the German Institute for Standardization DIN (Deutsches Institut fur Normung) and the international recommendations of ICS (International Collaborative Study), which allow an adequate interpretation of the sensitivity state.

Pharmacokinetic Spharmakinetics of ceftriaxone is non-linear. All major pharmacokinetic parameters based on total drug concentrations, with the exception of the half-life, depend on the dose and increase in less than proportion to its increase. Non-linearity is typical for pharmacokinetic parameters that depend on the total concentration of ceftriaxone in blood plasma (not only free ceftriaxone), and is explained by saturation of the drug’s binding to plasma proteins.

Absorption The maximum plasma concentration after a single intramuscular injection of 1 g of the drug is about 81 mg / l and is reached within 2-3 hours after use. The areas under the plasma concentration – time curve after intravenous and intramuscular use are the same. This means that the bioavailability of ceftriaxone after intramuscular use is 100%.

After intravenous bolus use of 500 mg and 1 g of ceftriaxone, the mean maximum plasma concentrations were 120 mg / l and 200 mg/L, respectively. After an intravenous infusion of 500 mg,1 g and 2 g of ceftriaxone, the plasma concentrations of the drug were approximately 80,150 and 250 mg/l, respectively. After intramuscular injection, the average maximum concentration of ceftriaxone in blood plasma is approximately two times lower than after intravenous use of the equivalent dose of the drug.

Distributionthe volume of distribution of ceftriaxone is 7-12 liters. After use in a dose of 1-2 g, ceftriaxone penetrates well into tissues and body fluids. For more than 24 hours, its concentrations far exceed the minimum suppressive concentrations for most infectious agents in more than 60 tissues and fluids (including the lungs, heart, bile ducts, liver, tonsils, middle ear and nasal mucosa, bones, as well as spinal, pleural and synovial fluids and prostate secretions).

After intravenous use, ceftriaxone quickly penetrates into the cerebrospinal fluid, where bactericidal concentrations against sensitive microorganisms persist for 24 hours.

Protein binding: Myceftriaxone reversibly binds to albumin. The degree of binding is approximately 95% when the concentration of ceftriaxone in blood plasma is less than 100 mg/l. The proportion of ceftriaxone bound to plasma protein decreases with increasing concentration, since the binding is saturated and amounts to about 85% at concentrations of 300 mg/l.

Penetration into individual tissues Niceftriaxone penetrates through the meninges, to the greatest extent when they are inflamed. The average maximum concentration of ceftriaxone in the cerebrospinal fluid reaches 25% of the concentration of ceftriaxone in the blood plasma in patients with bacterial meningitis, and only 2% of the concentration in the blood plasma in patients with non-inflamed meninges. The maximum concentration of ceftriaxone in the cerebrospinal fluid is reached 4-6 hours after its intravenous use. Ceftriaxone passes through the placental barrier and enters breast milk in low concentrations.

Metabolism Ceftriaxone does not undergo systemic metabolism, but is converted to inactive metabolites by the action of intestinal microflora.

Elimination The total plasma clearance of ceftriaxone is 10-22 ml/min. Renal clearance is 5-12 ml / min. 50-60% of ceftriaxone is excreted unchanged by the kidneys, and 40-50% – unchanged by the intestines. The half-life of ceftriaxone in adults is about 8 hours.

Pharmacokinetics in special clinical casesnovebirths, children and children under 12 years of age in newborns, the half-life of ceftriaxone is increased compared to other age groups. In the first 14 days of life, the concentration of free ceftriaxone in blood plasma can be further increased due to low glomerular filtration and features of binding of the drug to plasma proteins. In paediatric patients, the elimination half-life is shorter than in newborns and adults.

Plasma clearance and volume of distribution of total ceftriaxone are higher in newborns, infants, and children under 12 years of age than in adults.

Impaired renal or hepatic functionin patients with impaired renal or hepatic function, the pharmacokinetics of ceftriaxone change slightly, there is only a slight increase in the half-life (less than 2 times), even in patients with severe renal insufficiency.

A slight increase in the half-life of ceftriaxone in renal insufficiency can be explained by a compensatory increase in non-renal clearance as a result of a decrease in the degree of binding to plasma proteins and a corresponding increase in the non-renal clearance of total ceftriaxone.

In patients with hepatic insufficiency, the elimination half-life does not increase. In such patients, a compensatory increase in renal clearance occurs. The reason is also an increase in the concentration of free ceftriaxone in the blood plasma, which contributes to a paradoxical increase in the total clearance of the drug against the background of an increase in the volume of distribution.

Senile patients In patients over 75 years of age, the elimination half-life is, on average, two or three times longer than in adult patients.

Indications

Infections caused by ceftriaxone-sensitive pathogens: sepsis; meningitis; disseminated Lyme disease (stages II and III of the disease); abdominal infections (peritonitis, biliary tract and gastrointestinal tract infections); infections of bones, joints, soft tissues, skin, and wound infections; infections in patients with weakened immune systems; kidney and urinary tract infections; respiratory tract infections, especially pneumonia, and ENT infections; genital infections. Perioperative prevention of infections.

Use during pregnancy and lactation

Pregnancy. Ceftriaxone penetrates the placental barrier. The safety of use during pregnancy in women has not been established. Preclinical studies of reproduction have not revealed any embryotoxic, fetotoxic, teratogenic effects or other adverse effects of the drug on male and female fertility, the process of childbirth, perinatal and postnatal fetal development. During pregnancy, especially in the first trimester, it should be prescribed only for strict indications, provided that the intended benefit to the mother exceeds the potential risk to the fetus. Breast-feeding period. In low concentrations, ceftriaxone passes into breast milk. Ceftriaxone is unlikely to have an effect on a breastfed child when used by the mother in therapeutic doses, however, the risk of diarrhea, fungal infections of the mucous membranes and hypersensitivity reactions in the child cannot be excluded. It is necessary to stop breastfeeding or stop / refrain from ceftriaxone therapy, taking into account the benefits of breastfeeding for the child and the benefits of therapy for the mother.

Contraindications

Hypersensitivity hypersensitivity to ceftriaxone and any other component of the drug. Hypersensitivity to cephalosporins. A history of severe hypersensitivity reactions (e. g., anaphylactic reactions) to other beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

Preterm children under the age of 41 weeks inclusive (total gestational and chronological age), the use of ceftriaxone is contraindicated.

Full-term newborns (less than 28 days of age)

• Hyperbilirubinemia, jaundice or acidosis, and hypoalbuminemia in newborns (in vitro studies have shown that ceftriaxone can displace bilirubin from binding to serum albumin, increasing the risk of bilirubin encephalopathy in such patients).
• Intravenous use of calcium-containing solutions to newborns. Newborns (≤ 28 days) who are already prescribed or are expected to receive intravenous treatment with calcium-containing solutions, including prolonged calcium-containing infusions, for example, with parenteral nutrition, due to the risk of precipitation of ceftriaxone calcium salts (see sections “Dosage and use” and “Interaction with other drugs”). Isolated fatal cases of precipitation in the lungs and kidneys in newborns treated with ceftriaxone and calcium-containing solutions are described. At the same time, in some cases, one venous approach was used, and the formation of precipitates was observed directly in the system for intravenous use, and at least one fatal case was described with different venous approaches and at different times of use of ceftriaxone and calcium-containing solutions. Such cases were observed only in newborns (see the section “Post-marketing surveillance”).

With caution

Breast-feeding period. A history of mild hypersensitivity reactions to other beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

Side effects

The most common adverse reactions reported during ceftriaxone therapy in clinical trials are eosinophilia, leukopenia, thrombocytopenia, diarrhea, rash, and increased liver enzyme activity.

The following classification is used to describe the frequency of adverse reactions: very frequent (≥ 1/10), frequent (≥ 1/100 and <1/10), infrequent (≥1/1000 and < 1/100), rare (≥ 1/10000 and <1/1000) and very rare (

Adverse reactions are grouped according to the classes of organ systems in the MedDRA Regulatory Dictionary.

Infectious and parasitic diseases: infrequently-mycoses of the genital organs; rarely-pseudomembranous colitis.

Disorders of the blood and lymphatic system: often – eosinophilia, leukopenia, thrombocytopenia; infrequently-granulocytopenia, anemia, coagulopathy.

Nervous system disorders: infrequently – headache and dizziness.

Respiratory, thoracic and mediastinal disorders: rarely-bronchospasm.

Disorders of the gastrointestinal tract: often – diarrhea, loose stools; infrequently-nausea, vomiting.

Liver and biliary tract disorders: often-increased activity of liver enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase (ALP)).

Skin and subcutaneous tissue disorders: often-rash; infrequently-pruritus; rarely-urticaria.

Kidney and urinary tract disorders: rarely – hematuria, glucosuria.

General disorders and disorders at the injection site: infrequently – phlebitis, pain at the injection site, fever; rarely-swelling, chills.

Influence on the results of laboratory and instrumental studies: infrequently-an increase in the concentration of creatinine in the blood.

Post-registration monitoring

Side effects observed with the use of ceftriaxone in the post-marketing period are described below. Determining the frequency of observed adverse events, as well as their association with the use of ceftriaxone, is not always possible, since it is impossible to determine the exact size of the patient population.

Disorders of the gastrointestinal tract: pancreatitis, stomatitis, glossitis, taste disorders.

Disorders of the blood and lymphatic system: thrombocytosis, increased thromboplastin and prothrombin time, decreased prothrombin time, hemolytic anemia. Individual cases of agranulocytosis are described (

Immune system disorders: anaphylactic shock, hypersensitivity.

Skin and subcutaneous tissue disorders: acute generalized exanthematous pustulosis, isolated cases of severe adverse reactions (exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome)).

Nervous system disorders: convulsions.

Hearing disorders and labyrinth disorders: vertigo.

Infectious and parasitic diseases: superinfections.

The following adverse reactions are also known: formation of ceftriaxone calcium salt precipitates in the gallbladder with appropriate symptoms, bilirubin encephalopathy, hyperbilirubinemia, oliguria, vaginitis, increased sweating, hot flashes, allergic pneumonitis, nosebleeds, jaundice, palpitation, serum sickness, and anaphylactic or anaphylactoid reactions.

Separate fatal cases of precipitate formation in the lungs and kidneys are described based on autopsy results in newborns treated with ceftriaxone and calcium-containing solutions. In some cases, a single venous approach was used, and the formation of precipitates was observed directly in the system for intravenous use. At least one fatal case has also been reported with different venous approaches and at different times of use of ceftriaxone and calcium-containing solutions. At the same time, according to the results of an autopsy study, no precipitates were found in this newborn. Such cases were observed only in newborns (see the section “Special instructions”).

Cases of ceftriaxone precipitate formation in the urinary tract have been reported, mainly in children who received either large daily doses of the drug (≥ 80 mg/kg per day), or cumulative doses of more than 10 g, and who also had additional risk factors (dehydration, bed rest). The formation of precipitates in the kidneys can be asymptomatic or clinically manifested, can lead to ureteral obstruction and postrenal acute renal failure. This adverse event is reversible and disappears after discontinuation of ceftriaxone therapy.

General disorders and disorders at the injection site: phlebitis after intravenous use. It can be avoided by injecting the drug slowly for 5 minutes, preferably into a large vein.

Effects on laboratory analyseswhen treated with ceftriaxone, patients may have false-positive Coombs test results. Like other antibiotics, ceftriaxone can give a false positive test result for galactosemia. False positive results can also be obtained when determining glucose in the urine by non-enzymatic methods, therefore, during therapy with ceftriaxone, glucosuria, if necessary, should be determined only by the enzyme method.

Ceftriaxone may cause an unreliable decrease in the glycemic values obtained with some blood glucose monitoring devices. See the instructions in the instructions for use of the device used.If necessary, alternative methods for determining blood glucose should be used.

Interaction

Concomitant use of high doses of ceftriaxone and “loop” diuretics (for example, furosemide) did not cause renal dysfunction. There are conflicting data on the likelihood of increased nephrotoxicity of aminoglycosides when used with cephalosporins, so it is necessary to monitor renal function and the concentration of aminoglycosides in the blood. Alcohol consumption after ceftriaxone use was not accompanied by a disulfiram-like reaction. Ceftriaxone does not contain the N-methylthiotetrazole group, which could cause ethanol intolerance and bleeding, which is inherent in some other cephalosporins.

Probenecid does not affect the elimination of ceftriaxone.

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

Antagonism between chloramphenicol and ceftriaxone was found in vitro.

Do not use calcium-containing solvents, such as Ringer’s solution or Hartmann’s solution, when preparing ceftriaxone solutions for intravenous use and their subsequent dilution, because of the possible formation of precipitates.

The formation of ceftriaxone calcium salt precipitates can also occur when ceftriaxone and calcium-containing solutions are mixed using a single venous approach. Do not use ceftriaxone simultaneously with calcium-containing solutions for intravenous use, including with prolonged infusions of calcium-containing solutions, for example, with parenteral nutrition using the Y-connector. For all groups of patients, except newborns, sequential use of ceftriaxone and calcium-containing solutions is possible, with careful flushing of the infusion systems between infusions with a compatible liquid. To assess the interaction of ceftriaxone and calcium, two in vitro studies were conducted: one using adult blood plasma, the other using umbilical cord blood plasma of a newborn. Various combinations of ceftriaxone with an initial concentration of up to 1 mM (the maximum concentration that ceftriaxone reaches in vivo with an infusion of 2 g of the drug for at least 30 minutes) and calcium with an initial concentration of up to 12 mM (48 mg/dl) were analyzed. A decrease in the concentration of ceftriaxone in plasma was observed when using calcium at a concentration of 6 mM (24 mg / dl) or higher for adult plasma and at a concentration of 4 mM (16 mg/dl) or higher for neonatal plasma, which indicates an increased risk of formation of ceftriaxone calcium salts in newborns (see sections “Dosage and use”, “Contraindications”).

Ceftriaxone is pharmacologically incompatible with amsacrine, vancomycin, fluconazole and aminoglycosides.

When using vitamin K antagonists on the background of ceftriaxone therapy, the risk of bleeding increases. Blood clotting parameters should be constantly monitored and, if necessary, the anticoagulant dose adjusted both during and after the end of ceftriaxone therapy.

Synergy between ceftriaxone and aminoglycosides has been shown for many gram-negative bacteria. Although the increased effectiveness of such combinations is not always predictable, it should be taken into account in severe, life-threatening infections, such as those caused by Pseudomonas aeruginosa/

How to take, course of use and dosage

Standard dosage regimen: intravenous, infused.

Adults and children over 12 years of age ≥ 50 kg: 1-2 g once a day (every 24 hours). In severe cases or for infections with only moderate sensitivity to ceftriaxone, the daily dose can be increased to 4 g.

The duration of treatment depends on the course of the disease. As always with antibiotic therapy, the use of ceftriaxone should be continued for at least 48 to 72 hours after normalization of temperature and confirmation of eradication of the pathogen. Usually, the course of treatment is 4-14 days; for complicated infections, a longer use may be required.

The course of treatment for Streptococcus pyogenes infections should be at least 10 days.

Introduction The general rule should be to use solutions immediately after preparation.

The intravenous infusion should last at least 30 minutes. To prepare the solution, dilute 2 g of ceftriaxone in 40 ml of one of the following infusion solutions that do not contain calcium ions: 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% hydroxyethyl starch solution, water for injection. Ceftriaxone solutions should not be mixed or added to solutions containing other antimicrobials or other solvents other than those listed above, due to possible incompatibilities.

Do not use calcium-containing solvents, such as Ringer’s solution or Hartmann’s solution, for the preparation of intravenous ceftriaxone solutions and their subsequent dilution, because of the possible formation of precipitates.

The formation of ceftriaxone calcium salt precipitates can also occur when ceftriaxone is mixed with calcium-containing solutions using a single venous approach. Do not use ceftriaxone simultaneously with calcium-containing solutions for intravenous use, including with prolonged infusions of calcium-containing solutions, for example, with parenteral nutrition using the Y-connector. For all groups of patients, except newborns, sequential use of ceftriaxone and calcium-containing solutions is possible, with careful flushing of the infusion systems between infusions with a compatible liquid (see the section “Interaction with other drugs”).

There have been no reports of interactions between ceftriaxone and oral calcium-containing drugs or interactions between ceftriaxone for intramuscular use and calcium-containing solutions (for intravenous or oral use).

Dosage in special cases of patients with impaired liver functionin patients with impaired liver function, there is no need to reduce the dose, provided that there are no violations of renal function.

Patients with impaired renal function patients with impaired renal function do not need to reduce the dose if there is no impaired liver function. The daily dose of ceftriaxone should not exceed 2 g only in cases of renal insufficiency with a creatinine clearance of less than 10 ml / min. Ceftriaxone is not eliminated during hemodialysis or peritoneal dialysis, so an additional dose of ceftriaxone is not required after the end of dialysis.

In combination with severe renal and hepatic insufficiency, the effectiveness and safety of the drug should be carefully monitored.

Elderly and senile patients The usual adult doses are not adjusted for age, provided that there is no severe renal or hepatic insufficiency.

Newborn infants, children and children under 12 years of age When prescribing ceftriaxone once a day, it is recommended to adhere to the following dosage regimens:

• children (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, children and children (aged from 15 days to 12 years): 20 – 80 mg/kg of body weight once a day;
• children with body weight over 50 kg are prescribed the adult dosage.

Ceftriaxone is contraindicated in premature children under 41 weeks of age (total gestational and chronological age).

Ceftriaxone is contraindicated in newborns (≤ 28 days) who are already prescribed or are expected to receive intravenous treatment with calcium-containing solutions, including prolonged calcium-containing infusions, for example, with parenteral nutrition due to the risk of precipitation of ceftriaxone calcium salts (see section “Contraindications”).

In children and children under 12 years of age, intravenous doses of 50 mg / kg or higher should be administered dropwise for at least 30 minutes. In newborns, intravenous use should be performed within 60 minutes to reduce the potential risk of developing bilirubin encephalopathy.

Meningitis In case of bacterial meningitis in children and young children, treatment begins 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 meningococcal meningitis were achieved with a treatment duration of 4 days, in meningitis caused by Haemophilus influenzae-6 days, and Streptococcus pneumoniae-7 days.

Lyme disease%^%50 mg / kg (highest daily dose – 2 g) for adults and children once a day for 14 days.

Prevention of postoperative infectionsdepending on the degree of infectious risk,1-2 g of ceftriaxone is administered once 30-90 minutes before the operation. Simultaneous (but separate, see the section “Dosage and use”) use of ceftriaxone and one of the 5-nitroimidazoles, for example, ornidazole, is well proven in operations on the colon and rectum. Standard dosage regimen

Intravenously, by infusion.

Adults and children over 12 years of age ≥ 50 kg: 1-2 g once a day (every 24 hours). In severe cases or for infections with only moderate sensitivity to ceftriaxone, the daily dose can be increased to 4 g.

The duration of treatment depends on the course of the disease. As always with antibiotic therapy, the use of ceftriaxone should be continued for at least 48 to 72 hours after normalization of temperature and confirmation of eradication of the pathogen.Usually, the course of treatment is 4-14 days; for complicated infections, a longer use may be required.

The course of treatment for Streptococcus pyogenes infections should be at least 10 days.

Introduction The general rule should be to use solutions immediately after preparation.

The intravenous infusion should last at least 30 minutes. To prepare the solution, dilute 2 g of ceftriaxone in 40 ml of one of the following infusion solutions that do not contain calcium ions: 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% hydroxyethyl starch solution, water for injection. Ceftriaxone solutions should not be mixed or added to solutions containing other antimicrobials or other solvents other than those listed above, due to possible incompatibilities.

Do not use calcium-containing solvents, such as Ringer’s solution or Hartmann’s solution, for the preparation of intravenous ceftriaxone solutions and their subsequent dilution, because of the possible formation of precipitates.

The formation of ceftriaxone calcium salt precipitates can also occur when ceftriaxone is mixed with calcium-containing solutions using a single venous approach. Do not use ceftriaxone simultaneously with calcium-containing solutions for intravenous use, including with prolonged infusions of calcium-containing solutions, for example, with parenteral nutrition using the Y-connector. For all groups of patients, except newborns, sequential use of ceftriaxone and calcium-containing solutions is possible, with careful flushing of the infusion systems between infusions with a compatible liquid (see the section “Interaction with other drugs”).

There have been no reports of interactions between ceftriaxone and oral calcium-containing drugs or interactions between ceftriaxone for intramuscular use and calcium-containing solutions (for intravenous or oral use).

Dosage in special cases of patients with impaired liver functionin patients with impaired liver function, there is no need to reduce the dose, provided that there are no violations of renal function.

Patients with impaired renal function patients with impaired renal function do not need to reduce the dose if there is no impaired liver function. The daily dose of ceftriaxone should not exceed 2 g only in cases of renal insufficiency with a creatinine clearance of less than 10 ml / min. Ceftriaxone is not eliminated during hemodialysis or peritoneal dialysis, so an additional dose of ceftriaxone is not required after the end of dialysis.

In combination with severe renal and hepatic insufficiency, the effectiveness and safety of the drug should be carefully monitored.

Elderly and senile patients The usual adult doses are not adjusted for age, provided that there is no severe renal or hepatic insufficiency.

Newborn infants, children and children under 12 years of age When prescribing ceftriaxone once a day, it is recommended to adhere to the following dosage regimens:

• children (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, children and children (aged from 15 days to 12 years): 20 – 80 mg/kg of body weight once a day;
• children with body weight over 50 kg are prescribed the adult dosage.

Ceftriaxone is contraindicated in premature children under 41 weeks of age (total gestational and chronological age).

Ceftriaxone is contraindicated in newborns (≤ 28 days) who are already prescribed or are expected to receive intravenous treatment with calcium-containing solutions, including prolonged calcium-containing infusions, for example, with parenteral nutrition due to the risk of precipitation of ceftriaxone calcium salts (see section “Contraindications”).

In children and children under 12 years of age, intravenous doses of 50 mg / kg or higher should be administered dropwise for at least 30 minutes. In newborns, intravenous use should be performed within 60 minutes to reduce the potential risk of developing bilirubin encephalopathy.

Meningitis In case of bacterial meningitis in children and young children, treatment begins 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 meningococcal meningitis were achieved with a treatment duration of 4 days, in meningitis caused by Haemophilus influenzae-6 days, and Streptococcus pneumoniae-7 days.

Lyme disease 50 mg / kg (highest daily dose – 2 g) for adults and children once a day for 14 days.

Prevention of postoperative infectionsdepending on the degree of infectious risk,1-2 g of ceftriaxone is administered once 30-90 minutes before the operation. Simultaneous (but separate, see the section “Dosage and use”) use of ceftriaxone and one of the 5-nitroimidazoles, for example, ornidazole, is well proven in operations on the colon and rectum.

Overdose

Symptoms: nausea, vomiting, and diarrhea. Treatment: in case of overdose, hemodialysis and peritoneal dialysis are not effective. There is no specific antidote; treatment is symptomatic.

Special instructions

Hypersensitivity reactions As with other beta-lactam antibiotics, severe hypersensitivity reactions, including fatal ones, have been reported. If a severe hypersensitivity reaction develops, ceftriaxone therapy should be immediately discontinued and appropriate urgent treatment measures should be taken. Before starting ceftriaxone therapy, it is necessary to determine whether the patient has experienced hypersensitivity reactions to ceftriaxone, cephalosporins, or severe hypersensitivity reactions to other beta-lactam antibiotics (penicillins, monobactams, and carbapenems).

Caution should be exercised when using ceftriaxone in patients with a history of mild hypersensitivity reactions to other P-lactam antibiotics (penicillins, monobactams, and carbapenems).

Sodium Content 1 g of ceftriaxone contains 3.6 mmol of sodium. This should be taken into account in patients on a sodium-controlled diet.

Hemolytic anaemia As with other cephalosporins, autoimmune hemolytic anaemia may occur when treated with ceftriaxone. Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported. If a patient receiving ceftriaxone develops anemia, the diagnosis of cephalosporin-associated anemia cannot be excluded and treatment should be discontinued until the cause is determined.

Clostridium difficile diarrhoea As with most other antibacterial agents, cases of Clostridium difficile (C. difficile) diarrhoea of varying severity, ranging from mild diarrhoea to fatal colitis, have been reported with ceftriaxone. Treatment with antibacterial drugs suppresses the normal microflora of the colon and provokes the growth of C. difficile. In turn, C. difficile forms toxins A and B, which are factors in the pathogenesis of diarrhea caused by C. difficile. C. difficile strains that produce toxins are infectious agents with a high risk of complications and mortality due to their possible resistance to antimicrobial therapy, and treatment may require colectomy. All patients with diarrhea after antibiotic therapy should be aware of the possibility of developing diarrhea caused by C. difficile. A thorough medical history should be collected, as cases of C. difficile-induced diarrhea have been reported more than 2 months after antibiotic therapy. If C. difficile-induced diarrhea is suspected or confirmed, current non-C. difficile-directed antibiotic therapy may need to be discontinued. In accordance with the clinical indications, appropriate treatment should be prescribed with the introduction of fluids and electrolytes, proteins, antibiotic therapy against C. difficile, and surgical treatment. Do not use medications that inhibit intestinal motility.

Superinfectionsas with treatment with other antibacterial drugs, superinfections may develop.

Changes in prothrombin timein patients treated with ceftriaxone, rare cases of changes in prothrombin time have been described. Patients with vitamin K insufficiency (impaired synthesis, nutritional disorders) may need to monitor prothrombin time during therapy and prescribe vitamin K (10 mg/week) with an increase in prothrombin time before or during therapy.

Formation of Ceftriaxone calcium salt precipitates Cases of fatal reactions resulting from the deposition of ceftriaxone-calcium precipitates in the lungs and kidneys of newborns have been described. Theoretically, there is a possibility of interaction of ceftriaxone with calcium-containing solutions for intravenous use and in other age groups of patients, so ceftriaxone should not be mixed with calcium-containing solutions (including for parenteral nutrition), as well as administered simultaneously, including through separate accesses for infusions at different sites. Theoretically, based on the calculation of 5 half-lives of ceftriaxone, the interval between use of ceftriaxone and calcium-containing solutions should be at least 48 hours.Data on the possible interaction of ceftriaxone with calcium-containing drugs for oral use, as well as ceftriaxone for intramuscular use with calcium-containing drugs (intravenously or orally) are not available. After the use of ceftriaxone, usually in doses exceeding the standard recommended (1 g per day or more), ultrasound examination of the gallbladder revealed precipitation of ceftriaxone calcium salt, the formation of which is most likely in children. Precipitates rarely show any symptoms and disappear after completion or discontinuation of ceftriaxone therapy. If these phenomena are accompanied by clinical symptoms, conservative non-surgical treatment is recommended, and the decision to discontinue the drug is left to the discretion of the attending physician and should be based on an individual assessment of the benefit and risk.

Despite the presence of data on the formation of intravascular precipitates only in newborns when using ceftriaxone and calcium-containing infusion solutions or any other calcium-containing drugs, ceftriaxone should not be mixed or prescribed to children and adult patients simultaneously with calcium-containing infusion solutions, even using different venous approaches (see sections “Contraindications”, “Interaction with other drugs”, subsection “Post-marketing surveillance”).

Rare cases of pancreatitis, possibly due to obstruction of the biliary tract, have been described in patients treated with ceftriaxone. Most of these patients already had risk factors for biliary tract congestion, such as previous therapy, severe illnesses, and full parenteral nutrition. At the same time, it is impossible to exclude the triggering role of biliary tract precipitates formed under the influence of ceftriaxone in the development of pancreatitis.

Use in children The safety and efficacy of ceftriaxone in newborns, children and young children were determined for the dosages described in the section “Dosage and use”. Studies have shown that, like other cephalosporins, ceftriaxone can displace bilirubin from binding to serum albumin. Ceftriaxone should not be used in newborns, especially premature infants, who are at risk of developing bilirubin encephalopathy (see the section “Contraindications”).

Long-term treatmentin long-term treatment, it is necessary to regularly monitor the picture of peripheral blood, indicators of the functional state of the liver and kidneys.

Blood test monitoring: A complete blood test should be performed regularly during long-term treatment.

Serological studiesin the treatment with ceftriaxone, false positive results of the Coombs test, galactosemia test, when determining glucose in the urine can be noted (glucosuria is recommended to be determined only by the enzymatic method).

Influence on the ability to drive vehicles and mechanisms

There are no data indicating the effect of the drug on driving vehicles and working with machines and mechanisms. However, during therapy with ceftriaxone, caution should be exercised when driving vehicles and working with mechanisms due to the possibility of dizziness and other adverse reactions that may affect the ability to drive vehicles, mechanisms.

Storage conditions

In a dark place at a temperature not exceeding 25 °C. Keep out of reach of children.

Shelf

life is 2 years. Do not use after the expiration date

Active ingredient

Ceftriaxone

Conditions of release from pharmacies

By prescription

Dosage form

solution for injection and infusion