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

One bottle contains: active substance: ceftriaxone in the form of ceftriaxone sodium salt - 0.5 g or 1.0 g, calculated on an anhydrous substance - 0.5395 g or 1.0790 g.

Description:Almost white or yellowish crystalline powder.

Pharmacotherapeutic group:Antibiotic-cephalosporin

ATX: & nbsp

J.01.D.D.04 Ceftriaxone

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 of action against Gram-negative and Gram-positive microorganisms. It is highly resistant to most β-lactamases (both penicillinases and cephalosporinases) produced by gram-positive and gram-negative bacteria.

Ceftriaxone is usually active against the following microorganisms.

Gram-positive aerobes

Staphylococcus aureus (methicillin-sensitive), coagulase-negative staphylococci, Streptococcus pyogenes β-hemolytic, groups A), Streptococcus agalactiae β-hemolytic, group B), β-hemolytic streptococci (groups of neither A nor B), Streptococcus viridans, Streptococcus pneumoniae.

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 Iwofii, Acinetobacter anitratus (mainly, A. baumannii), Aeromonas hydrophila, Alcaligenes faecalis, Alcaligenes odorans, alkaligen-like bacteria, Borrelia burgdorferi, Capnocytophaga spp., Citrobacter diversus (including C. amalonaticus), Citrobacter freundif, 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. (aboutchi), Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Plesiomonas shigelloides, Proteus mirabilis, Proteus penner *, Proteus vulgaris * Pseudomonas fluorescens * Pseudomonas spp. (aboutchi), Providencia rettger * Providencia spp. (other), Salmonella typhi, Salmonella spp. (non-phytophoid), Serratia marcescens * Serratia spp. (other)⁴, Shigella spp., Vibrio spp., Yersinia enterocolitica, Yersinia spp. (other).

* 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, multiresistant to other antibiotics, such as aminopenicillins and ureidopenicillins,cephalosporins of the first and second generation 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 R. aeruginosa resistant to ceftriaxone.

Anaerobes

Bacteroides spp. (bile-sensitive) *, Clostridium spp. (Besides FROM. difficile), Fusobacterium nucleatum, Fusobacterium spp. (other), Gaffkya anaerobica (before called Peptococcus), Peptostreptococcus spp.

* Some isolates these species are stable to ceftriaxone of-behind educationthe β-lactamase.

Note. Many strains of (3-lactamase-forming Bacteroides spp. (in particular, V. fragilis) are stable. Stable and Clostridium difficile. Sensitivity to ceftriaxone can be determined by disc-diffusion method or serial dilution method on agar or broth, using a standard procedure similar to that recommended by the Institute of Clinical and Laboratory Standards (ICLS). The FCS has established the following criteria for evaluating the results of a sample for ceftriaxone:

Sensitive

Moderately sensitive

Stable

Method of dilution The overwhelming concentration, mg / l

16-32

=64

Disc method (disc with 30 μg ceftriaxone)

The diameter of the growth retardation zone,

=21

20-14

=13

To determine, CDs with ceftriaxone should be taken, as in in vitro studies it has been shown that ceftriaxone is active against individual strains that show resistance when using discs intended 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 Deutsche Institut für Normung (DIN) and international ICS (International Collaborative Study) recommendations that adequately interpret the state of sensitivity.

Pharmacokinetics:

The pharmacokinetics of ceftriaxone is non-linear. All the main pharmacokinetic parameters based on the total concentrations of the drug, except for the half-life, depend on the dose and increase less than proportionally to its increase. Nonlinearity is characteristic for pharmacokinetic parameters, depending on the total concentration of ceftriaxone in the blood plasma (not only free ceftriaxone), and is explained by the saturation of the binding of the drug with plasma proteins.

Suction

The maximum concentration in the plasma after a single intramuscular injection of 1 g of the drug is about 81 mg / l and is achieved within 2-3 hours after administration. The area under the curve "concentration in plasma - time" after intravenous and intramuscular injection is the same. This means that the bioavailability of ceftriaxone after intramuscular injection is 100%.

After an intravenous bolus injection of 0.5 g and 1 g of ceftriaxone, the mean maximum plasma concentration was 120 mg / L and 200 mg / L, respectively. After intravenous infusion of 0.5 g, 1 g and 2 g of ceftriaxone, the concentration of the drug in the blood plasma was approximately 80, 150 and 250 mg / l, respectively. After intramuscular injection, the mean maximum plasma concentration of ceftriaxone twice as low as after intravenous administration of an equivalent dose of the drug.

Distribution

The volume of distribution of ceftriaxone is 7-12 liters. After a dose of 1-2 g ceftriaxone well penetrates into tissues and body fluids. For more than 24 hours, its concentrations far exceed the minimum inhibitory 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 cerebrospinal, pleural and synovial fluids and secretion of the prostate gland).

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

Binding to proteins

Ceftriaxone reversibly binds to albumin. The degree of binding is approximately 95% for ceftriaxone concentrations in blood plasma of less than 100 mg / l. The fraction of the blood plasma associated with ceftriaxone decreases with increasing concentration, since the binding is saturated and is about 85% at a concentration of 300 mg / l.

Penetration into separate tissues

Ceftriaxone penetrates through the meninges, most of all with their inflammation. 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 % from the concentration in the blood plasma in patients with non-inflamed dura mater. The maximum concentration of ceftriaxone in the cerebrospinal fluid is reached 4-6 hours after its intravenous administration. Ceftriaxone passes through the placental barrier and in small concentrations falls into the breast milk.

Metabolism

Ceftriaxone is not subject to systemic metabolism, but is converted to inactive metabolites under the influence of intestinal microflora.

Excretion

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

Pharmacokinetics in special clinical cases

Newborns, infants 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 the blood plasma can be further increased due to low glomerular filtration and the peculiarities of binding the drug to plasma proteins. In pediatric patients, the half-life is less than in newborns and adults. The values of plasma clearance and the volume of distribution of total ceftriaxone are higher in newborns, infants and children under 12 years compared with those in adults.

Violation of the function of nochek or liver

In patients with impaired renal or hepatic function, the pharmacokinetics of ceftriaxone varies insignificantly, only a small increase in the half-life (less than 2-fold) is observed even in patients with severe renal insufficiency. A slight increase in the half-life of ceftriaxone in renal insufficiency can be explained by compensatory increase in non-spot clearance as a result of decreased binding to plasma proteins and a corresponding increase in the chain clearance of total ceftriaxone.

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

Patients of senile age

In patients older than 75 years, the elimination half-life is, on average, two or three times greater than in adult patients.

Indications:

Infections caused by susceptible to ceftriaxone pathogens: sepsis; meningitis; disseminated Lyme disease (stage II and III disease); infection of the abdominal cavity (peritonitis,infections of the biliary tract and gastrointestinal tract); infection of bones, joints, soft tissues, skin, as well as wound infections; infection in patients with weakened immunity; infections of the kidneys and urinary tract; infections of the respiratory tract, especially pneumonia, and infections of the ENT organs; infections of the genitals, including gonorrhea.

Perioperative infection prevention.

Contraindications:

Hypersensitivity

Hypersensitivity to ceftriaxone and any other component of the drug.

Hypersensitivity to cephalosporins.

Severe hypersensitivity reactions (for example, anaphylactic reactions) to other β-lactam antibiotics (penicillins, monobactams and carbapenems) in the anamnesis.

Premature babies

Preterm infants up to 41 weeks of age (cumulative gestational age and chronological age) are not eligible for ceftriaxone.

Completed newborns (≤28-day-olds)

- Hyperbilirubinemia, jaundice or acidosis, hypoalbuminemia in newborns (studies in vitro showed that ceftriaxone can displace bilirubin from the association with serum albumin,increasing the risk of developing bilirubin encephalopathy in such patients).

- Intravenous administration of calcium-containing solutions to newborns. Newborns (≤28 days), which is already assigned or assumed intravenous treatment with calcium-containing solutions including calcium containing prolonged infusion, e.g., with parenteral nutrition, due to the formation of precipitates of calcium salts risk ceftriaxone (see. The sections "Dosage and Administration" and "Interaction with other drugs ").

Some fatal cases of the formation of precipitates in the lungs and kidneys in newborns who have received ceftriaxone and calcium-containing solutions. In some cases, one venous access was used, and the formation of precipitates was observed directly in the system for intravenous administration, and at least one fatal case with different venous accesses and at different times of administration of ceftriaxone and calcium-containing solutions was also reported. Similar cases were observed only in newborns (see subsection "Post-registration surveillance").

Lidocaine

Before carrying out intramuscular injection of ceftriaxone with lidocaine, it is necessary to exclude the presence of contraindications to lidocaine. Contraindications to the use of lidocaine are given in the instructions for the medical use of lidocaine. Ceftriaxone solutions containing lidocaine, can not be administered intravenously.

Carefully:

Breastfeeding period.

Not severe hypersensitivity reactions to other β-lactam antibiotics (penicillins, monobactams and carbapenems) in the anamnesis.

Pregnancy and lactation:

Pregnancy

Ceftriaxone penetrates the placental barrier. Safety of use in pregnancy in women is not established. Preclinical studies of reproductive performance have not revealed embryotoxic, fetotoxic, teratogenic effects or other adverse effects of the drug on the fertility of males and females, the process of labor, perinatal and postnatal fetal development. In pregnancy, especially in the first trimester, should be prescribed only on strict indications, provided that the intended benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

In low concentrations ceftriaxone enters the breast milk. It is unlikely that ceftriaxone will affect a breastfeeding baby when it is used by the mother in therapeutic doses, however, the risk of diarrhea, fungal infections of the mucous membranes and hypersensitivity reactions in the child can not be ruled out. It is necessary to stop breastfeeding or stop / refrain from ceftriaxone therapy, taking into account the benefits of breastfeeding for the baby and the benefits of therapy for the mother.

Dosing and Administration:

Standard dosing regimen

Intravenous, intramuscular.

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

Duration of treatment depends on the course of the disease. As always with antibiotic therapy, the administration of the drug Ceftriaxone should continue the patient for at least 48-72 hours after the normalization of temperature and confirmation of eradication of the pathogen.

Usually the course of treatment is 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.

Introduction

Use only freshly prepared solutions.

For intramuscular injection: 0.5 g of the drug is dissolved in 2 ml, and 1 g - in 3.6 ml of water for injection or 1% solution of lidocaine. To reduce pain with intramuscular injections, the drug should be administered with a 1% solution of lidocaine. The drug should be injected deeply intramuscularly into a sufficiently large muscle (buttock). Do not administer more than 1 g of the same muscle. The solution containing lidocaine, can not be administered intravenously.

For intravenous bolus administration: 0.5 g of the drug is dissolved in 5 ml, and 1 g - in 10 ml of water for injection. The solution is administered intravenously slowly for 5 minutes, preferably in a large vein.

For intravenous infusion: the solution is administered for at least 30 minutes.

2 g of the drug is dissolved in 40 ml of water for injection or one of the solutions that do not contain calcium (for example, 0.9% sodium chloride solution, 5 % or 10% dextrose solution, water for injections). Drug solutions Ceftriaxone can not be mixed or added to solutions containing other antimicrobial agents or other solvents, with the exception of those listed above, because of the possible incompatibility.

Can not be used to prepare solutions of the drug Ceftriaxone for intravenous administration and subsequent dilution, solvents containing calcium, such as Ringer's solution or Hartmann's solution, because of the possible formation of precipitates.

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

Dosing in special cases

Patients with impaired hepatic function

In patients with impaired liver function, there is no need to reduce the dose provided there are no violations of kidney function.

Patients with impaired renal function

In patients with impaired renal function, there is no need to reduce the dose provided there are no violations of liver function. Daily dose of the drug Ceftriaxone should not exceed 2 g only in cases of renal failure with creatinine clearance less than 10 ml / min. Ceftriaxone is not excreted in hemodialysis or peritoneal dialysis, so the patient is given an additional dose of the drug Ceftriaxone after the end of dialysis is not required.

When combination of severe renal and hepatic insufficiency should carefully monitor the effectiveness and safety of the drug.

Patients of elderly and senile age

Usual doses for adults without age adjustments, provided there is no severe renal and hepatic insufficiency.

Children

Newborns, infants and children under 12 years of age

When the drug is prescribed Ceftriaxone Once a day, it is recommended to adhere to the following dosing regimens:

- newborns (up to 14 days): 20-50 mg / kg body weight once a day; 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;

- Children weighing over 50 kg are prescribed doses for adults. Preterm infants up to 41 weeks of age (cumulative gestational age and chronological age) are not eligible for ceftriaxone.

Ceftriaxone is contraindicated in neonates (≤28 days), which is already assigned or assumed intravenous treatment with calcium-containing solutions including calcium containing prolonged infusion, e.g., with parenteral nutrition due to risk of formation of precipitates of calcium salts ceftriaxone (see. The section "Contraindications").For infants and children under 12 years of age, intravenous doses of 50 mg / kg or higher should be given drip for at least 30 minutes. Newborn intravenous administration should be performed within 60 minutes to reduce the potential risk of developing bilirubin encephalopathy.

Meningitis

When bacterial meningitis in infants and young children treatment starts with a dose of 100 mg / kg (but not more than 4 g) 1 time per day. After identifying the pathogen and determining its sensitivity, the dose can be reduced accordingly. The best results with meningococcal meningitis were achieved with a treatment duration of 4 days, with meningitis caused by Haemophilus influenzae - 6 days, Streptococcus pneumoniae - 7 days.

Lyme disease

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

Gonorrhea (caused by penicillinase-forming and penicillinase-forming strains).

Single intramuscular injection of 250 mg of the drug Ceftriaxone adult patients and children over 12 years ≥50 kg.

Acute otitis media

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

Adults are recommended a single intramuscular injection in a dose of 1-2 g.According to limited data, in severe cases or with ineffectiveness of previous therapy, the drug Ceftriaxone can be effective when administered intramuscularly at a dose of 1-2 g per day for 3 days.

Prevention of postoperative infections

Depending on the degree of infectious risk, 1-2 g of the drug Ceftriaxone once for 30-90 minutes before the operation. In operations on the colon and rectum, a simultaneous (but separate, see section "Method of administration and dose") is well established, the administration of the drug Ceftriaxone and one of 5-nitroimidazoles, for example, ornidazole.

Side effects:

The most frequent adverse reactions recorded with ceftriaxone in clinical trials are eosinophilia, leukopenia, thrombocytopenia, diarrhea, rash, and an increase in hepatic enzyme activity.

To describe the frequency of undesired reactions, the following classification is used: 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 (<1/10000), including isolated cases.

Undesirable reactions are grouped according to the classes of systems of the medical dictionary authorities for the regulatory activities of MedDRA.

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

Disturbances from the blood system and lymphatic system: often - eosinophilia, leukopenia, thrombocytopenia; infrequently - granulocytopenia, anemia, coagulopathy.

Impaired nervous system: infrequently - headache and dizziness.

Disturbances from the respiratory system, chest and mediastinal organs: rarely - bronchospasm.

Disorders from the gastrointestinal tract: often diarrhea, unformed stool; infrequently - nausea, vomiting.

Disorders from the liver and bile ducts: often - increased activity of hepatic enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), alkaline phosphatase (alkaline phosphatase)).

Disturbances from the skin and subcutaneous tissues: often - a rash; infrequently itching; rarely - hives.

Disorders from the kidneys and urinary tract: rarely - hematuria, glucosuria.

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

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

Post-Business Monitoring

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

Disorders from the gastrointestinal tract: pancreatitis, stomatitis, glossitis, taste disorder.

Disturbances from the blood system and lymphatic system: thrombocytosis, increased thromboplastin and prothrombin time, decreased prothrombin time, hemolytic anemia. Individual cases of agranulocytosis (<500 cells / μl) are described, most of them developing after 10 days of treatment and using a cumulative dose of 20 g or more.

Immune system disorders: anaphylactic shock, hypersensitivity.

Disturbances from the skin and subcutaneous tissues: acute generalized exanthematous pustulosis, isolated cases of severe adverse reactions (exudative erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome)).

Impaired nervous system: convulsions.

Hearing disorders and labyrinthine disturbances: Vertigo.

Infectious and parasitic diseases: superinfection.

The following undesirable reactions are also known: formation of precipitates of calcium salts of ceftriaxone in the gallbladder with the corresponding symptoms, bilirubin encephalopathy, hyperbilirubinemia, oliguria, vaginitis, increased sweating, "hot flashes", allergic pneumonitis, epistaxis, jaundice, palpitation, serum sickness, as well as anaphylactic or anaphylactoid reactions. Some fatal cases of precipitates formation in the lungs and kidneys have been described based on the results of an autopsy study in newborns receiving ceftriaxone and calcium-containing solutions. In some cases, one venous access was used, and the formation of precipitates was observed directly in the system for intravenous administration. Also, at least one fatal case with different venous accesses and at different times of administration of ceftriaxone and calcium-containing solutions is described. At the same time, according to the results of the study of autopsy in this newborn, the precipitates were notdetected. Similar cases were observed only in newborns (see section "Special instructions"). Cases of formation of ceftriaxone precipitates in the urinary tract were recorded, mainly in children receiving either large daily doses of the drug (≥80 mg / kg per day) or cumulative doses greater than 10 grams, and those who had additional risk factors (dehydration, bed rest) . The formation of precipitates in the kidneys can be asymptomatic or manifest clinically, can lead to ureteral obstruction and postrenal acute renal failure. This undesirable phenomenon is reversible and disappears after cessation of ceftriaxone therapy.

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

Intramuscular injection without the use of lidocaine painful.

Effect on the results of laboratory tests

In the treatment of ceftriaxone, false positive results of Coombs test may be noted in patients. Like other antibiotics, ceftriaxone can give a false positive test result for galactosemia. False positive results can also be obtained in the determination of glucose in the urine by non-enzyme methods, so in the course of ceftriaxone therapy, glucosuria, if necessary, should be determined only by the enzyme method.

Ceftriaxone may cause an unreliable decrease in the glycemic index obtained with some blood glucose monitoring devices. Refer to the instruction manual for the device you are using. If necessary, alternative methods for determining blood glucose should be used.

Overdose:

Symptoms

Nausea, vomiting and diarrhea.

Treatment

In case of an overdose, hemodialysis and peritoneal dialysis will not reduce the concentration of the drug. There is no specific antidote. Treatment of an overdose is symptomatic.

Interaction:

With the simultaneous use of large doses of the drug Ceftriaxone and "loop" diuretics (for example, furosemide), renal dysfunction was not observed. There are conflicting data on the likelihood of increased nephrotoxicity of aminoglycosides when used with cephalosporins,therefore, it is necessary to monitor renal function and concentration of aminoglycosides in the blood. Alcohol consumption after drug administration Ceftriaxone was not accompanied by a disulfiram-like reaction. Ceftriaxone does not contain an N-methylthiotetrazol group, which could cause ethanol intolerance and bleeding, which is inherent in some other cephalosporins. Probenecid does not affect the excretion of the drug Ceftriaxone.

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

In vitro, antagonism between chloramphenicol and ceftriaxone was detected. Do not use solvents containing calcium, such as Ringer's solution or Hartmann's solution, when preparing solutions of the drug Ceftriaxone for intravenous administration and their subsequent dilution due to the possible formation of precipitates.

The formation of precipitates of calcium salts of ceftriaxone can also occur when the preparation is mixed Ceftriaxone and calcium-containing solutions using a single venous access. Can not use Ceftriaxone 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 inject the drug Ceftriaxone and calcium-containing solutions with thorough washing of infusion systems between infusions of a compatible liquid. Two in vitro studies were conducted to evaluate the interaction of ceftriaxone and calcium: one with the use of adult blood plasma, the other with newborn cord blood plasma. Various combinations of ceftriaxone with an initial concentration of up to 1 mM were analyzed (the maximum concentration reached ceftriaxone in vivo with 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). A decrease in ceftriaxone concentration in plasma was observed with calcium at a concentration of 6 mM (24 mg / dl) and higher for adult plasma and at a concentration of 4 mM (16 mg / dl) and higher for neonatal plasma, indicating an increased risk of calcium salts formation ceftriaxone in newborns (see sections "Method of administration and dose", "Contraindications").

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

When vitamin K antagonists are used against the background of drug therapy Ceftriaxone increased risk of bleeding. It is necessary to constantly monitor the parameters of blood coagulation and, if necessary, adjust the dose of anticoagulant both during and after the end of therapy with the drug Ceftriaxone.

Synergy between ceftriaxone and aminoglycosides is shown for many gram-negative bacteria. Although the increased effectiveness of such combinations is not always predictable, it should be borne in mind in severe, life-threatening infections, such as conditional Pseudomonas aeruginosa.

Special instructions:

Hypersensitivity reactions

As with the use of other β-lactam antibiotics, severe hypersensitivity reactions, including fatalities, have been reported. With the development of severe hypersensitivity reactions, drug therapy Ceftriaxone it is necessary to immediately cancel and conduct appropriate emergency medical measures. Before starting therapy with the drug Ceftriaxone it is necessary to establish whether the patient has a hypersensitivity reaction to ceftriaxone, cephalosporins, or severe hypersensitivity reactions to other (3-lactam antibiotics (penicillins, monobactams and carbapenems).

Caution is advised when using ceftriaxone in patients with mild hypersensitivity reactions to other β-lactam antibiotics (penicillins, monobactams and carbapenems) in the anamnesis.

The sodium content

In 1 g of the preparation Ceftriaxone contains 3.6 mmol sodium. This should be taken into account for patients on a sodium-controlled diet.

Hemolytic anemia

As with the use of other cephalosporins, in the treatment of the drug Ceftriaxone possibly the development of autoimmune hemolytic anemia. Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported.

When developing anemia in a patient treated with ceftriaxone, one can not exclude the diagnosis of cephalosporin-associated anemia and it is necessary to cancel the treatment until the cause is clarified.

Diarrhea caused by Clostridium difficile

As with most other antibacterial drugs, with Ceftriaxone, cases of diarrhea caused by Clostridium difficile (C. difficile), different severity: from mild diarrhea to colitis with fatal outcome. Treatment with antibacterial drugs suppresses the normal microflora of the colon and provokes growth C. difficile. In its turn, C. difficile forms toxins A and B, which are factors in the pathogenesis of diarrhea caused by C. difficile. Strains C. difficile, hyper-producing toxins, are the causative agents of infections with a high risk of complications and mortality, due to their possible resistance to antimicrobial therapy, treatment may require colectomy. It is necessary to remember the possibility of developing diarrhea caused by C. difficile, in all patients with diarrhea after antibiotic therapy. It is necessary to carefully collect the anamnesis, tk. cases of diarrhea caused by C. difficile, more than 2 months after antibiotic therapy. If suspected or confirmed diarrhea caused by C. difficile, You may need to cancel the current not directed at C. difficile antibiotic therapy.In accordance with clinical indications, appropriate treatment should be prescribed with the introduction of fluid and electrolytes, proteins, antibiotic therapy in relation to C. difficile, surgical treatment. Do not use drugs that inhibit the intestinal motility.

Superinfections

As with other antibacterial drugs, superinfections can develop.

Changes in prothrombin time

Patients who received the drug Ceftriaxone, rare cases of prothrombin time change are described. Patients with vitamin K deficiency (impaired synthesis, eating disorder) 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 precipitates of calcium salt of ceftriaxone

Cases of fatal reactions as a result of deposition 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, including through separate access for infusion in various areas. Theoretically, based on the calculation of 5 periods of half-life of 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 preparations for oral administration, as well as ceftriaxone for intramuscular administration with calcium-containing drugs (intravenously or for oral administration) are not available. After applying ceftriaxone, usually at doses exceeding the standard recommended (1 g per day or more), ultrasound examination of the gallbladder revealed precipitates of calcium salt of ceftriaxone, the formation of which is most likely in children of childhood. Precipitates rarely give any symptoms and disappear after the completion or discontinuation of therapy with the drug Ceftriaxone. In the event that these phenomena are accompanied by clinical symptoms, conservative non-surgical treatment is recommended,and the decision on the abolition of the drug at the discretion of the treating physician and should be based on an individual assessment of benefit and risk. Despite the availability of data on the formation of intravascular precipitates only in newborns with the use of ceftriaxone and calcium-containing infusion solutions or any other calcium-containing drugs, the drug Ceftriaxone should not be mixed or prescribed to children and adults patients simultaneously with calcium-containing infusion solutions, even using different venous accesses (see the sections "Contraindications", "Interaction with other medicines").

Pancreatitis

Patients who received the drug Ceftriaxone, rare cases of pancreatitis, which developed, possibly, as a result of obstruction of the biliary tract, are described. Most of these patients already had risk factors for congestion in the biliary tract, for example, previous therapy, severe diseases and completely parenteral nutrition. At the same time, it is impossible to exclude the starting role in the development of pancreatitis formed under the influence of the drug Ceftriaxone precipitates in the biliary tract.

Use in children

Safety and efficacy of the drug Ceftriaxone in newborns, infants and young children were determined for the dosages described in the "Method of administration and dose" section. Studies have shown that, like other cephalosporins ceftriaxone can displace bilirubin from association with serum albumin. A drug Ceftriaxone Do not use in newborns, especially prematurity, who have a risk of developing bilirubin encephalopathy (see section "Contraindications").

Long-term treatment

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.

Monitoring of the blood test

With prolonged treatment, a full blood test should be performed regularly.

Serological tests

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).

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

There is no evidence of the effect of the drug on driving vehicles and working with machines and mechanisms.However, during drug therapy Ceftriaxone caution should be exercised when driving vehicles and operating machinery in connection with the possibility of dizziness and other undesirable reactions that may affect the ability to drive vehicles and mechanisms.

Form release / dosage:

Powder for solution for intravenous and intramuscular injection, 0.5 g and 1.0 g.

Packaging:

By 0.5 g or 1.0 g of ceftriaxone in glass bottles of type FF, FLP-10, 10R or 10Н, ukuporennye rubber stoppers and crimped aluminum caps.

1 or 10 vials, along with instructions for medical use, are placed in a pack of cardboard.

10 bottles together with the instruction for medical use are placed in a pack of cardboard with a cardboard insert for fixing the vials.

For hospitals: 50 or 270 vials, together with an equal number of instructions for medical use, are placed 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:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004146

Date of registration:14.02.2017

Expiration Date:14.02.2022

The owner of the registration certificate:BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Manufacturer: & nbsp

BORISOVSKIY FACTORY OF MEDPREPARATES, OJSC Republic of Belarus

Information update date: & nbsp25.03.2017

Illustrated instructions

Instructions

Ceftriaxone (Ceftriaxone)