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

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

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

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

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

Anaerobes

Bacteroidcs 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 of education lactamase.

Note. Many strains of β-lactamase-forming Bactеroidcs 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 established the following criteria for evaluation of the results of the sample for ceftriaxone:

Sensitive

Moderately

Steady sensitive

Method of dilution

The overwhelming concentration, mg / l

= 8

16-32

= 64

Disc method (disc with 30 μg ceftriaxone)

Diameter of the zone of growth retardation, mm

=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 for determining the sensitivity of microorganisms, it is possible to use other well-standardized standards, for example,German Institute for Standardization DIN (Deutsches Institut fur Normung) and international recommendations ICS (International Collaborative Study), allowing to 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 500 mg and 1 g of ceftriaxone, the mean maximum plasma concentration was 120 mg / L and 200 mg / L. respectively.After intravenous infusion of 500 mg, 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 concentration of ceftriaxone in the blood plasma is approximately two times lower than 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 pathogens 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 fluid , 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% of the plasma concentration in patients with non-inflamed cerebral membranes. 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 enters 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.The renal 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.

Impaired renal or hepatic function

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 the compensatory increase in chain clearance due to a decrease in the degree of binding to the proteins of the plasma of the croup and the corresponding increase in the non-obese clearance of total ceftriaxone.

In patients with hepatic insufficiency, the half-life does not increase. In such patients, there is a compensatory increase in renal 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, biliary tract infections and gastrointestinal tract) infections 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-old age)

- Hyperbilirubinemia, jaundice or acidosis, hypoalbuminemia in newborns (in vitro studies have shown that ceftriaxone can displace bilirubin from 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) who have already been prescribed or are expected to receive intravenous calcium-containing solutions, including long-term calcium-containing infusions, for example with parenteral nutrition, because of the risk of calcium precipitates formation of ceftriaxone (see "Dosage and administration" and "Interaction with other medicinal means "). Some fatal cases of the formation of precipitates in the lungs and kidneys in newborns receiving Rocefin® and calcium-containing solutions are described. 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 various venous accesses and at different times of administration of the preparation of Rocefin® and calcium-containing solutions was also described. 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:

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 baby who is breastfeeding when it is used by the mother at therapeutic doses, however,can not exclude the risk of diarrhea, fungal infections of the mucous membranes and hypersensitivity reactions in the child. 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 of age >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 Rocefin® should be continued for at least 48-72 hours after the temperature is normalized and the eradication of the pathogen is confirmed.

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

The general rule should be the use of solutions immediately after preparation. The prepared solutions retain their physical and chemical stability for 6 hours at room temperature (or for 24 hours at a temperature of 2-8 ° C). Depending on the concentration and duration of storage, the color of solutions can vary from pale yellow to amber. The color of the solution does not affect the efficacy or tolerability of the preparation.

For intramuscular injection 250 mg or 500 mg of the drug Rocefin ® is dissolved in 2 ml, a1 g - in 3.5 ml of a 1% solution of lidocaine and injected deep into a sufficiently large muscle (buttock). It is recommended to inject no more than 1 g into the same muscle. The solution containing lidocaine, can not be administered intravenously.

For intravenous injection Dissolve 250 mg or 500 mg of the drug Rocefin ® in 5 ml, and 1 g - in 10 ml of sterile water for injection; is administered intravenously slowly for 5 minutes, preferably in a large vein.

Intravenous infusion should last at least 30 minutes. To prepare the solution, 2 g of Rocefin® is dissolved 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% solution of hydroxyethyl starch, water for injections. Solutions of the preparation Rocefin® can not mixed or added to solutions containing other antimicrobial agents or other solvents, with the exception of those listed above, because of the possible incompatibility.

It can not be used for preparing drug solutions for intravenous administration Rotsefin® and their subsequent dilution solvents containing calcium, such as Ringer's solution or Hartman's solution, because of the possible formation of precipitates. The formation of calcium salt precipitates ceftriaxone may occur by mixing the drug Rotsefin® and calcium solutions using a venous access. Rotsefin® can not be used simultaneously with the calcium-containing solutions for intravenous administration, including continuous infusion of solutions of calcium, for example, parenteral nutrition using a Y-connector. For all patients groups except infants may Rotsefin® sequential administration of the drug and calcium solutions with thorough washing with infusion systemsbetween infusions of a compatible liquid (see section "Interaction with other drugs").

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. The daily dose of the drug Rocefin® should not exceed 2 g only in cases of renal failure with a creatinine clearance less than 10 ml / min. Ceftriaxone is not excreted in hemodialysis or peritoneal dialysis, therefore, the patient is not required to administer an additional dose of Rocefin® after the end of dialysis.

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 appointing the drug Rocefin ® 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. Rocefin® is contraindicated in newborns (<28 days) who have already been prescribed or are expected to receive intravenous calcium-containing solutions, including long-term calcium-containing infusions, for example, with parenteral nutrition due to the risk of calcium precipitates formation of ceftriaxone (see "Contraindications" section)

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 penicillin-forming and penicillin-zoned strains)

Single intramuscular injection of 250 mg of Rocefin® to adult patients and children over 12 years of age >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 Rocefin® 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 Rocefin® is administered once for 30-90 min before the operation. In operations on the colon and rectum, the administration of the preparation Rocefin® and one of the 5-nitroimidazoles, for example, ornidazole, has proved to be simultaneous (but separate, see the section "Dosing and Administration").

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), the 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 stools; infrequently - nausea, vomiting.

Disorders from the liver and urinary tract: 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. increased body temperature: rarely - edema, chills.

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

Post-Business Monitoring

Below are described the side effects observed with the use of the drug Rocefin® in the post-marketing period. The frequency of the observed side effects, as well as their association with the use of the drug Rocefin®, 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 of the 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.

Individual fatal cases of precipitates formation in the lungs and kidneys are described according to the results of the autopsy study in newborns receiving Rocefin® 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 the preparation of Rocefin® 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 / day), or cumulative doses of more than 10 g, as well as 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 discontinuation of therapy with Rocefin®.

Common disorders and disorders together: 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

When treated with Rocefin®, patients may experience false positive results from Coombs.Like other antibiotics, the preparation of Rocefin® can give a false positive test result for galactosemia. False positive results can be obtained in the determination of glucose in urine by non-enzyme methods, therefore, during therapy with the preparation of Rocefin® glucosuria, if necessary, it is necessary to determine 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 Rocefin® and looped diuretics (eg, 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. The use of alcohol after the administration of the drug Rocefin® 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 Rocefin®.

Bacteriostatic antibiotics reduce the bactericidal effect of ceftriaxone.

In vitro, antagonism between chloramphenicol and ceftriaxone was detected. Can not be used, solvents containing calcium, such as Ringer's solution or Hartmann's solution, in the preparation of solutions of the preparation of Rocefin® 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 mixing the preparation of Rocefina® and calcium-containing solutions using a single venous access. Do not use Rocefin® concomitantly with calcium-containing solutions for intravenous administration,including those with long infusions of calcium-containing solutions, for example, with parenteral nutrition using a Y-connector. For all groups of patients, except for newborns, it is possible to consistently administer the preparation of Rocefin® and calcium-containing solutions with thorough washing of the 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.sections "Dosing and Administration", "Contraindications").

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

With the use of vitamin K antagonists, the risk of bleeding increases with the use of Rocefin®. It is necessary to constantly monitor the parameters of blood coagulation and, if necessary, adjust the dose of anticoagulant both during and after the termination of therapy with Rocefin®.

Synergy between ceftriaxone and aminoglycosides is shown for many gram-negative bacteria. Although the increased efficacy of such combinations is not always predictable, it should be borne in mind in severe, life-threatening infections, such as those caused by 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 a severe hypersensitivity reaction, therapy with Rocefin® should be immediately canceled and appropriate emergency medical interventions performed.Before starting therapy with Rocefin®, it is necessary to establish whether the patient has a hypersensitivity reaction to ceftriaxone, cephalosporins, or severe hypersensitivity reactions to other β-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 product, Rocefin® contains 3.6 mmol of sodium. This should be taken into account for patients on a sodium-controlled diet.

Hemolytic anemia

As with the use of other cephalosporins, the development of autoimmune hemolytic anemia is possible with the treatment with Rocefin®. Cases of severe hemolytic anemia in adults and children, including fatal cases, have been reported. With the development of anemia in a patient treated with ceftriaxone, anemia can not be excluded from 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, cases of diarrhea caused by ceftriaxone Clostridium difficile (C. difficile), varying severity: from mild diarrhea to colitis and fatal. Treatment with antibacterial drugs suppresses the normal microflora of the large intestine and provokes growth of 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 you suspect or confirm 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, surgery. Do not use drugs that inhibit the intestinal motility.

FROMureinfection

As with other antibacterial drugs, superinfections can develop.

Changes in prothrombin time

Patients treated with Rocefin® reported rare cases of prothrombin time change. 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 injection with calcium-containing drugs (intravenously or for oral administration reception) are absent. After the application of ceftriaxone, precipitates of the calcium salt of ceftriaxone, whose formation is most likely in pediatric patients, were usually detected at doses exceeding the standard recommended (1 g per day or more) with ultrasound examination of the gallbladder. Precipitates rarely give any symptomatology and disappear after the completion or discontinuation of therapy with Rocefin®. In the event that the phenomena are accompanied by clinical symptoms, conservative non-surgical treatment is recommended,and the decision to cancel the drug is left to the discretion of the attending physician and should be based on an individual assessment of the benefits and risks.

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 Rocefin® preparation should not be mixed or administered to children and adult patients concomitantly with calcium-containing infusion solutions, even using different venous accesses. sections "Contraindications." "Interaction with other medicines", subsection "Post-registration surveillance").

Pancreatitis

Patients receiving the preparation of Rocefin® described rare cases of pancreatitis, which developed, possibly, as a result of obstruction of the biliary tract. Most of them already had risk factors for congestion in the biliary tract, for example, previous therapy, severe illnesses and completely parenteral nutrition. At the same time, it is impossible to exclude the starting role in the development of pancreatitis caused by the preparation Rocefin® precipitates in the biliary tract.

Use in children

The safety and efficacy of the drug Rocefin® in newborns, infants and young children have been determined for the dosages described in the section "Dosing and Administration". Studies have shown that, like other cephalosporins ceftriaxone can displace bilirubin from association with serum albumin. The drug Rocefin® should not be used in newborns, especially premature babies, who are at risk for developing bilirubin encephalopathy (see "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 therapy with Rocefin®, caution should be exercised when driving vehicles and handling machinery due to 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 1 g.

Packaging:

Powder for solution for intramuscular injection 250 mg, 500 mg, 1 g.

Set:

For 250 mg, 500 mg or 1 g of ceftriaxone in a glass bottle (glass hydrolytic class 1 EF), sealed with a butyl rubber stopper, crimped with an aluminum cap and closed with a plastic lid.

2 ml (for a preparation of Rocefin® 250 mg and 500 mg) or 3.5 ml (for the preparation Rocefin® 1 g) of 1% lidocaine solution in ampoules made of glass of hydrolytic class 1 EF, sealed according to ISO 9187 sealed. On the ampoule with the solvent there is a blue dot: on the tip of the ampoule there are two rings of blue and green. 1 bottle with the drug together with 1 ampoule of lidocaine 1% solution and the instructions for use are placed in a cardboard box.

Powder for the preparation of a solution for intravenous administration of 250 mg, 500 mg, 1 g.

Set:

For 250 mg, 500 mg or 1 g of ceftriaxone in a glass bottle (glass hydrolytic class 1 EF), sealed with a butyl rubber stopper, crimped with an aluminum cap and covered with a plastic lid.

5 ml (for the preparation Rocefin® 250 mg and 500 mg) or 10 ml (for the preparation Rocefin® 1 g) of water for injection into ampoules made of glass of hydrolytic class 1 EF, sealed according to ISO 9187. The ampoule has a blue dot.

1 bottle with the drug together with 1 ampoule of water for injection and instructions for use are placed in a cardboard box.

Powder for solution for infusion 2 g

2 g of ceftriaxone in a glass vial (hydrolytic class 1 EF glass), sealed with a butyl rubber stopper, crimped with an aluminum cap and covered with a plastic lid.

1 bottle together with the instruction for use is placed in a cardboard box.

Powder for solution for intravenous and intramuscular administration 1 g

1 g of ceftriaxone in a glass bottle (hydrolytic class 1 EF glass), sealed with a plug of butyl rubber,Crimped with an aluminum cap and closed with a plastic cover.

1 bottle together with the instruction for use is placed in a cardboard box.

For hospitals: For 143 vials together with the appropriate number of instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 30 ° C in a dark place. Keep out of the reach of children.

The prepared solution should be stored at room temperature for no more than 6 hours or in the refrigerator at 2-8 ° C for not more than 24 hours.

Shelf life:

3 years.

The drug should not be used but the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013244 / 04

Date of registration:27.08.2010

Expiration Date:Unlimited

The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland

Manufacturer: & nbsp

F.Hoffmann-La Roche, Ltd. Switzerland

CENEXI, SAS France

Representation: & nbspROSH-MOSCOW, CJSCROSH-MOSCOW, CJSCRussia

Information update date: & nbsp21.11.2017

Illustrated instructions

Instructions

Rocefin® (Rocephin®)